Here's a picture we took on the last evening of 2010, looking forward to 2011.
Friday, December 31, 2010
Happy New Year
One of my favorite Copland pieces is the second movement from Rodeo - the Corral Nocturne (right click in new tab to play). It's on most of my lullaby playlists, and is modern and sweet without being precious. It is also quite brief at a little over three and a half minutes, so lean back, close your eyes, and sit a spell, if you do that sort of thing. I find many people can't unwind, can't unfold. Corral Nocturne might help if you are in that predicament. Orchestral music may not be terribly old, but it sure does speak to something within us.
Here's a picture we took on the last evening of 2010, looking forward to 2011.
Here's a picture we took on the last evening of 2010, looking forward to 2011.
Closing Out 2010
For many, like my beloved Texas Longhorns, 2010 was a difficult year. I started the year in a plateau, having gained and lost (and gained and lost) quite a few pounds during and after pregnancies for my two little girls. Nutrition was an interest of mine for many years, however. I had read Good Calories, Bad Calories and the works of Micheal Pollan, and for years had been avoiding too much fake processed food and vegetable oil. But it wasn't until I found the idea of a paleolithic-style diet that everything began to have focus, and made perfect sense. I started out with a nutritionist who had a paleolithic bent (but a distaste of fat and a fondness for brown rice and oatmeal nonetheless). I would describe his plan as Loren Cordain meets Body For Life. I followed his plan for 3 months, losing all the excess baby weight and then some, then discovered The Primal Blueprint, where paleo meets Good Calories, Bad Calories, and Food and Western Disease (paleo meets academia). I added back the fat, ditched the post-workout brown rice and oatmeal, and through a perusal of the forums found the wonderful resources of the paleo and traditional foods blogs, and the rest is history.
None of that had much to do with psychiatry. But with my biochemistry knowledge and front lines experience with mental illness, it seemed an obvious route to take with a blog. As a population, we are long-lived and expensive and sick. It didn't seem to me that hunter-gatherers could have been so afflicted and survive very long. And many of my patients (and myself) had the look - the extra pounds, the flushed skin, the thin hair - something was wrong. Very wrong.
It is not that hard to find inflammation. A new commenter on an older post noted that it seems to be in fashion to blame everything on inflammation. And to some extent I agree - when I was pregnant, all the little discomforts (loose joints, weight gain, bleeding gums) were blamed on "hormones." Inflammation is a big word, covering a vast landscape of biochemical processes. But it is a place to start, beyond psychology, beyond stress. Inflammation is where vegetable oil meets the modern stressful life. And that is where psychopathology lies as well.
There are a number of ways to attack psychopathology. Therapy, exercise, proper sleep and avoidance of addictive poisons. And here I focus on food, and parse the details. This is science so the definitive is less than we would like. But this is science, so we can question dogma.
Fortunately, I have all my friends to parse with me. And that is the greatest blessing from 2010. Not the skinny jeans, the clear skin, or the vibrant hair (though those are quite nice). The greatest blessing is the community. My old friend Dan from medical school, gorgeous Jamie and Julianne all the way in New Zealand. Stephan in the northwest US, Dr. BG and Aaron Blaisdell insouthern California. Steve Parker in Arizona. Paul Jaminet a few miles away in Cambridge. Melissa in NYC. Thanks to Leslie Irish Evans and Robert Su for the podcast opportunities! Andrew on his boat. Enigmatic paleo rock star Kurt Harris in the midwest. Dr. Eades and Richard Nikoley. The commenters and facebook friends and twitter community who are all ready to look at a new angle and take apart a new or old idea. Tear it apart. That's what leads us forward.
Evolutionary medicine in the 21st century is a breathtaking enterprise. I can be a doctor and use my powers for good. My plans for the blog include (yes, at long last) the thyroid, delving more into phospholipids and the now-famous choline, and looking more into sleep. I'll endeavor along the way to keep up with the latest news and papers (though I still have a day job, a husband, and two adorable little girls). I'm looking forward to a gluten-free January, and more pairs of skinny jeans. Mostly I follow the winds, and my nose, and my gut, which I suppose is more or less what my ancestors did.
It is nice to be able to use one's powers for good. Happy New Year.
None of that had much to do with psychiatry. But with my biochemistry knowledge and front lines experience with mental illness, it seemed an obvious route to take with a blog. As a population, we are long-lived and expensive and sick. It didn't seem to me that hunter-gatherers could have been so afflicted and survive very long. And many of my patients (and myself) had the look - the extra pounds, the flushed skin, the thin hair - something was wrong. Very wrong.
It is not that hard to find inflammation. A new commenter on an older post noted that it seems to be in fashion to blame everything on inflammation. And to some extent I agree - when I was pregnant, all the little discomforts (loose joints, weight gain, bleeding gums) were blamed on "hormones." Inflammation is a big word, covering a vast landscape of biochemical processes. But it is a place to start, beyond psychology, beyond stress. Inflammation is where vegetable oil meets the modern stressful life. And that is where psychopathology lies as well.
