In article ,
C.Evelo at Farmaco.Unimaas.nl wrote:
>> Christopher Hatton wrote:
> >
> > Eva, this is my question also, I'm wondering if its involved in
> > corticosteroid control which might also be of interest to nutrionlists,
> > but also possible a possible neuroprotective affect against Ischaemia.
> > However I keep drawing blanks, it seems that this and other newsgroups
> > don't have the readers we need to answer our questions.
> > Christopher Hatton
> > BL- Institut für Neurobiologie
>> What would the mechanism for such a neuroprotective effect be?
>> Chris Evelo
Well Chris (and others)
I really don't really know where to start but this might help,
Prog Neuropsychopharmacol Biol Psychiatry 21 (1): 69-102 (1997)
Neuroprotective and anti-amnesic potentials of sigma (sigma) receptor
ligands
Maurice T, Lockhart BP
... Snipped.. The sigma 1 ligands prevent the experimental amnesia
induced by muscarinic cholinergic antagonists at either the learning,
consolidation or retention phase of the mnesic process. This effect
involves a potentation of acetylcholine release induced by sigma 1
ligands selectively in the hippocampal formation and cortex . 4. The
sigma 1 receptor ligands also attenuate the learning impairment induced
by dizocilpine, a non-competitive antagonist of the NMDA receptor, and
may relate to the potentiating effect of sigma 1 ligands on several NMDA
receptor-mediated responses previously described in vitro and in vivo in
the hippocampus. This effect is shared by NPY- and CGRP-related peptides
and by neuroactive steroids, confirming the in vitro evidences of
functional interactions between the sigma 1 receptors and these different
systems.
There was also something presented last year at the Americam Neuroscience
meeting in Washington last year about neuroprotective effects of female
sex hormones, and that in men as they get old Progesterone or Oestrodial
levels fall off quickly in the hippocampus and thus hypothesis is that
men are more prone to ischaemic damage in hippocampus, Infact this is
one of the reasons that we use male mongolian gerbils in our ischaemia
model.. As female are more resistant to CA1 neuronal death.
My theory is that this Cyto. P450 CYP7B helps keep the levels of
neurosteroids up in the hippocampus, it is also possible that these
neurosteroids just might also act at the GABA-A receptor and help keep
the levels of glutamate (and aspartate down) during an annoxic episode
although maybe not of much help if prolonged hypoglycaemia also.
I realise that there are a lot of sweeping statements in there, but after
all I am only a PhD student also quite new to neuroscience, although my
BSc was in Toxicology. For me, many people rubbished the idea of P450's
in the hippocampus having an important role, it appears that Cyt. P450's
and other enzymes systems have a role in the blood-brain barrier
endothelial cell (which are also quite resistant to hypoxia).
Whilst there has been much talk of cognitive function and LTP of
neurosteroids, it may also be that they also either purposely or
indirectly protect the neurones from excess stress. Of course if some one
can proof conclusisly that Cyto. P450's in the hippocampus have no direct
effect on neuronal survival after ischaemia then I'll drop my theory.
yours
Christopher Hatton
BL-Institute for Neurobiology
(learning and memory processes)
Magdeburg
Germany
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