[quote]
NewKerala.com: News Source
US News
Morphine affects brain's synapse process
PROVIDENCE, R.I., April 26: A U.S. study has found morphine blocks the brain's ability to strengthen inhibitory synapse connections -- an important finding for addiction therapy.
Brown University Professor Julie Kauer and colleagues found as little as a single dose of morphine could contribute to addiction. The study also supports a theory that addiction is a disease of learning and memory.
In the study, the researchers found long-term potentiation, or LTP, is blocked in the brains of rats given as little as a single dose of morphine. The drug's impact was powerful, with LTP continuing to be blocked 24 hours later -- long after the drug was out of the animal's system.
"The persistence of the effect was stunning," Kauer said. "This is your brain on drugs."
Kauer and her team not only recorded cellular changes caused by morphine but also molecular ones. In fact, the researchers pinpointed the very molecule that morphine disables -- guanylate cyclase. That enzyme, or inhibitory neurons themselves, would be effective targets for drugs that prevent or treat addiction.
The study by Kauer, Fereshteh Nugent and Esther Penick, appears in the journal Nature.
--- UPI
[/quote]
Hm.
If the indeed this damage done to synapses by opiates is sustained and there is indeed long term damage inflicted to the dopaminergic system...I was wondering if perhaps a therapeutic solution...
From a pharmacological perspective, Hydergine (ergoloid mesylates), ALCAR (acteyl-l-carnitine), Ashwagandha (Withania somnifera), and Centella asiatica (Gotu Kola) [and perhaps some more that I left out here], might prove effective for individuals recovering from brain damage from an opiate addiction (be it morphine, heroin, methadone, etc.) restore whatever cognitive function may have been compromised by damage to synapses -- especially in the dopaminergic system.
These are just a hypotheses for now...
The evidence to support the Hydergine (ergoloid mesylates) and ALCAR hypotheses comes from humans and mice; whereas the evidence for the remaining herbs is mostly from in vitro and rat studies. Also some of the naturalistic use of the aforementioned herbs seems to be somewhat inconclusive and circumstantial, but hereya go anyways....
Hydergine seems to have effects on these parts of the brain; first the rat data; Hydergine increasing the number of synapses (dendrite growth) -- here we assume an aged rat would benefit similarly to a damaged rat:
[quote]
J Gerontol. 1987 Sep;42(5):482-6.
The effect of chronic hydergine treatment on the plasticity of synaptic junctions in the dentate gyrus of aged rats.
Bertoni-Freddari C, Giuli C, Pieri C, Paci D, Amadio L, Ermini M, Dravid A.
The number of synapses (Nv) , the surface density of contact zones (Sv) as well as the average size (S) of E-PTA stained synapses in the supragranular layer of the dentate gyrus from adult (12 months), old (30 month), and Hydergine-treated old (30 months) rats were measured by using quantitative morphometric techniques. In old animals, Nv and Sv were significantly reduced, whereas S was significantly increased as compared with the values in adult rats. Hydergine (Codergocrine mesylate) treatment of old animals (3 mg/Kg/day for 4 weeks) influenced these three parameters, differentially. The Sv in aged animals receiving Hydergine, relative to that in untreated old rats, was significantly increased; the number and size of synapses in the treated old rats were significantly higher and smaller, respectively, than that in old controls. We interpret the present findings to indicate a modulating effect of Hydergine on the morphological plasticity of synaptic junctions in the dentate gyrus of aged rats.
[/quote]
[quote]
Pharmacol. 1985;16 Suppl 3:33-8.
A modulating effect of Hygergine on the synaptic plasticity of old rats.
[Article in English, French]
Bertoni-Freddari C, Giuli C, Pieri C, Paci D, Dravid A.
The morphological plasticity of E-PTA stained synaptic junctions was investigated by means of quantitative morphometry in the dentate gyrus supra-granular layer of adult, old and old-Hydergine treated rats. Numerical (Nv) and surface (Sv) density as well as average size of the synapses (S) were the three parameters considered. During aging, Nv and Sv significantly decrease whereas S increases. Hydergine treatment to old rats resulted in a significant increase of Nv and Sv and a significant decrease of S. Present findings are interpreted as a modulating effect of Hydergine on the synaptic plasticity of old rats.