There are a number of ways to attack psychopathology. Therapy, exercise, proper sleep and avoidance of addictive poisons. And here I focus on food, and parse the details. This is science so the definitive is less than we would like. But this is science, so we can question dogma.
Fortunately, I have all my friends to parse with me. And that is the greatest blessing from 2010. Not the skinny jeans, the clear skin, or the vibrant hair (though those are quite nice). The greatest blessing is the community. My old friend Dan from medical school, gorgeous Jamie and Julianne all the way in New Zealand. Stephan in the northwest US, Dr. BG and Aaron Blaisdell in
Evolutionary medicine in the 21st century is a breathtaking enterprise. I can be a doctor and use my powers for good. My plans for the blog include (yes, at long last) the thyroid, delving more into phospholipids and the now-famous choline, and looking more into sleep. I'll endeavor along the way to keep up with the latest news and papers (though I still have a day job, a husband, and two adorable little girls). I'm looking forward to a gluten-free January, and more pairs of skinny jeans. Mostly I follow the winds, and my nose, and my gut, which I suppose is more or less what my ancestors did.
It is nice to be able to use one's powers for good. Happy New Year.
Thursday, December 30, 2010
Parasites Can Be Transmitted By Pet Dog
Many animals can make our pets such as cats, dogs, rabbits, birds and reptiles like snakes. Dogs are one of the beasts that dwell among the animals around our house. It is sometimes so sweet, so we wanted to pet him or hug him. Dogs are domesticated very popular because it can be friendly with us as their masters and also because of intelligence and instinct can be used as a reliable keeper's house. But like other animals that transmit the parasite that dogs can endanger human health.
Of the approximately 200 types of zoonotic or parasites that are transmitted by animals, is actually not all can be transmitted by dogs to humans. Some of the deadly infectious diseases in dogs such as distemper, parvovirus, and heartworms will not be transmitted to humans.
But some other parasite species to watch out, because dogs can transmit to humans. Here are some types of disease that is transmitted through dogs.
1. Rabies
Rabies is an acute infection of the central nervous system caused by rabies virus Lyssavirus which up to now there is no cure. However, the virus can still be prevented with anti-rabies vaccine for distribution does not reach the brain.
Where has reached the brain, the virus can paralyze some organ systems primarily associated with breathing. At this stage called Lyssa, the patient will experience severe shortness of breath and eventually died horribly a few hours later.
2. Campylobacteriosis
Diseases that attack perncernaan channel is caused by bacteria campylobacter jejuni. The bacteria are transmitted by domestic animals including dogs, cats and birds through direct contact, contamination of drinking water and consumption of meat is not overcooked.
Symptoms that appear on campylobacteriosis are diarrhea, stomach pain and at a certain level of severity can cause high fever. If diarrhea is not resolved, the worst risk is dehydration or loss of body fluids.
3. Skin disease
Types of skin disease that is often transmitted by dogs is dermatophytosis or ringworm characterized by itchy patches on the skin with a circular pattern. The cause is a fungus that spreads through direct contact with the skin surface of infected dogs.
Other skin diseases that are transmitted by dogs are scabies caused by fleas. This bug can sneak into the bottom surface of the skin and cause a red rash, scaly skin on the head until the hair loss and other skin surfaces.
4. Toxocariasis
Diseases caused by Toxocara canis worm infections occurred in the digestive tract of dogs and their eggs can be carried by the feces and then contaminate the soil. If inhaled or ingested by humans, the eggs will hatch in the stomach and then migrate to other body tissues.
In skin tissue, the larvae of this worm will only lead to minor complaints such as rashes and itching although sometimes accompanied by fever, cough and swollen lymph glands. Although rare, this worm larvae can also reach the hearts and eyes and cause disturbances in the function of these organs.
Of the approximately 200 types of zoonotic or parasites that are transmitted by animals, is actually not all can be transmitted by dogs to humans. Some of the deadly infectious diseases in dogs such as distemper, parvovirus, and heartworms will not be transmitted to humans.
But some other parasite species to watch out, because dogs can transmit to humans. Here are some types of disease that is transmitted through dogs.
1. Rabies
Rabies is an acute infection of the central nervous system caused by rabies virus Lyssavirus which up to now there is no cure. However, the virus can still be prevented with anti-rabies vaccine for distribution does not reach the brain.
Where has reached the brain, the virus can paralyze some organ systems primarily associated with breathing. At this stage called Lyssa, the patient will experience severe shortness of breath and eventually died horribly a few hours later.
2. Campylobacteriosis
Diseases that attack perncernaan channel is caused by bacteria campylobacter jejuni. The bacteria are transmitted by domestic animals including dogs, cats and birds through direct contact, contamination of drinking water and consumption of meat is not overcooked.
Symptoms that appear on campylobacteriosis are diarrhea, stomach pain and at a certain level of severity can cause high fever. If diarrhea is not resolved, the worst risk is dehydration or loss of body fluids.
