Growth factors & repair of brain damage

[VelocideX]

What nerve growth factors does the brain have besides NGF and BDNF?

Do these have the potential to repair (either partially or fully) any brain damage incurred by drugs?

Could it partially repair MDMA neurotoxicity, were that to occur? What about generalised deterioration, such as from alcohol abuse?

I can't really phrase the question much better than that, due to my complete lack of understanding of how significant the effects of growth factor are....

I realise that growth factors don't pass the blood-brain barrier, but many drugs we know of currently cause the release of growth factors, either directly or indirectly.

 

[BilZ0r]

GDNF, IGF-1 basic fibroblast growth factor, Theres quite a lot really.. neurotrophins 1-4 (though I -think- 3 and 4 are the two real neurotrophins), neurturin, artemin and persephin... Though they're not really my thing.

Do a search for "Neuroprotection GDNF BDNF" on pubmed and you'll see a list of PRE-treatment with neurotrophic factors PROTECTING against neurotoxicity. Also, papers like this and this should be of interest... I don't know of any studies where they give the neurotrophic factors AFTER the neurotoxic insults.

 

[Riemann Zeta]

Alas, since trophic factors are peptides, there is no way of getting them across the BBB--one reason tests of IV/IM/SC growth factor administration have failed to show significant response in neurodegenenrative diseases. We need small-molecule nerve growth factor agonists.

 

[VelocideX]

Some things we know of seem to release growth factors. SSRIs cause an increase in BDNF. Is this their method of operation? I'm not sure, and I don't think anyone else is. Many of the so-called nootropics have associated articles which claim release of one growth factor or another...

Selegiline and desmethylselegiline stimulate NGF, BDNF, and GDNF synthesis in cultured mouse astrocytes.

Oral administration of idebenone, a stimulator of NGF synthesis, recovers reduced NGF content in aged rat brain.

 

[Lysergium]

...

 

[morphiquet]

each new experience releases neurotrophic factors, even your first binge with alcohol.
i think, that's the basis for all "neurotrophic thinking", but this simple fact often seems to be ignored.

 

[mad_scientist]

Nerve growth factors do cause proliferation of new neural stem cells in adults, mainly in the olfactory bulb, and these then migrate throughout the brain and differentiate into more specialised kinds of neurons depending on local conditions.

Most of the research has been done in rats and mice obviously, but im pretty sure there was evidence showing that it happens in humans as well, when i was at uni some of our lecturers were researching this process for potential applications in treating alzheimer's and parkinson's disease. Don't have refs on me though sorry my lecture notes are overseas...

Anyway they found a bunch of things which either stimulate or inhibit the production of nerve growth factors (mainly NGF, BDNF & GDNF) and these were shown to influence the rate and extent of neural stem cell production, also when neural stem cell production was inhibited it interfered with learning and memory, and when it was enhanced it improved learning and memory.

Things which stimulate nerve growth factor production were: environmental enrichment, calorie restriction, SSRIs, 5HT2A agonists and (strangely enough) CB1 agonists.

Things which inhibit nerve growth factor production were: excess calories, depression, amphetamines, opiates. Think nicotine and cocaine might have been on that list too.

So basically apart from environmental factors theres a lot of drugs that influence this system. Most recreational drugs inhibit nerve growth factor production, except for SSRIs, hallucinogens and cannabis which stimulate it.

And just to make it more complicated, cannabis has negative effects on memory, and nicotine has positive effects on memory, by mechanisms that are seperate from their influence on nerve growth factor production, so with those two drugs its difficult to predict which way the overall effect will go, probably depends on dosage etc.

 

[Dondante]

Things which stimulate nerve growth factor production were: environmental enrichment, calorie restriction, SSRIs, 5HT2A agonists and (strangely enough) CB1 agonists.

Could excessively high trophic factors cause abberant connections that could be counterproductive or even harmful? I've kinda wondered if the persistent visual phenomena of HPPD or other psychological problems associated with excessive 5-HT2A agonist intake could be due to abnormal connections being formed. For example, in the case of HPPD, there could be unregulated proliferation in the visual cortex, since the symptoms seem to persist so long. I've seen it proposed before that symptoms could be due to increased 5-HT sensitivity of inhibitory neurons in the claustrum and Layer 4 of V1. But why would increased sensitivity persist for years? I suppose it could be LTP and not just increased receptor numbers.

I don't know how influential neurotrophic factors are in the formation of new synapses, but something like large-scale proliferation of inhibitory connection in Layer 4 of V1 could cause problems with visual input. Just a thought ...

 

[mad_scientist]

^^^

Yeah my lecturers suggested that could be a mechanism contributing to HPPD.

Id suspect inappropriate over-strengthening of connections that are already there though rather than formation of brand new ones, mainly just because i would imagine it takes longer for new neural stem cells to proliferate, migrate and differentiate than the 18 hours or so LSD acts for. But who knows really...does HPPD typically result from multiple trips over time, or from one big one?

 

[Dondante]

In my experience, lasting visual phenomena from psychedelic use usually peaks about one to two weeks after the experience, and then slowly decline over many months. It's hard to say though, becuase so many things could affect that subjective interpretation.

Also, strengthening of synapses could be a combination of increased neurotrophic factors, increased 5-HT2A receptor density, and/or increased receptor sensitivity due to intracellular events. If new connections played a role, I wouldn't guess there'd be a relation to stem cell proliferation and migration (since that seems to be extremely minimal with the exception of the dentate gyrus I suppose). Existing neurons might be prompted to extend new axons and dendrites though.