PMID: 4094445 [PubMed - indexed for MEDLINE]
[/quote]
[quote]
Arch Gerontol Geriatr. 1990 May-Jun;10(3):287-96.
Effect of long term hydergine treatment on the age-dependent loss of mossy fibers and of granule cells in the rat hippocampus.
Amenta F, Jaton AL, Ricci A.
Dipartimento di Sanita Pubblica e Biologia Cellulare, Universita 'Tor Vergata', Rome, Italy; Dipartimento di Scienze Neurologiche, Universita 'La Sapienza', Rome, Italy.
The effects of senescence and of long-term Hydergine treatment on the density and pattern of mossy fibers and on the number of granule cells of the dentate gyrus were studied in the rat hippocampus. Timm's technique for the histochemical demonstration of tissue stores of zinc, associated with quantitative image analysis and microdensitometry, was used for the study of mossy fibers. Consistent with our previous studies, we observed an age-related reduction both in the area occupied by mossy fibers and in the intensity of Timm staining in the mossy fiber area. Moreover, the density of granule cells in the dentate gyrus of hippocampus was reduced with age. Hydergine administration (1 and 3 mg/kg/day, p.o.), started when the rats were 17 months old and continued for 4 months, significantly increased the area occupied by mossy fibers and the intensity of Timm staining in the hippocampus of senescent animals. Moreover, Hydergine treatment was found to counteract the age-dependent decrease in granule cell number in the dentate gyrus of the hippocampus. These findings suggest that treatment with Hydergine is effective in counteracting or in slowing down the morphological disorganization observable in the hippocampal formation with advancing age. Moreover, it is possible that the effects of Hydergine administration in elderly patients might be related to an effect at the level of the hippocampus.
PMID: 15374504 [PubMed - in process]
[/quote]
So essentially, this suggests that Hydergine makes the brain of aged rats "denser" -- a denser brain = more connections = probably more dentrites, &c.
This is a study that might suggest recovering opiate addicts could benefit from long term Hydergine treatment (assuming their dopaminergic system is damaged and this causes mental deterioration); however, these results are from elderly subjects and not recovering addicts. So it's just a hypothesis for now.
[quote]
Curr Med Res Opin. 1989;11(6):380-9.
Ergoloid mesylates ('Hydergine') in the treatment of mental deterioration in the elderly: a 6-month double-blind, placebo-controlled trial.
Rouy JM, Douillon AM, Compan B, Wolmark Y.
Centre de Soins, C.H.U.R., Nime, France.
A double-blind, placebo-controlled trial was carried out in 97 elderly patients with age-related mental deterioration to assess the efficacy of ergoloid mesylates in improving their symptoms. Patients were allocated at random to receive either 4.5 mg ergoloid mesylates per day or a matching placebo tablet and were followed-up for 6 months after the start of treatment. Clinical examinations were performed by the doctor, using the EACG rating scale (a French version of the Sandoz Clinical Assessment Geriatric scale), and by the nurse, using the NOSIE scale, when patients entered the trial and repeated after 2, 4 and 6 months. Changes in the factors (symptom groups) covered by these scales were subjected to statistical analysis. After 6-months' treatment, a statistically significant difference in favour of the ergoloid mesylates group was observed for cognitive deficits (p less than 0.05), anxiety and mood depression (p less than 0.01), unsociability (p less than 0.01), retardation (p less than 0.05) and irritability (p less than 0.001). Treatment was very well tolerated. It was also observed that there was a progressive increase in efficacy throughout the trial; this indicates that treatment with ergoloid mesylates in patients with mental deterioration should be long-term.
Publication Types:
* Clinical Trial
* Randomized Controlled Trial
PMID: 2651014 [PubMed - indexed for MEDLINE]
[/quote]
Why might an ex-drug addict consider taking high dose ALCAR? It seems to restore the functionality of aged (or in a drug addicts case "damaged") dopamine receptor systems -- which the opiate morphine appears to damage.
[quote]
Life Sci. 1994;54(17):1205-14.
Acetyl-L-carnitine affects aged brain receptorial system in rodents.
Castorina M, Ferraris L.