3. Skin disease
Types of skin disease that is often transmitted by dogs is dermatophytosis or ringworm characterized by itchy patches on the skin with a circular pattern. The cause is a fungus that spreads through direct contact with the skin surface of infected dogs.
Other skin diseases that are transmitted by dogs are scabies caused by fleas. This bug can sneak into the bottom surface of the skin and cause a red rash, scaly skin on the head until the hair loss and other skin surfaces.
4. Toxocariasis
Diseases caused by Toxocara canis worm infections occurred in the digestive tract of dogs and their eggs can be carried by the feces and then contaminate the soil. If inhaled or ingested by humans, the eggs will hatch in the stomach and then migrate to other body tissues.
In skin tissue, the larvae of this worm will only lead to minor complaints such as rashes and itching although sometimes accompanied by fever, cough and swollen lymph glands. Although rare, this worm larvae can also reach the hearts and eyes and cause disturbances in the function of these organs.
Tips for controlling your blood sugar level in Diabetes.
Diabetic persons should be more careful about their blood sugar level known as glucose. Therefore it is necessary to know how can you control the sugar level in blood and what can be causes for increase.Here are the caused, which can increase your blood sugar level:1.Eating too much and unhealthy diet will lead an increase in the blood sugar level. You may fall sick when this increases.2.If
Wednesday, December 29, 2010
Your Brain On Creatine
Thank you, good paleo fairy, Melissa McEwan. By my count, next time I'm in NYC I owe you a half dozen NorCal Margaritas. And thank you also former primal muse who has now moved over to That Paleo Guy (I should just send you a margarita machine.) I now have in my little hands several creatine fed to vegetarians papers (1)(2)(3). Seems that cognition researchers (and athletic performance researchers) simply love giving vegetarians creatine - a practice that might seem curious until you look at these facts:
1) Creatine is an amino acid found only in animal flesh but most abundantly in skeletal muscle flesh (like steak). It is not an essential amino acid, as we can synthesize is from other amino acids found also in plant foods, but as with changing the plant-based omega 3 fatty acid ALA to the marine animal based omega 3 acid DHA, the synthesis is inefficient. It is known that vegetarians have lower tissue (measured directly via muscle biopsy) amounts of creatine than omnivores (4).
2) Why should we care if we have creatine? Well, if you recall, our cells run on energy supplied by ATP. Whether we fuel up with glucose or ketones, eventually those raw materials get transformed into ATP, which as it is broken down powers all sorts of energy-requiring processes. We will obviously burn through ATP faster in our muscles when we are running or jumping or performing various feats of strength, but we also burn through ATP faster when we are using our noggins for something a bit complicated. Our little brain (the size of your two fists held together) burns through 20% of the energy we use each day, primarily to keep those ion gradients fueled that allow our neurons to charge up and then be discharged to communicate information.
3) Creatine can bind to phosphate (P) to make phosphocreatine, and this acts as a "buffer" to make ATP lickety-split. Turns out we can make ATP 12 times faster using phosphate reserves from phosphocreatine than by using oxidative phosphorylation and a whopping 70 times faster than making ATP de novo. When we think hard, brain levels of phosphocreatine can drop pretty acutely while ATP levels stay constant, showing that we can bust into that reserve to keep our thinking sharp. In short, creatine improves brain efficiency.
So let's look at these papers, shall we? In both the cognition study papers, healthy college students were recruited (colleges being both a good source of research volunteers and vegetarians) and divided into creatine or placebo supplementation groups. The British study compared vegetarians and vegan young women to omnivores, the Australian study used only vegetarians and vegans, but had a crossover design (all subjects got both placebo and creatine along the way). Both studies did various measures of cognitive and memory testing (number of words you can remember from a list read to you, how many F or P words you can say in 2 minutes, how many numbers you can repeat backwards from a string of numbers read to you, recognizing strings of three even or odd numbers in a series of numbers read at 100 per second). The British study added a measure of reaction time (subjects had to press a button corresponding to a light as fast as they could once it was lit). The Australian study was 6 weeks, the British study was 5 days, and both used 5g creatine monohydrate as the supplement and dextrose (glucose) as the control.
Because glucose administration has been shown to (immediately) increase cognitive performance (5), all the cognitive testing was done fasted and on a day with no supplementation.
The results? First off, everyone, vegetarian or omnivore, on placebo or creatine in the British study did worse the second time around on the memory tests (maybe they got bored?). But compared to the placebo group, the omnivores in the British study were about the same as the creatine supplement group (omnivores have been shown to benefit from a maximum of 20 grams a day at first then maintenance 2-5 grams per day supplementing for athletic performance), suggesting that us animal flesh eaters have a physiologically appropriate amount of phophocreatine reserve in the brain for interesting tasks such as pushing buttons in response to light stimuli and complicated mental tasks that involve the prefrontal cortex and the hippocampus.
