The deletion of the microtubule-associated STOP protein affects the serotonergic mouse brain network. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Journal of Neurochemistry Year : 2010

The deletion of the microtubule-associated STOP protein affects the serotonergic mouse brain network.

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.
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Dates and versions

inserm-00566974 , version 1 (17-02-2011)

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Vincent Fournet, Marion Jany, Véronique Fabre, Farah Chali, Didier Orsal, et al.. The deletion of the microtubule-associated STOP protein affects the serotonergic mouse brain network.. Journal of Neurochemistry, 2010, 115 (6), pp.1579-94. ⟨10.1111/j.1471-4159.2010.07064.x⟩. ⟨inserm-00566974⟩
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