Institute for Research on Senescence, Sigma-Tau, Pomezia, Rome, Italy.
Acetyl-L-carnitine (ALCAR), the acetyl ester of carnitine, is regarded as a compound of considerable interest because of its capacity to counteract several physiological and pathological modifications typical of brain ageing processes. In particular, it has been demonstrated that ALCAR can counteract the age-dependent reduction of several receptors in the central nervous system of rodents, such as the NMDA receptorial system, the Nerve Growth Factor (NGF) receptors, those of glucocorticoids, neurotransmitters and others, thereby enhancing the efficiency of synaptic transmission, which is considerably slowed down by ageing. The present review thus postulates the importance of ALCAR administration in preserving and/or facilitating the functionality of carnitines, the concentrations of which are diminished in the brain of old animals.
Publication Types:
* Review
PMID: 8164502 [PubMed - indexed for MEDLINE]
[/quote]
[quote]
J Neurosci Res. 1991 Nov;30(3):555-9.
Effect of acetyl-L-carnitine on the dopaminergic system in aging brain.
Sershen H, Harsing LG Jr, Banay-Schwartz M, Hashim A, Ramacci MT, Lajtha A.
Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962.
We studied the effect of acetyl-L-carnitine (ALCAR) on dopamine release and the effect of long-term acetyl-L-carnitine treatment on age-related changes in striatal dopamine receptors and brain amino acid levels. In striatal tissue that had been incubated with [3H]dopamine, acetyl-L-carnitine increased the release of [3H]dopamine evoked by electrical stimulation. In striatal tissue from aged mice administered acetyl-L-carnitine for 3 months, the release of [3H]dopamine evoked by electrical stimulation was higher than that of its aged control; the release after a second stimulation was similar in the two groups. There was a significant decline in the number of D1 striatal dopamine receptors with age. The Bmax was 51% lower in 1.5-year-old mice than in 4-month-old animals. Administration of acetyl-L-carnitine for 3 months diminished the reduction in the binding of [3H]SCH-23390. [3H]Spiperone binding to D2 receptors was not decreased with age and was not affected by acetyl-L-carnitine treatment. Age-related decreases in levels of several amino acids were observed in several brain regions. Acetyl-L-carnitine lessened the reduction in the level of taurine only in the striatum. The findings confirm the multiple effects of acetyl-L-carnitine in brain, and suggest that its administration can have a positive effect on age-related changes in the dopaminergic system.
PMID: 1839317 [PubMed - indexed for MEDLINE]
[/quote]
Ashwagandha (Withania somnifera). Of the posted abstracts below that demonstrate neurite outgrowth activities -- ALL appear to be in vitro (or in culture -- not in a living organism -- so that's far from being able to claim these neuron regrowth effects will occur in a human) except for one -- this one -- in mice:
[quote]
Br J Pharmacol. 2005 Feb 14; [Epub ahead of print]
Neuritic regeneration and synaptic reconstruction induced by withanolide A.
Kuboyama T, Tohda C, Komatsu K.
[1] 1Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan [2] 221st Century COE Program, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan.
We investigated whether withanolide A (WL-A), isolated from the Indian herbal drug Ashwagandha (root of Withania somnifera), could regenerate neurites and reconstruct synapses in severely damaged neurons. We also investigated the effect of WL-A on memory-deficient mice showing neuronal atrophy and synaptic loss in the brain. Axons, dendrites, presynapses, and postsynapses were visualized by immunostaining for phosphorylated neurofilament-H (NF-H), microtubule-associated protein 2 (MAP2), synaptophysin, and postsynaptic density-95 (PSD-95), respectively. Treatment with Abeta(25-35) (10 muM) induced axonal and dendritic atrophy, and pre- and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL-A (1 muM) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons. WL-A (10 mumol kg(-1) day(-1), for 13 days, p.o.) recovered Abeta(25-35)-induced memory deficit in mice. At that time, the decline of axons, dendrites, and synapses in the cerebral cortex and hippocampus was almost recovered.WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks.
British Journal of Pharmacology advance online publication, 14 February 2005; doi:10.1038/sj.bjp.0706122.
