According to this review, a simple dietary change towards lower carbohydrate intake and higher fats intake, may be efficiently protective against AD. >> read the article
Neurobiology of autism-related conditions
Related: Mirror neurons, autism, and the theory of mind
Because of its relative inaccessibility, scientists have only recently been able to study the brain systematically. But with the emergence of new brain imaging tools—computerized tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI), study of the structure and the functioning of the brain can be done. With the aid of modern technology and the new availability of both normal and autism tissue samples to do postmortem studies, researchers will be able to learn much through comparative studies.
Postmortem and MRI studies have shown that many major brain structures are implicated in autism. This includes the cerebellum, cerebral cortex, limbic system, corpus callosum, basal ganglia, and brain stem (1). Other research is focusing on the role of neurotransmitters such as serotonin, dopamine, and epinephrine.
Research into the causes of autism spectrum disorders is being fueled by other recent developments. Evidence points to genetic factors playing a prominent role in the causes for ASD. Twin and family studies have suggested an underlying genetic vulnerability to ASD (2). To further research in this field, the Autism Genetic Resource Exchange, a project initiated by the Cure Autism Now Foundation, and aided by an NIMH grant, is recruiting genetic samples from several hundred families. Each family with more than one member diagnosed with ASD is given a 2-hour, in-home screening. With a large number of DNA samples, it is hoped that the most important genes will be found. This will enable scientists to learn what the culprit genes do and how they can go wrong.
Another exciting development is the Autism Tissue Program (http://www.brainbank.org), supported by the Autism Society of America Foundation, the Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute at the University of California, Davis, and the National Alliance for Autism Research. The program is aided by a grant to the Harvard Brain and Tissue Resource Center (http://www.brainbank.mclean.org), funded by the National Institute of Mental Health (NIMH) and the National Institute of Neurological Disorders and Stroke (NINDS). Studies of the postmortem brain with imaging methods will help us learn why some brains are large, how the limbic system develops, and how the brain changes as it ages. Tissue samples can be stained and will show which neurotransmitters are being made in the cells and how they are transported and released to other cells. By focusing on specific brain regions and neurotransmitters, it will become easier to identify susceptibility genes.
Recent neuroimaging studies have shown that a contributing cause for autism may be abnormal brain development beginning in the infant’s first months. This“growth dysregulation hypothesi” holds that the anatomical abnormalities seen in autism are caused by genetic defects in brain growth factors. It is possible that sudden, rapid head growth in an infant may be an early warning signal that will lead to early diagnosis and effective biological intervention or possible prevention of autism (3).
References
- Akshoomoff N, Pierce K, Courchesne E. The neurobiological basis of autism from a developmental perspective. Development and Psychopathology, 2002; 14: 613-634.
- Korvatska E, Van de Water J, Anders TF, Gershwin ME. Genetic and immunologic considerations in autism. Neurobiology of Disease, 2002; 9: 107-125.
- Courchesne E. Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA, 2003; 290(3): 337-344.
Reprinted from NIHM
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Growth hormone and its releasers: a hope for Alzheimer’s?
The growth hormone (GH) secretion declines as we age (by 14% per decade), the process called somatopause. Drugs like pyridostigmine (an acetylcholinesterase inhibitor) are able to enhance GH secretion, but its clinical use is limited due to the strong side effects. Rivastigmine, a drug for Alzheimer’s disease (AD), was found to enhance GH release (Gerontology. 2003;49:191–195).
Oral administration of certain amino acids (arginine, glutamine, glycine, and lysine) increased the release of endogenous GH (Nutrition. 2002;18:657–661); the doses of arginine were 0.5 or 1 g/kg body weight increased GH level (J Clin Endocrinol Metab, 2011 ; Vol. 43 (3): 582-586) or roughly 35 to 70 g a day.
Arginine dissolved in distilled water was infused over a thirty-minute period in doses 1/12, 1/6 and 1/4 g. per pound of body weight. Only the highest dose (average 37.5 g total) was found to be effective in this administration mode. Interestingly, the responses of GH among females remain significantly higher than those among males (N Engl J Med 1967; 276:434-439).
