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Olivier Manzoni, Marja Sepers |
Olivier Manzoni, PhD, Principal Investigator
Marja Sepers, PhD, Postdoctoral Fellow
INSERM
Bordeaux, France
FRAXA Awards:
$45,000 in 2009
This team is examining abnormalities in the endocannabinoid system - pathways in the brain which are stimulated by
cannabinoids like marijuana or THC - in Fragile X.
This is a promising approach because drugs currently in development could correct this dysfunction.
by Olivier Manzoni, 5/2009
The present study proposes an extension to the mGluR hypothesis since a major function of group I mGluR
is to make endocannabinoids. In this regard, it is surprising that the endocannabinoid system has never
been studied in the context of fragile X syndrome. To that end we will address the following hypothesis.
HYPOTHESIS: Following mGluR5 dysregulation in FMR1 null mice, activity dependent synaptic plasticity
in the nucleus accumbens is disrupted due to aberrant endocannabinoid signalling, which
can be modulated to rescue synaptic function.
Marijuana has been used medicinally for centuries. The most distressing side effect when used as
an antiemetic by patients in chemotherapy has been the "high" or psychotropic effect. The eCB
system is an attractive potential therapeutic target for fragile X syndrome because CB1R overlaps
with mGluR5 throughout the rat brain with high densities in the striatum, cortex and hippocampus
(Tsou et al., 1998; Romano et al., 1996). Drugs that target the enzymes of cannabinoid degradation
would affect only eCBs involved in synaptic signalling where they are released
and therefore bypass the system wide activation of CB1R responsible for unwanted psychotropic side effects.
more FRAXA research reports
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