PMID: 15711595 [PubMed - as supplied by publisher]
[/quote]
These are all in vitro:
[quote]
Axon- or dendrite-predominant outgrowth induced by constituents from Ashwagandha.
Kuboyama T, Tohda C, Zhao J, Nakamura N, Hattori M, Komatsu K.
Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
We previously reported that the methanol extract of Ashwagandha (roots of Dunal) induced dendrite extension in a human neuroblastoma cell line. In this study, we found that six of the 18 compounds isolated from the methanol extract enhanced neurite outgrowth in human neuroblastoma SH-SY5Y cells. Double immunostaining was performed in rat cortical neurons using antibodies to phosphorylated NF-H as an axonal marker, and to MAP2 as a dendritic marker. In withanolide A-treated cells, the length of NF-H-positive processes was significantly increased compared with vehicle-treated cells, whereas, the length of MAP2-positive processes was increased by withanosides IV and VI. These results suggest that axons are predominantly extended by withanolide A, and dendrites by withanosides IV and VI.
Copyright 2002 Lippincott Williams & Wilkins
[/quote]
[quote]
Neuroreport. 2000 Jun 26;11(9):1981-5.
Dendrite extension by methanol extract of Ashwagandha (roots of Withania somnifera) in SK-N-SH cells.
Tohda C, Kuboyama T, Komatsu K.
Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan.
Extension of dendrites and axons in neurons may compensate for and repair damaged neuronal circuits in the dementia brain. Our aim in the present study was to explore drugs activating neurite outgrowth and regenerating the neuronal network. We found that the methanol extract of Ashwagandha (roots of Withania somnifera; 5 microg/ml) significantly increased the percentage of cells with neurites in human neuroblastoma SK-N-SH cells. The effect of the extract was dose- and time-dependent mRNA levels of the dendritic markers MAP2 and PSD-95 by RT-PCR were found to be markedly increased by treatment with the extract, whereas those of the axonal marker Tau were not. Immunocytochemistry demonstrated the specific expression of MAP2 in neurites extended by the extract. These results suggest that the methanol extract of Ashwagandha promotes the formation of dendrites.
[/quote]
[quote]
Chem Pharm Bull (Tokyo). 2002 Jun;50(6):760-5.
Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities.
Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K.
Department of Metabolic Engineering, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Five new withanolide derivatives (1, 9-12) were isolated from the roots of Withania somnifera together with fourteen known compounds (2-8, 13-19). On the basis of spectroscopic and physiochemical evidence, compounds 1 and 9-12 were determined to be (20S,22R)-3 alpha,6 alpha-epoxy-4 beta,5 beta,27-trihydroxy-1-oxowitha-24-enolide (1), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside VIII, 9), 27-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside IX, 10), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranoside (withanoside X, 11), and (20R,22R)-1 alpha,3 beta,20,27-tetrahydroxywitha-5,24-dienolide 3-O-beta-D-glucopyranoside (withanoside XI, 12). Of the isolated compounds, 1, withanolide A (2), (20S,22R)-4 beta,5 beta,6 alpha,27-tetrahydroxy-1-oxowitha-2,24-dienolide (6), withanoside IV (14), withanoside VI (15) and coagulin Q (16) showed significant neurite outgrowth activity at a concentration of 1 microM on a human neuroblastoma SH-SY5Y cell line.
PMID: 12045329 [PubMed - indexed for MEDLINE]
[/quote]
Another herb that might have some potential to repair (or protect) damaged neural networks in mice and rats is Centella asiatica (Gotu Kola).
In vivo evidence:
[quote]
Physiol Behav. 2005 Nov 15;86(4):449-57. Epub 2005 Oct 6.
Centella asiatica treatment during postnatal period enhances learning and memory in mice.
Rao SB, Chetana M, Uma Devi P.
Department of Radiobiology, Kasturba Medical College, Manipal 576104, India.