The mixture of L-arginine, L-glutamine, L-lysine, and glycine at a ratio of 37:30:18.5:14.5) added as 5% of the daily meals total has been found to increase the release of endogenous GH. When mice were fed a diet containing GH-releasing supplements they had significantly fewer memory impairments and changes in acetylcholine level in hippocampus induced by Alzheimer’s amyloid beta 1–42 (J Pharmacol Sci; 2005, 99, 117 – 120).
Recently, a clinical target for improving the conditions of AD may be the activation not of GH alone but the entire GH/insulin-like growth factor-I (IGF-I) brain axis. IGF-I alone is also considered a physiological regulator of brain amyloid levels with therapeutic potential (Nature Medicine, 2002; 8, 1390 – 1397)
The growth hormone (GH) secretion declines as we age (by 14% per decade), the process called somatopause. Drugs like pyridostigmine (an acetylcholinesterase inhibitor) are able to enhance GH secretion, but its clinical use is limited due to the strong side effects. Rivastigmine, a drug for Alzheimer’s disease (AD), was found to enhance GH release (Gerontology. 2003;49:191–195).
Oral administration of certain amino acids (arginine, glutamine, glycine, and lysine) increased the release of endogenous GH (Nutrition. 2002;18:657–661); the doses of arginine were 0.5 or 1 g/kg body weight increased GH level (J Clin Endocrinol Metab, 2011 ; Vol. 43 (3): 582-586) or roughly 35 to 70 g a day.
Arginine dissolved in distilled water was infused over a thirty-minute period in doses 1/12, 1/6 and 1/4 g. per pound of body weight. Only the highest dose (average 37.5 g total) was found to be effective in this administration mode. Interestingly, the responses of GH among females remain significantly higher than those among males (N Engl J Med 1967; 276:434-439).
The mixture of L-arginine, L-glutamine, L-lysine, and glycine at a ratio of 37:30:18.5:14.5) added as 5% of the daily meals total has been found to increase the release of endogenous GH. When mice were fed a diet containing GH-releasing supplements they had significantly fewer memory impairments and changes in acetylcholine level in hippocampus induced by Alzheimer’s amyloid beta 1–42 (J Pharmacol Sci; 2005, 99, 117 – 120).
Recently, a clinical target for improving the conditions of AD may be the activation not of GH alone but the entire GH/insulin-like growth factor-I (IGF-I) brain axis. IGF-I alone is also considered a physiological regulator of brain amyloid levels with therapeutic potential (Nature Medicine, 2002; 8, 1390 – 1397)
Vitamins C and E to prevent Alzheimer’s
In 1980s, 65% of all East Boston residents over the age of 65 were recruited in the study of neuroprotective effects of vitamins C and E. None of the people taking vitamin C or vitamin E developed Alzheimer’s disease when followed up in 4.5 years while among vitamin C non-users, 85% developed the disease. Among vitamin E non-users, 14% developed Alzheimer’s (1)
I was shown that supplementation with vitamin E and/or vitamin C might be useful in maintaining brain acetylcholinesterase (footnote a) activity at the normal level and serotonin (footnote b) concentration for some extent under the condition to induce experimental dementia in experimental animals (2)
High intake of vitamin E from food (tocopherol), but not from supplements (which usually contain alpha-tocopherol), is shown to reduce incidence of Alzheimer’s disease. The most common alpha-tocopherol alone may not be sufficient in the protective effects (3)
Sources
MC Morris et al, Vitamin E and Vitamin C Supplement Use and Risk of Incident Alzheimer Disease. Alzheimer Disease & Associated Disorders, 1998 – V12 – 3
LEE Lilha et al., Effect of supplementation of vitamin E and vitamin C on brain acetylcholinesterase activity and neurotransmitter levels in rats treated with scopolamine, an inducer of dementia, Journal of nutritional science and vitaminology, 2001, vol. 47, no5, pp. 323-328
MC Morris et. al., Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutrition, Vol. 81, No. 2, 508-514, February 2005
Footnotes
a) Acetylcholinesterase (AChE) is an enzyme that degrades the neurotransmitter acetylcholine at neuromuscular junctions and cholinergic synaptic transmission in the brain.
b) Serotonin is a neurotransmitter found in the central nervous system. It is best known as a “happiness hormone” though it’s no hormone but monoamine.