The vegetarians in the creatine group did much better than the vegetarians in the placebo group on the second battery of tests involving word recall and measures of variability of reaction times. More simple mental tasks didn't improve in the vegetarians or the omnivores, suggesting, interestingly enough, that complicated thinking burns more energy than uncomplicated thinking (so do smart people burn more calories?? I'm not aware of any research to that effect, in fact I thought there wasn't much of a difference, but we'll look into it...). In some of the measures, vegetarians were higher than omnivores at baseline, by the way, and in general the memory tests between the two groups did not vary at baseline - the vegetarians just seemed to benefit much more from creatine supplementation.
In the Australian study (using only vegans and vegetarians), creatine supplementation had a significant positive effect on working memory (using backwards digit span) and intelligence measures requiring processing speed. Various cognitive tasks that were worse in the placebo vegetarians compared to creatine vegetarians are similar to those that are affected in ADHD, schizophrenia, dementia, and traumatic brain injury. In addition, people with the Apoe4 allele and therefore more vulnerable to developing Alzheimer's seem to have lower brain levels of creatine.
There. Simple - when we are not being simple, we do better with creatine.
Except there are a few wee wrinkles. It turns out that creatine supplementation seems to have an effect on glucose regulation (3)(6). Weirdly, the first study shows a higher glucose level to a oral glucose tolerance load (in vegetarians), and the second study (in young athletically active males) shows a lower amount of area under the oral glucose tolerance test curve (that's good - shows increased glycemic control) with creatine supplementation. But if we consider the fact that a ready supply of glucose in the short term can improve cognitive performance, the British investigators were wondering if creatine supplementation increased glucose in vegetarians, thus increasing cognitive performance. They didn't bother to measure the glucose in the subjects, though, so who knows. In the Australian study, glucose was measured in the fasting subjects but specific levels were not reported in the paper, but it didn't seem that anyone had a high level.
In addition, creatine in the tissue doesn't necessarily equal creatine in the brain - however, animal studies have shown that problems with the creatine transporter into the brain shows up as cognitive problems similar to the unsupplemented human vegetarians (compared to their supplemented vegetarian brethren). However, it is likely that the synthesis and transport mechanisms are upregulated in vegetarians (as they have low levels of creatine), so creatine might pack more punch early on for the veggies, until levels become saturated.
Well, I'm not all that interested in supplementing with creatine. But I am interested in continuing to eat steak, and in having the most efficient energy reserves available for my brain.
And another question - if low levels of creatine can contribute to Parkinson's, are vegetarians more vulnerable to Parkinson's? I'm not sure of the provenance of this very interesting document I found on the internet - but it seems to be written by vegetarian physician and advocate Joel Furhman (though his suggested food pyramid does allow for animal products at the small tippy top) about two case studies of vegans developing Parkinson's, blaming low levels of DHA, and Dr. Furhman then peddling his vegan DHA product. But maybe creatine deficiency could be implicated? Who knows? I'll be eating plenty of meat just to be safe.
1) Creatine is an amino acid found only in animal flesh but most abundantly in skeletal muscle flesh (like steak). It is not an essential amino acid, as we can synthesize is from other amino acids found also in plant foods, but as with changing the plant-based omega 3 fatty acid ALA to the marine animal based omega 3 acid DHA, the synthesis is inefficient. It is known that vegetarians have lower tissue (measured directly via muscle biopsy) amounts of creatine than omnivores (4).
2) Why should we care if we have creatine? Well, if you recall, our cells run on energy supplied by ATP. Whether we fuel up with glucose or ketones, eventually those raw materials get transformed into ATP, which as it is broken down powers all sorts of energy-requiring processes. We will obviously burn through ATP faster in our muscles when we are running or jumping or performing various feats of strength, but we also burn through ATP faster when we are using our noggins for something a bit complicated. Our little brain (the size of your two fists held together) burns through 20% of the energy we use each day, primarily to keep those ion gradients fueled that allow our neurons to charge up and then be discharged to communicate information.
3) Creatine can bind to phosphate (P) to make phosphocreatine, and this acts as a "buffer" to make ATP lickety-split. Turns out we can make ATP 12 times faster using phosphate reserves from phosphocreatine than by using oxidative phosphorylation and a whopping 70 times faster than making ATP de novo. When we think hard, brain levels of phosphocreatine can drop pretty acutely while ATP levels stay constant, showing that we can bust into that reserve to keep our thinking sharp. In short, creatine improves brain efficiency.
So let's look at these papers, shall we? In both the cognition study papers, healthy college students were recruited (colleges being both a good source of research volunteers and vegetarians) and divided into creatine or placebo supplementation groups. The British study compared vegetarians and vegan young women to omnivores, the Australian study used only vegetarians and vegans, but had a crossover design (all subjects got both placebo and creatine along the way). Both studies did various measures of cognitive and memory testing (number of words you can remember from a list read to you, how many F or P words you can say in 2 minutes, how many numbers you can repeat backwards from a string of numbers read to you, recognizing strings of three even or odd numbers in a series of numbers read at 100 per second). The British study added a measure of reaction time (subjects had to press a button corresponding to a light as fast as they could once it was lit). The Australian study was 6 weeks, the British study was 5 days, and both used 5g creatine monohydrate as the supplement and dextrose (glucose) as the control.