Present investigation was planned to evaluate the nootropic effect of Centella asiatica. Three months old male Swiss albino mice were injected orally with graded doses (200, 500, 700, 1000 mg/kg body weight) of C. asiatica aqueous extract for 15 days to select an effective dose for nootropic studies. Animals were tested in radial arm maze to assess the learning and memory performance. Based on these results, mice were treated orally with 200 mg/kg of C. asiatica for 15 days from day 15 to day 30 post partum (p.p.) and the nootropic effect was evaluated on the 31st day and 6 months p.p. The behavioral (open field, dark/bright arena, hole board and radial arm maze tests), biochemical (acetylcholine esterase activity) and histological studies (dendritic arborization) were carried out. Performance of juvenile and young adult mice was significantly improved in radial arm maze and hole board tests, but locomotor activity did not show any change compared to control. Treatment resulted in increased acetylcholine esterase activity in the hippocampus. Dendritic arborization of hippocampal CA3 neurons was also increased in terms of intersections and branching points, both at one month and 6 months. Results of the present investigation show that treatment during postnatal developmental stage with C. asiatica extract can influence the neuronal morphology and promote the higher brain function of juvenile and young adult mice.
PMID: 16214185 [PubMed - in process]
[/quote]
[quote]
Evid Based Complement Alternat Med. 2006 Sep;3(3):349-57.
Centella asiatica (L.) Leaf Extract Treatment During the Growth Spurt Period Enhances Hippocampal CA3 Neuronal Dendritic Arborization in Rats.Mohandas Rao KG, Muddanna Rao S, Gurumadhva Rao S.
Centella asiatica (CeA) is a creeping plant growing in damp places in India and other Asian countries. The leaves of CeA are used for memory enhancement in the Ayurvedic system of medicine, an alternative system of medicine in India. In this study, we have investigated the effect during the rat growth spurt period of CeA fresh leaf extract treatment on the dendritic morphology of hippocampal CA3 neurons, one of the regions of the brain concerned with learning and memory. Neonatal rat pups (7 days old) were fed with 2, 4 or 6 ml kg(-1) body weight of fresh leaf extract of CeA for 2, 4 or 6 weeks. After the treatment period the rats were killed, their brains were removed and the hippocampal neurons were impregnated with silver nitrate (Golgi staining). Hippocampal CA3 neurons were traced using a camera lucida, and dendritic branching points (a measure of dendritic arborization) and intersections (a measure of dendritic length) were quantified. These data were compared with data for age-matched control rats. The results showed a significant increase in the dendritic length (intersections) and dendritic branching points along the length of both apical and basal dendrites in rats treated with 4 and 6 ml kg(-1) body weight per day of CeA for longer periods of time (i.e. 4 and 6 weeks). We conclude that the constituents/active principles present in CeA fresh leaf extract have a neuronal dendritic growth stimulating property; hence, the extract can be used for enhancing neuronal dendrites in stress and neurodegenerative and memory disorders.
PMID: 16951719 [PubMed - in process]
[/quote]
In vitro evidence:
[quote]
J Pharm Pharmacol. 2005 Sep;57(9):1221-9.
Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in-vitro.
Soumyanath A, Zhong YP, Gold SA, Yu X, Koop DR, Bourdette D, Gold BG.
Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland OR 97239, USA.
Axonal regeneration is important for functional recovery following nerve damage. Centella asiatica Urban herb, also known as Hydrocotyle asiatica L., has been used in Ayurvedic medicine for centuries as a nerve tonic. Here, we show that Centella asiatica ethanolic extract (100 microg mL-1) elicits a marked increase in neurite outgrowth in human SH-SY5Y cells in the presence of nerve growth factor (NGF). However, a water extract of Centella was ineffective at 100 microg mL-1. Sub-fractions of Centella ethanolic extract, obtained through silica-gel chromatography, were tested (100 microg mL-1) for neurite elongation in the presence of NGF. Greatest activity was found with a non-polar fraction (GKF4). Relatively polar fractions (GKF10 to GKF13) also showed activity, albeit less than GKF4. Thus, Centella contains more than one active component. Asiatic acid (AA), a triterpenoid compound found in Centella ethanolic extract and GKF4, showed marked activity at 1 microM (microg mL-1). AA was not present in GKF10 to GKF13, further indicating that other active components must be present. Neurite elongation by AA was completely blocked by the extracellular-signal-regulated kinase (ERK) pathway inhibitor PD 098059 (10 microM). Male Sprague-Dawley rats given Centella ethanolic extract in their drinking water (300-330 mg kg-1 daily) demonstrated more rapid functional recovery and increased axonal regeneration (larger calibre axons and greater numbers of myelinated axons) compared with controls, indicating that the axons grew at a faster rate. Taken together, our findings indicate that components in Centella ethanolic extract may be useful for accelerating repair of damaged neurons.