In 1980s, 65% of all East Boston residents over the age of 65 were recruited in the study of neuroprotective effects of vitamins C and E. None of the people taking vitamin C or vitamin E developed Alzheimer’s disease when followed up in 4.5 years while among vitamin C non-users, 85% developed the disease. Among vitamin E non-users, 14% developed Alzheimer’s (1)
I was shown that supplementation with vitamin E and/or vitamin C might be useful in maintaining brain acetylcholinesterase (footnote a) activity at the normal level and serotonin (footnote b) concentration for some extent under the condition to induce experimental dementia in experimental animals (2)
High intake of vitamin E from food (tocopherol), but not from supplements (which usually contain alpha-tocopherol), is shown to reduce incidence of Alzheimer’s disease. The most common alpha-tocopherol alone may not be sufficient in the protective effects (3)
Sources
- MC Morris et al, Vitamin E and Vitamin C Supplement Use and Risk of Incident Alzheimer Disease. Alzheimer Disease & Associated Disorders, 1998 – V12 – 3
- LEE Lilha et al., Effect of supplementation of vitamin E and vitamin C on brain acetylcholinesterase activity and neurotransmitter levels in rats treated with scopolamine, an inducer of dementia, Journal of nutritional science and vitaminology, 2001, vol. 47, no5, pp. 323-328
- MC Morris et. al., Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutrition, Vol. 81, No. 2, 508-514, February 2005
Footnotes
a) Acetylcholinesterase (AChE) is an enzyme that degrades the neurotransmitter acetylcholine at neuromuscular junctions and cholinergic synaptic transmission in the brain.
b) Serotonin is a neurotransmitter found in the central nervous system. It is best known as a “happiness hormone” though it’s no hormone but monoamine.
Why music is good for the brain
The study conducted by researchers at McGill University in Montreal and published in January issue of Nature Neuroscience showed that the music increased dopamine levels in certain areas of the brain. Various types of music were shown to be effective depending on individual preferences. >> More at Brainfuels.com
Should we start exercising early in life to postpone or prevent age-related cognitive decline?
Exercise during midlife comparing with exercise during late life
Most of the studies into the protective effects of exercise against cognitive decline, dementia, and Alzheimer’s disease, followed the elderly people starting their 65s and watched the results, which were relevant to the beneficial effects in late life. However, there are some results where a large cohort of 65-79-year olds has been followed-up for around 21 years so information about physical activity during midlife was available. Those who who participated in at least “leisure-time physical activity” during midlife had significantly lower risks of dementia or Alzheimer’s disease comparing with those who did not exercise at all [1].
Another study has suggested that physical activity at even earlier ages (physical activity between ages 15 and 25 years was asked retrospectively) can improve or preserve cognitive ability in late life [2]. This cognitive decline risk reduction is at least comparable to the eisks reduction reported in studies of physical activity in older persons. Thus, midlife physical activity might be as important for preventing later cognitive decline as is physical activity at older ages.
Sources
- Rovio S, et al. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol 2005;4:705–11
- Dik M, Deeg DJ, Visser M, Jonker C. Early life physical activity and cognition at old age. J Clin Exp Neuropsychol 2003;25:643–53
Resveratrol and curcumin, plant’s own weapons that protect the brain
According to Michael Wong, MD, PhD (1), although there’s a noticeable progress in anti-epileptic drug development, two obstacles remain unchanged for many decades:
1. The number of cases resistant to the best and newest drugs does not decrease
2. The best drugs address symptoms and not the cause of the disease, namely, they might suppress the seizures but they cannot make them disappear. As a result of such a failure, we still have no anti-epileptic therapies.
Recent studies, however, addresses potential neuroprotective and anti-epileptogenic actions of substances naturally occurring in plants. For example, Resveratrol (a phytoalexin) is found in plants such as peanuts and grapes, but it’s especially abundant in red wine. In plants, Resveratrol defends the cells against the consequences of injury, parasitics, and infectious diseases — hence its antiinflammatory, antioxidant, anti-tumor, and, if given to animals, its neuroprotective effects.
