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Science Forum Index » Life Extension Forum » Do the glutamate excitotoxicity theory and potential...
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 Posted: Wed Jun 11, 2008 9:27 am |
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Encephale. 2002 Mar-Apr;28(2):147-53.Links
[Do the glutamate excitotoxicity theory and potential free radicals
implication in schizophrenia aetiopathogenesis provide a new
enlightenment to links between: genome, environment and biology in the
determinism of that disorder?][Article in French]
Nguimfack Mbodie PC.
md, Interne de Psychiatrie, Centre Hospitalier Spécialisé de
Psychiatrie, 22, rue de l'Hôpital, 56890 Saint-Ave, France.
The aetiopathogenesis of schizophrenia constitutes nowadays one of the
major points of interest for researchers on this cosmopolitan disorder
which involves about 1% of the world population and which
significantly alters the social functioning of the individual.
Numerous studies have focused on the role played by genome,
environmental factors and biology in the development of symptoms. The
neurodevelopmental theory is an illustration with the perinatal period
considered as the main provider of environmental factors
(hypertension, infections, bleedings during pregnancy, acute and
chronic fetal distress.). Many authors found significant associations
between such factors, the occurrence of brain lesions and finally
schizophrenic symptoms. Although no convincing genetic model had been
established to date for schizophrenia, nevertheless it appears that a
predisposition not inheritable under the mendelian mode exists and
authors showed that disease gets more and more severe over
schizophrenic descendants. The risk to be schizophrenic being a first
degree relative of the schizophrenic person is about ten time superior
than in general population. Indeed, this risk is also about ten time
superior in biological parents of schizophrenic adoptees than in
biological parents of healthy adoptees. Studies done in monozygotic
comparing to dizygotic twins are in favour of an important role played
by genetic factors more than socioeducational or psychological
factors. Concerning biology, the dopaminergic hypothesis remains
shared by numerous authors although direct links with incriminated
factors are not well established. Now is suspected the glutamate
excitotoxicity with implication of free radicals in schizophrenia.
These free radicals are products of various enzymatic activations led
by overstimulation of post synaptic receptors (NMDA and AMPA) by the
excess glutamate. Therefore, according to that concept, some amino
acids as glutamate and derivatives could have through free radicals a
noxious effect on neuronal synapses. This could be due to a failing of
their recapture at the presynaptic level in addition to a
dysfunctioning of the antioxidizing system (glutathion, carnosine,
superoxide dismutase, aspartate) to which dopamine and other
monoamines might participate. The question is whether or not this
theory contributes to shed light on links between: genome,
environmental factors and biology in schizophrenia. Through the review
and discussion of genetical aspects of schizophrenia, environmental
factors and the biological aspect, we intend to revive debate on that
question. The articles and authors were selected with regard to the
aptness of their publications on that subject, their evolving ideas
and finally the interest of their works for neurosciences. This new
approach perhaps is opening the way to new therapeutic perspectives in
the treatment of schizophrenia based on the antioxidizing substances
as shown for some neurological diseases (amyotrophic lateral
sclerosis, Parkinson's disease and Huntington's chorea) for which
experiments are going on.
PMID: 11972141 [PubMed - indexed for MEDLINE] |
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