Because glucose administration has been shown to (immediately) increase cognitive performance (5), all the cognitive testing was done fasted and on a day with no supplementation.
The results? First off, everyone, vegetarian or omnivore, on placebo or creatine in the British study did worse the second time around on the memory tests (maybe they got bored?). But compared to the placebo group, the omnivores in the British study were about the same as the creatine supplement group (omnivores have been shown to benefit from a maximum of 20 grams a day at first then maintenance 2-5 grams per day supplementing for athletic performance), suggesting that us animal flesh eaters have a physiologically appropriate amount of phophocreatine reserve in the brain for interesting tasks such as pushing buttons in response to light stimuli and complicated mental tasks that involve the prefrontal cortex and the hippocampus.
The vegetarians in the creatine group did much better than the vegetarians in the placebo group on the second battery of tests involving word recall and measures of variability of reaction times. More simple mental tasks didn't improve in the vegetarians or the omnivores, suggesting, interestingly enough, that complicated thinking burns more energy than uncomplicated thinking (so do smart people burn more calories?? I'm not aware of any research to that effect, in fact I thought there wasn't much of a difference, but we'll look into it...). In some of the measures, vegetarians were higher than omnivores at baseline, by the way, and in general the memory tests between the two groups did not vary at baseline - the vegetarians just seemed to benefit much more from creatine supplementation.
In the Australian study (using only vegans and vegetarians), creatine supplementation had a significant positive effect on working memory (using backwards digit span) and intelligence measures requiring processing speed. Various cognitive tasks that were worse in the placebo vegetarians compared to creatine vegetarians are similar to those that are affected in ADHD, schizophrenia, dementia, and traumatic brain injury. In addition, people with the Apoe4 allele and therefore more vulnerable to developing Alzheimer's seem to have lower brain levels of creatine.
There. Simple - when we are not being simple, we do better with creatine.
Except there are a few wee wrinkles. It turns out that creatine supplementation seems to have an effect on glucose regulation (3)(6). Weirdly, the first study shows a higher glucose level to a oral glucose tolerance load (in vegetarians), and the second study (in young athletically active males) shows a lower amount of area under the oral glucose tolerance test curve (that's good - shows increased glycemic control) with creatine supplementation. But if we consider the fact that a ready supply of glucose in the short term can improve cognitive performance, the British investigators were wondering if creatine supplementation increased glucose in vegetarians, thus increasing cognitive performance. They didn't bother to measure the glucose in the subjects, though, so who knows. In the Australian study, glucose was measured in the fasting subjects but specific levels were not reported in the paper, but it didn't seem that anyone had a high level.
In addition, creatine in the tissue doesn't necessarily equal creatine in the brain - however, animal studies have shown that problems with the creatine transporter into the brain shows up as cognitive problems similar to the unsupplemented human vegetarians (compared to their supplemented vegetarian brethren). However, it is likely that the synthesis and transport mechanisms are upregulated in vegetarians (as they have low levels of creatine), so creatine might pack more punch early on for the veggies, until levels become saturated.
Well, I'm not all that interested in supplementing with creatine. But I am interested in continuing to eat steak, and in having the most efficient energy reserves available for my brain.
And another question - if low levels of creatine can contribute to Parkinson's, are vegetarians more vulnerable to Parkinson's? I'm not sure of the provenance of this very interesting document I found on the internet - but it seems to be written by vegetarian physician and advocate Joel Furhman (though his suggested food pyramid does allow for animal products at the small tippy top) about two case studies of vegans developing Parkinson's, blaming low levels of DHA, and Dr. Furhman then peddling his vegan DHA product. But maybe creatine deficiency could be implicated? Who knows? I'll be eating plenty of meat just to be safe.
Tuesday, December 28, 2010
Control blood sugar level with Avandia.
Avandia is an anti diabetic agent. It helps the body to respond well to insulin and reduces the amount of sugar which is produced by the liver. It aids to control blood sugar levels. This medicine is effective with proper diet and exercise for treatment of type 2 diabetes. Rosiglitazone is the generic name of Avandia and it is an oral type of medication. Though it treats diabetes it is most
The Vulnerable Substantia Nigra
Blogging while out of town has proved more difficult that I thought. For one thing, we have free babysitting, so we've obviously been going out at night rather than staying in. Also, I am mostly limited to the iPad, which isn't as easy to blog from as a normal computer (yes, cry me a river, but true nonetheless). And I was planning on blogging about the creatine and vegetarians paper from the British Journal of Nutrition. However, It turns out my institution doesn't have access to the full text, and I really don't want to shell out $45 for a single paper that tells me to eat meat. I already eat meat, and if you want your brain to be tip top, probably best you do too, or supplement, supplement, supplement with that growing list (B12, zinc, taurine, creatine, carnosine, etc. etc.)