PMID: 16105244 [PubMed - in process]
[/quote]
Potential neuron protection properties:
[quote]
Res Commun Mol Pathol Pharmacol. 2000 Jul-Aug;108(1-2):75-86.
Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity.
Lee MK, Kim SR, Sung SH, Lim D, Kim H, Choi H, Park HK, Je S, Ki YC.
College of Pharmacy, Seoul National University, Korea.
Asiatic acid, a triterpene of Centella asiatica (L.) Urban (Umbelliferae), has been patented as a treatment for dementia and an enhancer of cognition by the Hoechst Aktiengesellschaft (EP 0 383 171 A2). We modified the chemical structure of asiatic acid and obtained 36 derivatives of asiatic acid in an attempt to prepare neuroprotective compounds that were more efficacious than asiatic acid itself. The neuroprotective activities of these derivatives were evaluated using primary cultures of rat cortical neurons insulted with the neurotoxin, glutamate, as an in vitro screening system. Among the semi-synthesized derivatives, three derivatives significantly mitigated the neurotoxicity induced by glutamate in this screening system. The neuroprotective activities of these 3 derivatives appeared to be more powerful than that of asiatic acid itself. These 3 derivatives significantly attenuated decreases in the levels of glutathione, glutathione peroxidase and other enzymes, which participate in the cellular defense mechanisms blunting oxidative stress. Furthermore, they significantly reduced the overproduction of NO induced by glutamate. These results showed that these derivatives of asiatic acid exerted significant neuroprotective effects on cultured cortical cells by their potentiation of the cellular oxidative defense mechanism. Therefore, these agents may prove to be efficacious in protecting neurons from the oxidative damage caused by exposure to excess glutamate.
PMID: 11758977 [PubMed - indexed for MEDLINE]
[/quote]
What is probably the best thing for anyone that may have comprised dopaminergic systems (including recovering opiate addicts) is exercise! There is much peer reviewed literature that suggests that exercise not only induces neurogenesis and has beneficial effects on neuroplasticity; but excercise also seems to have some antidepressant and "anti aging" effects...
The abstracts:
[quote]
J Psychiatry Neurosci. 2006 Mar;31(2):84-92.
Antidepressant effects of exercise: evidence for an adult-neurogenesis hypothesis?
* Ernst C,
* Olson AK,
* Pinel JP,
* Lam RW,
* Christie BR.
Neuroscience Program, UBC Hospital, University of British Columbia, Vancouver, BC.
It has been hypothesized that a decrease in the synthesis of new neurons in the adult hippocampus might be linked to major depressive disorder (MDD). This hypothesis arose after it was discovered that antidepressant medications increased the synthesis of new neurons in the brain, and it was noted that the therapeutic effects of antidepressants occurred over a time span that approximates the time taken for the new neurons to become functional. Like antidepressants, exercise also increases the synthesis of new neurons in the adult brain: a 2-3-fold increase in hippocampal neurogenesis has been observed in rats with regular access to a running wheel when they are compared with control animals. We hypothesized, based on the adult-neurogenesis hypothesis of MDD, that exercise should alleviate the symptoms of MDD and that potential mechanisms should exist to explain this therapeutic effect. Accordingly, we evaluated studies that suggest that exercise is an effective treatment for MDD, and we explored potential mechanisms that could link adult neurogenesis, exercise and MDD. We conclude that there is evidence to support the hypothesis that exercise alleviates MDD and that several mechanisms exist that could mediate this effect through adult neurogenesis.
PMID: 16575423 [PubMed - indexed for MEDLINE]
[/quote]
[quote]
Curr Alzheimer Res. 2006 Feb;3(1):49-54.
Environment, physical activity, and neurogenesis: implications for prevention and treatment of Alzhemier's disease.
* Briones TL.
