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The deletion of the microtubule-associated STOP protein affects the serotonergic

The deletion of microtubule-associated protein stable tubule only polypeptide (STOP) leads to neuroanatomical, biochemical and severe behavioral...

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    [title] => The deletion of the microtubule-associated STOP protein affects the serotonergic
    [paragraph] => The deletion of the microtubule-associated STOP protein affects the serotonergic mouse brain network. 
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Authors
V. Fournet, M. Jany, V. Fabre, F. Chali, D.  Orsal et al. 

 Lab
INSERM UMRS 952, CNRS UMR 7224, Université Pierre et Marie Curie, Paris, France.
Journal
Journal of Neurochemistry
Abstract
The deletion of microtubule-associated protein stable tubule only polypeptide (STOP) leads to neuroanatomical, biochemical and severe behavioral alterations in mice, partly alleviated by antipsychotics. Therefore, STOP knockout (KO) mice have been proposed as a model of some schizophrenia-like symptoms. Preliminary data showed decreased brain serotonin (5-HT) tissue levels in STOP KO mice. As literature data demonstrate various interactions between microtubule-associated proteins and 5-HT, we characterized some features of the serotonergic neurotransmission in STOP KO mice. In the brainstem, mutant mice displayed higher tissue 5-HT levels and in vivo synthesis rate, together with marked increases in 5-HT transporter densities and 5-HT1A autoreceptor levels and electrophysiological sensitivity, without modification of the serotonergic soma number. Conversely, in projection areas, STOP KO mice exhibited lower 5-HT levels and in vivo synthesis rate, associated with severe decreases in 5-HT transporter densities, possibly related to reduced serotonergic terminals. Mutant mice also displayed a deficit of adult hippocampal neurogenesis, probably related to both STOP deletion and 5-HT depletion. Finally, STOP KO mice exhibited a reduced anxiety- and, probably, an increased helpness-status, that could be because of the strong imbalance of the serotonin neurotransmission between somas and terminals. Altogether, these data suggested that STOP deletion elicited peculiar 5-HT disconnectivity.
BIOSEB Instruments Used
Tail Suspension Test - Wireless (BIO-TST5)
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