But anyway. A few weeks ago, Dr. Aaron Blaisdell, who I'm told will have access to all the best parties at the Ancestral Health Symposium, was kind enough to send me this paper - "Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1.". The paper is a bit technical. But hearkens back to a previous blog entry, Brain Efficiency. In that entry I talked about how Parkinson's Disease comes about when the dopamine-making neurons of the substantia nigra (thanks, Ned) poop out for some reason. No dopamine in the substantia nigra, and you get stiffness, dementia, tremor - Parkinson's Disease. Parkinson's is another one of those diseases that seems to be increasing faster than we might expect for the aging population. It is postulated that oxidative stress causes the problems (oxidative stress means burn-out, basically. Too much gas for too long, too much build-up of the toxic byproducts of making energy). The burn-out happens in the mitochondria, the energy factories of the cells (which makes sense). But no one knows why the mitochondria in the substantia nigra would be more vulnerable than the mitochondria in other cells.
Increasing the efficiency of the mitochondria by using certain supplements (such as coenzyme Q and creatine) which are also available from meat and organs from animal foods is currently being investigated as treatment for Parkinson's Disease. This new paper has some evidence for a mechanism why the mitochondria in the substantia nigra are so vulnerable as to be the canaries in the coal mine.
In the paper, researchers investigated some mouse substantia nigra(s?) and found that those particular neurons have some interesting properties. They seem to pulse in energy output, rather like a pacemaker of some sort. The pacemaking requires a lot of energy, as the cells have to let go of their energy and then build it up again at regular intervals. Since they burn through more energy doing this pacemaking than other dopamine-making neurons in neighboring brain areas, they seem to be more vulnerable to excess oxidative stress. So more vulnerable to burn-out resulting in Parkinson's Disease.
The solution (or, perhaps better stated as the possible prevention) is, of course, always pretty much the same. Eat a diet of nutrient-rich foods and avoid poisons that will stress your brain. Say no to excess fructose, wheat, and omega 6 fatty-acids and fake, processed foods. I have to say that going out into the real world on this vacation (not my kitchen or pantry) shows me once more just how ubiquitous the poisons are. We checked out some "pizza topping" cheese-like substance in a bag right next to the real cheese which looked like mozzarella, but was actually soybean oil, corn starch, and potato starch. Ick! And guess what - that mayonnaise "with olive oil" is still mostly soybean oil. Avoid!
CoEnzyme Q rides around the body in your cholesterol carriers, so sufficient cholesterol is important. We can make creatine, but when we eat it we get it mostly from muscle flesh. Vegetarians are low in creatine.
We have a certain design spec. It is remarkably flexible, yet in the post-industrial age we have managed to scribble far, far outside the lines of what our bodies consider food. Once again, straying too far for too many meals is really not a good idea.
But anyway. A few weeks ago, Dr. Aaron Blaisdell, who I'm told will have access to all the best parties at the Ancestral Health Symposium, was kind enough to send me this paper - "Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1.". The paper is a bit technical. But hearkens back to a previous blog entry, Brain Efficiency. In that entry I talked about how Parkinson's Disease comes about when the dopamine-making neurons of the substantia nigra (thanks, Ned) poop out for some reason. No dopamine in the substantia nigra, and you get stiffness, dementia, tremor - Parkinson's Disease. Parkinson's is another one of those diseases that seems to be increasing faster than we might expect for the aging population. It is postulated that oxidative stress causes the problems (oxidative stress means burn-out, basically. Too much gas for too long, too much build-up of the toxic byproducts of making energy). The burn-out happens in the mitochondria, the energy factories of the cells (which makes sense). But no one knows why the mitochondria in the substantia nigra would be more vulnerable than the mitochondria in other cells.
Increasing the efficiency of the mitochondria by using certain supplements (such as coenzyme Q and creatine) which are also available from meat and organs from animal foods is currently being investigated as treatment for Parkinson's Disease. This new paper has some evidence for a mechanism why the mitochondria in the substantia nigra are so vulnerable as to be the canaries in the coal mine.
In the paper, researchers investigated some mouse substantia nigra(s?) and found that those particular neurons have some interesting properties. They seem to pulse in energy output, rather like a pacemaker of some sort. The pacemaking requires a lot of energy, as the cells have to let go of their energy and then build it up again at regular intervals. Since they burn through more energy doing this pacemaking than other dopamine-making neurons in neighboring brain areas, they seem to be more vulnerable to excess oxidative stress. So more vulnerable to burn-out resulting in Parkinson's Disease.
The solution (or, perhaps better stated as the possible prevention) is, of course, always pretty much the same. Eat a diet of nutrient-rich foods and avoid poisons that will stress your brain. Say no to excess fructose, wheat, and omega 6 fatty-acids and fake, processed foods. I have to say that going out into the real world on this vacation (not my kitchen or pantry) shows me once more just how ubiquitous the poisons are. We checked out some "pizza topping" cheese-like substance in a bag right next to the real cheese which looked like mozzarella, but was actually soybean oil, corn starch, and potato starch. Ick! And guess what - that mayonnaise "with olive oil" is still mostly soybean oil. Avoid!