Department of Medical-Surgical Nursing, University of Illinois, Chicago, IL 60612, USA. tbriones@uic.edu
Age is the biggest risk factor for the development of neurodegenerative diseases. Consequently, as the population ages it becomes more critical to find ways to avoid the debilitating cost of neurodegenerative diseases such as Alzheimer's. Some of the non-invasive strategies that can potentially slow down the mental decline associated with aging are exercise and use of multi-sensory environmental stimulation. The beneficial effects of both exercise and multi-sensory environmental stimulation have been well-documented, thus it is possible that these strategies can either provide neuroprotection or increase resistance to the development of age-related cognitive problems.
PMID: 16472203 [PubMed - indexed for MEDLINE]
[/quote]
[quote]
Neurobiol Aging. 2002 Sep-Oct;23(5):941-55
Exercise, experience and the aging brain.
* Churchill JD,
* Galvez R,
* Colcombe S,
* Swain RA,
* Kramer AF,
* Greenough WT.
Beckman Institute, University of Illinois at Urbana-Champaign, 405 N Mathews, Urbana, IL 61801, USA.
While limited research is available, evidence indicates that physical and mental activity influence the aging process. Human data show that executive functions of the type associated with frontal lobe and hippocampal regions of the brain may be selectively maintained or enhanced in humans with higher levels of fitness. Similarly enhanced performance is observed in aged animals exposed to elevated physical and mental demand and it appears that the vascular component of the brain response may be driven by physical activity whereas the neuronal component may reflect learning. Recent results have implicated neurogenesis, at least in the hippocampus, as a component of the brain response to exercise, with learning enhancing survival of these neurons. Non-neuronal tissues also respond to experience in the mature brain, indicating that the brain reflects both its recent and its longer history of experience. Preliminary measures of brain function hold promise of increased interaction between human and animal researchers and a better understanding of the substrates of experience effects on behavioral performance in aging. Copyright 2002 Elsevier Science Inc.
PMID: 12392797 [PubMed - indexed for MEDLINE]
[/quote]
[quote]
Trends Neurosci. 2002 Jun;25(6):295-301
Exercise: a behavioral intervention to enhance brain health and plasticity.
* Cotman CW,
* Berchtold NC.
Institute for Brain Aging and Dementia, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4540, USA. cwcotman@uci.edu
Extensive research on humans suggests that exercise could have benefits for overall health and cognitive function, particularly in later life. Recent studies using animal models have been directed towards understanding the neurobiological bases of these benefits. It is now clear that voluntary exercise can increase levels of brain-derived neurotrophic factor (BDNF) and other growth factors, stimulate neurogenesis, increase resistance to brain insult and improve learning and mental performance. Recently, high-density oligonucleotide microarray analysis has demonstrated that, in addition to increasing levels of BDNF, exercise mobilizes gene expression profiles that would be predicted to benefit brain plasticity processes. Thus, exercise could provide a simple means to maintain brain function and promote brain plasticity.
PMID: 12086747 [PubMed - indexed for MEDLINE]
[/quote]
[quote]
Brain Res. 2000 Dec 15;886(1-2):47-53
Neuroprotective signaling and the aging brain: take away my food and let me run.
* Mattson MP.
Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, 21224-6825, Baltimore, MD, USA. mattsonm@grc.nia.nih.gov
It is remarkable that neurons are able to survive and function for a century or more in many persons that age successfully. A better understanding of the molecular signaling mechanisms that permit such cell survival and synaptic plasticity may therefore lead to the development of new preventative and therapeutic strategies for age-related neurodegenerative disorders. We all know that overeating and lack of exercise are risk factors for many different age-related diseases including cardiovascular disease, diabetes and cancers. Our recent studies have shown that dietary restriction (reduced calorie intake) can increase the resistance of neurons in the brain to dysfunction and death in experimental models of Alzheimer's disease, Parkinson's disease, Huntington's disease and stroke. The mechanism underlying the beneficial effects of dietary restriction involves stimulation of the expression of 'stress proteins' and neurotrophic factors. The neurotrophic factors induced by dietary restriction may protect neurons by inducing the production of proteins that suppress oxyradical production, stabilize cellular calcium homeostasis and inhibit apoptotic biochemical cascades. Interestingly, dietary restriction also increases numbers of newly-generated neural cells in the adult brain suggesting that this dietary manipulation can increase the brain's capacity for plasticity and self-repair. Work in other laboratories suggests that physical and intellectual activity can similarly increase neurotrophic factor production and neurogenesis. Collectively, the available data suggest the that dietary restriction, and physical and mental activity, may reduce both the incidence and severity of neurodegenerative disorders in humans. A better understanding of the cellular and molecular mechanisms underlying these effects of diet and behavior on the brain is also leading to novel therapeutic agents that mimick the beneficial effects of dietary restriction and exercise.