In the article “Protective Effect of Resveratrol Against Kainate-Induced Temporal Lobe Epilepsy in Rats” Resveratrol is described as a potent anti-epilepsy agent, which protects against epileptogenesis (not just against seizures) in animal model of temporal lobe epilepsy (2).
Another success story was told about curcumin, which is the major ingredient in the popular Indian spice, tumeric. Tumeric has been used for centuries in parts of India as an herbal therapy; including treatment of Alzheimer’s disease and epilepsy. As resveratrol, curcumin has been shown to inhibit acute seizures. The recent study (3) studied the effect of curcumin on epileptogenesis in a rat model of post-traumatic epilepsy. Curcumin decreased the development of and seizures and improved memory and learning.
1. M Wong. HERBS AND SPICES: UNEXPECTED SOURCES OF ANTIEPILEPTOGENIC DRUG TREATMENTS? Epilepsy Currents, Vol. 10, No. 1 2010 pp. 21–23
2. Protective Effect of Resveratrol Against Kainate-Induced Temporal Lobe Epilepsy in Rats. Wu Z, Xu Q, Zhang
L, Kong D, Ma R, Wang L. Neurochem Res 2009;34(8):1393–1400.
3. Curcumin Protects Against Electrobehavioral Progression of Seizures in the Iron-Induced Experimental Model
of Epileptogenesis. Jyoti A, Sethi P, Sharma D. Epilepsy Behav 2009;14(2):300–308.
Related: The eight mechanisms of anti-Alzheimer’s effects of curcumin
HERBS AND SPICES: UNEXPECTED SOURCES OF ANTIEPILEPTOGENIC DRUG TREATMENTS?
According to Michael Wong, MD, PhD (1), although there’s a noticeable progress in anti-epileptic drug development, two obstacles remain unchanged for many decades.
- The number of cases resistant to the best and newest drugs does not decrease
- The best drugs address symptoms and not the cause of the disease, namely, they might suppress the seizures but they cannot make them disappear. As a result of such a failure, we still have no anti-epileptic therapies.
Recent studies, however, address potential neuroprotective and anti-epileptogenic actions of substances naturally occurring in plants. For example, Resveratrol (a phytoalexin) is found in plants such as peanuts and grapes, but it’s especially abundant in red wine. In plants, Resveratrol defends the cells against the consequences of injury, parasitics, and infectious diseases — hence its antiinflammatory, antioxidant, anti-tumor, and, if given to animals, its neuroprotective effects.
In the article “Protective Effect of Resveratrol Against Kainate-Induced Temporal Lobe Epilepsy in Rats” Resveratrol is described as a potent anti-epilepsy agent, which protects against epileptogenesis (not just against seizures) in animal model of temporal lobe epilepsy (2).
Another success story was told about curcumin, which is the major ingredient in the popular Indian spice, tumeric. Tumeric has been used for centuries in parts of India as an herbal therapy; including treatment of Alzheimer’s disease and epilepsy. As resveratrol, curcumin has been shown to inhibit acute seizures. The recent study (3) studied the effect of curcumin on epileptogenesis in a rat model of post-traumatic epilepsy. Curcumin decreased the development of and seizures and improved memory and learning.
Sources
- M Wong. CURRENT LITERATURE IN BASIC SCIENCE. Epilepsy Currents, Vol. 10, No. 1 2010 pp. 21–23
- Protective Effect of Resveratrol Against Kainate-Induced Temporal Lobe Epilepsy in Rats. Wu Z, Xu Q, Zhang
- L, Kong D, Ma R, Wang L. Neurochem Res 2009;34(8):1393–1400.
- Curcumin Protects Against Electrobehavioral Progression of Seizures in the Iron-Induced Experimental Model of Epileptogenesis. Jyoti A, Sethi P, Sharma D. Epilepsy Behav 2009;14(2):300–308.
