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Medical Forum / General / Nutrition / June 2006Brain-Derived Neurotrophic Factor / Ampakines
...OR "Where Are My Ampakines?" Try not to flame me for being too lazy to exercise. But where are our long awaited Ampakines? (Any next best things - besides, you know - that exercise thing?) Look up the marketing blurbs, said to improve memory in rats. Couldpossibily help you to remember that there is no substitute for exercise in good health. out...@citynet.net wrote: > Look up the marketing blurbs, said to improve memory in rats. > Couldpossibily help you to remember that there is no substitute for > exercise in good health. No Kidding! I simply hoped to find a safe and effective way to reverse deterioation of Synaptic Plasticity and desterbances to long term potentiation in the Hippocampus. What I turned up is SCARY and from citations below. "As LTP is associated with calpain activation and spectrin degradation, we determined the effects of ampakine treatment of cultured hippocampal slices on spectrin degradation. Calpain activation was evaluated by determining the levels of the 145-150kDa degradation products of spectrin. Our data indicated that incubation of hippocampal slices with positive modulators of AMPA receptors resulted in enhanced spectrin degradation, an effect that was blocked by a calpain inhibitor. In addition, an antagonist of AMPAr but not of NMDAr blocked ampakine-induced spectrin degradation. These results indicate that prolonged treatment with selected ampakines leads to spectrin degradation mediated by activation of the calcium-dependent protease calpain." "Prolonged exposure of cultured hippocampal slices to CX614 [2H,3H,6aH-pyrrolidino[2'',1''-3',2']1,3-oxazino[6',5'-5,4]-benzo[e]1,4-dioxan 10-one], a positive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAr) modulator, decreases receptor response to synaptic stimulation, an effect that could reflect reduced receptor expression....We conclude that CX614-induced AMPAr protein loss is primarily mediated by AMPAr activation and involves calpain-dependent proteolysis of SAP97 and GRIP1." 1: Jourdi H, Yanagihara T, Martinez U, Bi X, Lynch G, Baudry M. Effects of positive AMPA receptor modulators on calpain-mediated spectrin degradation in cultured hippocampal slices. Neurochem Int. 2005 Jan;46(1):31-40. PMID: 15567513 [PubMed - indexed for MEDLINE] 2: Jourdi H, Lu X, Yanagihara T, Lauterborn JC, Bi X, Gall CM, Baudry M. Prolonged positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors induces calpain-mediated PSD-95/Dlg/ZO-1 protein degradation and AMPA receptor down-regulation in cultured hippocampal slices. J Pharmacol Exp Ther. 2005 Jul;314(1):16-26. Epub 2005 Mar 22. PMID: 15784649 [PubMed - indexed for MEDLINE] OK - so exercise asside... I am very open to suggestions. What might be some safe and effective way to reverse deterioration of Synaptic Plasticity and disturbances to Long Term Potentiation in the Hippocampus? > What might be some safe and effective way to reverse deterioration > of Synaptic Plasticity and disturbances to Long Term Potentiation in > the Hippocampus? I ask that because it is one common problem we see in: Age Related Dementia, PTSD, Stimulant abuse and Depression. The basic science suggests numerous mechanisms (including promoting glutamate receptor, cAMP, or CREB function, as three examples). The challenge is knowing what molecules - then getting the molecules into human brains - without doing more harm than good. Thanks for the help - this is SO over my head! It appears that pyrrolidone derivatives fit the description like Piracetam. > It appears that pyrrolidone derivatives fit the description like > Piracetam. Yes - I came upon Aniracetam (and a phosphodiesterase inhibitor called Rolipram) 98% of the basic science lit seems to encourage increasing cAMP response AND AMPA transmission. Sadly - 2% suggests that this is at least as neuro / excito-toxic as benificial. This is seriously complicated suff! What Glutamenergic sub systems do we activate - and which do we put the breaks on? I am still working on it... Warm Regards, - Zevon The Big Question: Simply - in abstinent, former long term substance abusers - how might a clinician treat or reverse the 'frontal lobe' type dysfunctions and anhedonia? This all started by my asking a few professionals - the following - regarding potential agents for reversing identical damage that we see in ALL of the following: Stimulant Abuse, PTSD, Age Related Dementia and Depression. I asked: What might be some safe and effective way to reverse deterioration of Synaptic Plasticity and disturbances to Long Term Potentiation in the Hippocampus? I was given 3 great examples: "Promoting glutamate receptor, cAMP, or CREB function". I was told that: Both a cAMP phosphodiesterase inhibitor and an alpha-amino-3-hydroxy-5-methylisoxazole propionate (AMPA) potentiator were suggested to somehow 1) Enhance Neuronal plasticity and / or cellular resilience AND / OR 2) Provide mitochondrial support / conserving growth factor receptors It sounded good - until I came across a few articles regarding hyper glutaminergic activity in drug addicts. Long term Cocaine abusers do such damage to their glutaminergic system that as another researcher put it: "CONCLUSIONS: Cellular adaptations in prefrontal glutamatergic innervation of the accumbens promote the compulsive character of drug seeking in addicts by decreasing the value of natural rewards, diminishing cognitive control (choice), and enhancing glutamatergic drive in response to drug-associated stimuli." Stay with me - I am getting to the question. Forgive me, I have now been reading too much basic science on reversing the long term neurological damage done by many years of substance abuse. I have seen hopeful pharmacological treatments proposed to: * Decrease the motivational value of the drug or * Inhibit conditioned responses to stimuli predicting drug availability. I have seen nothing proposed to * Increase the motivational value of nondrug reinforcers or to * Improve frontal lobe dysfunction. Simply - in abstinent, former long term substance abusers - how might a clinician treat or reverse the 'frontal lobe' type dysfunctions and anhedonia? (this is not only the direct result of abuse - but further perpetuates the addiction) What do I have to show for it? Only one potential agent: N-acetylcysteine. All the AMPAkine type products stimulate drug craving. Thank you so very much! Warmest Regards, - Zevon > What do I have to show for it? > Only one potential agent: > N-acetylcysteine. So, it seems reasonable. Give it a try. It can't hurt anywhere as much as the drugs that fried you to begin with. Maybe try CES (cranio-electrostimulation). > The Big Question: > [quoted text clipped - 71 lines] > Warmest Regards, > - Zevon Heck, if you're going to follow that tact, then why not see a therapist for EMDR? > Maybe try CES (cranio-electrostimulation). > [quoted text clipped - 73 lines] > > Warmest Regards, > > - Zevon what is emdr. > Heck, if you're going to follow that tact, then why not see a therapist for > EMDR? [quoted text clipped - 76 lines] > > > Warmest Regards, > > > - Zevon Go visit EMDRIA.org . Eye Movement Desensitization and Reprogramming. Basically, traumatic events are brought near the surface then the therapist uses finger or buzzer in each of your hands and or lights (Las Vagas style) moving from left to right, perhaps music with beats or change in volume moving as well. The whole idea is that trauma has not been processed. When you see a wild animal or even your pet get over a trauma, they go through a certain pattern, which, incidently involves the tracking of the eyes and head and shaking it off. Traumas can be resolved very quickly without having to be relived. Or rather they are relived deep below the surface. There are two types of traumas. The big T (I was in a car accident) and the little t (my parents constantly told me I was no good and would never amount to anything). I see the drug exhaustion as a little t. These take a longer time to treat but can be treated. > what is emdr. Then there's the Cell Phone. http://www.cnn.com/2006/TECH/ptech/06/26/cellphones.brain.reut/index.html |
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