PMID: 11119686 [PubMed - indexed for MEDLINE]
[/quote]
[quote]
Prog Neurobiol. 2004 Feb;72(3):167-82
Recovery from brain injury in animals: relative efficacy of environmental enrichment, physical exercise or formal training (1990-2002).
* Will B,
* Galani R,
* Kelche C,
* Rosenzweig MR.
Laboratoire de Neurosciences Comportementales et Cognitives, Institut Federatif des Neurosciences, Universite Louis Pasteur, UMR 7521, CNRS, Strasbourg, France. bruno.will@psycho-ulp.u-strasbg.fr
In the 1960s, it was shown for the first time that enriched housing enhances functional recovery after brain damage. During the 1970s and 1980s, many findings similar to this initial one have been reported, enlarging greatly its generality. Over the last 13 years, many different kinds of brain damage were modelled in animals or even directly studied in humans. Overall, these recent studies corroborated earlier findings, although occasional exceptions were reported. Other critical data, obtained mainly in intact animals, showed that enriched housing increases neurogenesis in the adult hippocampus. Recent evidence that this neurogenesis is involved in hippocampal-dependent learning supports the original interpretation of the enrichment effects as being the result of an accumulation of informal learning experiences (e.g., [. Heredity, environment, brain biochemistry, and learning. In: Current Trends in Psychological Theory. University of Pittsburgh Press, Pittsburgh, pp. 87-110;. Brain changes in response to experience. Sci. Am. 226, 22-29]). Other components of enriched environment, such as physical exercise, may have additive effects with those of training. The comparison of the relative effectiveness of enriched experience, of physical exercise and of training on structural and/or functional assessments of recovery, shows that training/learning is generally more effective than physical exercise and that enriched experience is a more potent therapy than either of these two other treatments. The combination of enriched experience with some other neurosurgical and/or neuropharmacological treatments may further improve its therapeutic effectiveness. Finally, other recent reports emphasize that the treatment parameters may be changed in order to approximate clinical/rehabilitation conditions and, nevertheless, remain effective. Copyright 2004 Elsevier Ltd.
PMID: 15130708 [PubMed - indexed for MEDLINE]
[/quote]
[quote]
Prog Brain Res. 2000;127:35-48
Activity-dependent regulation of neuronal plasticity and self repair.
* Kempermann G,
* van Praag H,
* Gage FH.
Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Plasticity is an essential characteristic of the brain: it is part of how the brain functions and is continuous while the brain interacts with the outer world. The state of activation and the level of activity of the entire organism affect the brain's plastic response. Brain plasticity has many substrates, ranging from synapses to neurites and entire cells. The production of new neurons is part of plasticity even in the adult and old brain, but under normal conditions neurogenesis only occurs in two privileged regions of the adult brain: hippocampus and olfactory system. [b]At least in the hippocampus, physical activity stimulates neurogenesis by acting on the proliferation of neuronal stem cells. More specific functions such as learning may be able to recruit new neurons from the pool of cells with neurogenic potential. In a broader context neuronal stem cells can likely be found throughout the brain. Therefore, novel approaches to neuroregeneration will, when most effective, make use of the activity-related effects on neuronal stem cells in the adult brain to activate these stem cells in a targeted manner to enhance brain function.
PMID: 11142036 [PubMed - indexed for MEDLINE]
[/quote]
However, you should work with a physician to ensure that taking any drug or supplement does not have any possible interactions or side effects with anything else you may be taking...or if you are allergic...and I think it's probably safest to get a subscription to Consumerlab.com -- and only choose brands that consistently pass their independent testing.
Take care.