Alzheimer’s Facts
Alzheimer’s Disease Statistics
• Alzheimer’s affects approximately 4.5 million Americans and is
expected to affect up to 16 million by 2050.
• Alzheimer’s affects approximately 5 percent of men and women
ages 65–74.
• Nearly half of people 85 and older have Alzheimer’s.
• Alzheimer’s must be distinguished from mild cognitive impairment
and normal age-related memory changes.
(National Institute of Aging. Alzheimer’s Disease Information, May 9, 2006)
Physical and mental health: same strategies
Research evidence is accumulating, showing that many of the same strategies for maintaining physical health are also applicable for maintaining brain plasticity and good cognitive functioning throughout the lifespan. These studies reinforce the message that exercise—physical and mental—is an essential part of any comprehensive health program (ALTERNATIVE & COMPLEMENTARY THERAPIES—OCTOBER 2006 pp 222-227)
Exercise and balance for intelligence
Exercise can help maintain balance, and balance in the elderly has been highly correlated with performance measures of mental abilities such as general intelligence, memory, and reaction time. Balance thus serves as a biomarker of cerebroarterial blood flow
and age-related global neurophysiologic status (Neuropsychologia 2006;44:1978–1983).
Meditation and cortex thickness
Magnetic resonance imaging to assess cortical thickness revealed that brain areas—such as the prefrontal cortex involved with memory, attention, and sensory processing—were approximately 5 percent thicker in the subjects who meditated compared with those who did not. This difference was most pronounced in older participants, suggesting that meditation might offset agerelated cortical thinning (Neuroreport 2005;16:1893–1897)
Vitamins C and E, separately or combined
Combined deficiency in vitamins C and E is a risk factor for neuronal death and brain necrosis
Vitamin C easily crosses the blood brain barrier and its transport into the brain is mediated by glucose transporters. Vitamin C concentrations in the brain exceed those in blood by 10-fold. In humans, hypovitaminosis C correlated with brain damage in patients with head trauma (Stroke. 2001;32:898-902). The vitamin C has important functions in the brain, for example, protecting neuronal membranes from oxidative damage acting as a scavenger of free radicals.
Another free radical scavenger Vitamin E (-tocopherol) inhibits the amyloid peptide characteristic for Alzheimer’s disease known to induced cell death (Biochemical and Biophysical Research Communications Volume 186, Issue 2, 31 July 1992, Pages 944-950).
The results of a study of Guinea Pigs’s fed either on normal or vitamin-deficient diets showed that while moderate deficiencies of vitamins E or C didn’t result in serious brain changes, their combined moderate deficienciescaused degenerative changes in the guinea pig brains in only 5 days after vitamins were removed from the feed.
Interestingly, the deficiencies in either E or C vitamins had only moderate consequences, but their combination caused severe brain lesions – inflammation, cell death with necrosis and apoptosis and animals’ death (Nutr. 136:1576-1581, June 2006).
Combined deficiency in vitamins C and E is a risk factor for neuronal death and brain necrosis.
Vitamin C easily crosses the blood brain barrier and its transport into the brain is mediated by glucose transporters. Vitamin C concentrations in the brain exceed those in blood by 10-fold. In humans, hypovitaminosis C correlated with brain damage in patients with head trauma (Stroke. 2001;32:898-902). The vitamin C has important functions in the brain, for example, protecting neuronal membranes from oxidative damage acting as a scavenger of free radicals.
Another free radical scavenger Vitamin E (-tocopherol) inhibits the amyloid peptide characteristic for Alzheimer’s disease known to induced cell death (Biochemical and Biophysical Research Communications Volume 186, Issue 2, 31 July 1992, Pages 944-950).
The results of a study of Guinea Pigs’s fed either on normal or vitamin-deficient diets showed that while moderate deficiencies of vitamins E or C didn’t result in serious brain changes, their combined moderate deficienciescaused degenerative changes in the guinea pig brains in only 5 days after vitamins were removed from the feed.
Interestingly, the deficiencies in either E or C vitamins had only moderate consequences, but their combination caused severe brain lesions – inflammation, cell death with necrosis and apoptosis and animals’ death (Nutr. 136:1576-1581, June 2006).