CoEnzyme Q rides around the body in your cholesterol carriers, so sufficient cholesterol is important. We can make creatine, but when we eat it we get it mostly from muscle flesh. Vegetarians are low in creatine.
We have a certain design spec. It is remarkably flexible, yet in the post-industrial age we have managed to scribble far, far outside the lines of what our bodies consider food. Once again, straying too far for too many meals is really not a good idea.
Friday, December 24, 2010
Secrets of the Synapse
Merry Christmas Eve, y'all! I'm in Texas and therefore blogging in a Texas accent currently. Also, I ate some Tex-Mex, which aside from the vegetable oils and corn and cheese and beans is totally paleo. It is too much to hope that the restaurant we went to used the traditional lard.
But life goes on, the year comes to a close, and earlier this month a lovely "Brief Communication" was published in Nature Neuroscience. Now Nature Neuroscience is some hard core brain journaling. I like to think I know more about the brain than the average soul, but when I read the titles of the articles in Nature Neuroscience, I understand the gist of about half of them.
This paper, "Characterization of the proteome, diseases, and evolution of the human synaptic density" is well worth a squint or two. Here's a full text link. What it comes down to is that the researchers were able to find the actual proteins and their associated genes linked to all sorts of neurological disease via human brain sampling and a rather amazing use of free online databases. It's the wikipedia of neuroscience, without the amateur editing, described in a stunning three pages.
Basically, the researchers took brain neocortex samples from 9 adults and used some advanced chemical sorting techniques to to identify all the proteins in the sample, which was calibrated to be a sample of the nerve synapse (specifically the post-synaptic area). Just as when we call all DNA the "genome," when we identify all the proteins, we have what is called a "proteome."
The 748 proteins found in all three replications of the experiment were recorded into a freely available online database. Then the data were compared to the Online Mendelian Inheritance in Man database, which has information about genetic diseases from linkage studies. Linkage studies are usually done comparing siblings and parents with genetic diseases. If there is enough available data, linkage studies will give you sections of chromosomes, and in some cases, even specific genes associated with the diseases (here's a nice mini-primer on the difference between linkage and association genetic studies - my previous post on migraines reviewed an association genetic study).
In short, our researchers compared the data and found 269 diseases resulting from mutations in 199 genes. 133 of these diseases specifically affect the nervous system (80% central, 20% peripheral). Alzheimer's, Parkinson's, Huntington's diseases and disorders resulting in mental retardation, movement disorders and ataxia, epilepsy, and many rare diseases were all scooped up in this analysis.
Breaking down the data further, the scientists found 21 neural phenotypes (a phenotype is a gene expression - we each have genes for blue eyes or brown eyes or both or neither, but our phenotype is our eye color). A phenotype for mental retardation represented 40 genes, while 20 genes represented spasticity. The large number of genes In these sets are thought to mean that the post-synaptic area of the human brain is exceptionally important in these disorders.
The researchers didn't stop there (we're still on the first page of the paper!) The next step was to compare the human data to the much more specific set of mouse data (more specific because we do all sorts of enlightening but gruesome experiments on mice that we are not able to do on humans) From that they were able to find specific sets of genes related to actual cellular morphology linked to certain, especially important "enriched" phenotypes. The enriched phenotypes, associated with lots of neuronal functioning and disease, include components of known very important signaling mechanisms (the NMDA receptor and associated proteins, for example).
Next the human neural coding sequences were compared with various primates and mice using the dN/dS ratio. This data analysis compares the differences in specific samples (the post-synaptic neuron genes from human and chimpanzees, for example) to the expected (average) rate of genetic change over time. Humans and mice diverged 90 million years ago, yet the post-synaptic neuronal genetic dN/dS ratio was "very significantly" less than the variation between the entire human and mouse genome (we're talking a p value of 10 to the -148). Human neuronal genes were, not surprisingly, also very significantly similar to the primate genes studied compared to the whole human and various primate genomes (with similarly minuscule and thus highly significant p values). Mice and rats diverged 20 million years ago from each other, and their post-synaptic genes are also much more similar than you would expect to each other. All this means that the forces of evolution have conserved these important genes over millions of years, meaning they had better work just so, or your offspring won't survive.
The scientists also compared the conservation of these post-synaptic genes to the genes of other areas of the brain (which are also highly conserved), and found the post-synaptic genes were more conserved than the other brain sets, and also more conserved than other genes for basic cellular components (such as the endoplasmic reticulum, the mitochondria, and the nucleus). Highly interconnected "hub" proteins were also more conserved than other post-synaptic genes, showing that the structure of the synapse seems to mediate the evolutionary conservation of the gene sequences involved.
I'll say. It might also show us that animal studies involving the synapse might give us fairly accurate information related to humans, especially compared to information obtained from dietary studies or the like. The information from this study is a holiday present to neuroscientists everywhere. And shows us the vast potential of comparing existing databases to new data to create working protein maps of what is actually going on in the synapse or other biologic systems.
Amazing. Nearly miraculous. One way or another, the secrets of our complex brains will eventually be revealed.
- Posted using BlogPress from my iPhone
But life goes on, the year comes to a close, and earlier this month a lovely "Brief Communication" was published in Nature Neuroscience. Now Nature Neuroscience is some hard core brain journaling. I like to think I know more about the brain than the average soul, but when I read the titles of the articles in Nature Neuroscience, I understand the gist of about half of them.
This paper, "Characterization of the proteome, diseases, and evolution of the human synaptic density" is well worth a squint or two. Here's a full text link. What it comes down to is that the researchers were able to find the actual proteins and their associated genes linked to all sorts of neurological disease via human brain sampling and a rather amazing use of free online databases. It's the wikipedia of neuroscience, without the amateur editing, described in a stunning three pages.
Basically, the researchers took brain neocortex samples from 9 adults and used some advanced chemical sorting techniques to to identify all the proteins in the sample, which was calibrated to be a sample of the nerve synapse (specifically the post-synaptic area). Just as when we call all DNA the "genome," when we identify all the proteins, we have what is called a "proteome."
The 748 proteins found in all three replications of the experiment were recorded into a freely available online database. Then the data were compared to the Online Mendelian Inheritance in Man database, which has information about genetic diseases from linkage studies. Linkage studies are usually done comparing siblings and parents with genetic diseases. If there is enough available data, linkage studies will give you sections of chromosomes, and in some cases, even specific genes associated with the diseases (here's a nice mini-primer on the difference between linkage and association genetic studies - my previous post on migraines reviewed an association genetic study).
In short, our researchers compared the data and found 269 diseases resulting from mutations in 199 genes. 133 of these diseases specifically affect the nervous system (80% central, 20% peripheral). Alzheimer's, Parkinson's, Huntington's diseases and disorders resulting in mental retardation, movement disorders and ataxia, epilepsy, and many rare diseases were all scooped up in this analysis.
Breaking down the data further, the scientists found 21 neural phenotypes (a phenotype is a gene expression - we each have genes for blue eyes or brown eyes or both or neither, but our phenotype is our eye color). A phenotype for mental retardation represented 40 genes, while 20 genes represented spasticity. The large number of genes In these sets are thought to mean that the post-synaptic area of the human brain is exceptionally important in these disorders.
The researchers didn't stop there (we're still on the first page of the paper!) The next step was to compare the human data to the much more specific set of mouse data (more specific because we do all sorts of enlightening but gruesome experiments on mice that we are not able to do on humans) From that they were able to find specific sets of genes related to actual cellular morphology linked to certain, especially important "enriched" phenotypes. The enriched phenotypes, associated with lots of neuronal functioning and disease, include components of known very important signaling mechanisms (the NMDA receptor and associated proteins, for example).
Next the human neural coding sequences were compared with various primates and mice using the dN/dS ratio. This data analysis compares the differences in specific samples (the post-synaptic neuron genes from human and chimpanzees, for example) to the expected (average) rate of genetic change over time. Humans and mice diverged 90 million years ago, yet the post-synaptic neuronal genetic dN/dS ratio was "very significantly" less than the variation between the entire human and mouse genome (we're talking a p value of 10 to the -148). Human neuronal genes were, not surprisingly, also very significantly similar to the primate genes studied compared to the whole human and various primate genomes (with similarly minuscule and thus highly significant p values). Mice and rats diverged 20 million years ago from each other, and their post-synaptic genes are also much more similar than you would expect to each other. All this means that the forces of evolution have conserved these important genes over millions of years, meaning they had better work just so, or your offspring won't survive.
The scientists also compared the conservation of these post-synaptic genes to the genes of other areas of the brain (which are also highly conserved), and found the post-synaptic genes were more conserved than the other brain sets, and also more conserved than other genes for basic cellular components (such as the endoplasmic reticulum, the mitochondria, and the nucleus). Highly interconnected "hub" proteins were also more conserved than other post-synaptic genes, showing that the structure of the synapse seems to mediate the evolutionary conservation of the gene sequences involved.
The human [post-synaptic density sampled for this experiment] has a high degree of molecular complexity, with over 1000 proteins,..combinations of proteins regulate the phenotypes of over 130 brain diseases. It is possible, indeed likely, that the proteins identified represent an overall synaptic parts list, with subsets of synapses containing subsets of these proteins... Our data provide a valuable resource and template for investigating human synapse function and suggest new diagnostic and therapeutic approaches.
I'll say. It might also show us that animal studies involving the synapse might give us fairly accurate information related to humans, especially compared to information obtained from dietary studies or the like. The information from this study is a holiday present to neuroscientists everywhere. And shows us the vast potential of comparing existing databases to new data to create working protein maps of what is actually going on in the synapse or other biologic systems.
Amazing. Nearly miraculous. One way or another, the secrets of our complex brains will eventually be revealed.
- Posted using BlogPress from my iPhone