The deletion of the microtubule-associated STOP protein affects the serotonergic mouse brain network.
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.
INSERM UMRS 952, CNRS UMR 7224, Université Pierre et Marie Curie, Paris, France.
Vincent
V
Fournet
Marion
M
Jany
Véronique
V
Fabre
Farah
F
Chali
Didier
D
Orsal
Annie
A
Schweitzer
Annie
A
Andrieux
Fany
F
Messanvi
Bruno
B
Giros
Michel
M
Hamon
Laurence
L
Lanfumey
Jean-Christophe
JC
Deloulme
Marie-Pascale
MP
Martres
D000818:Animals; D001921:Brain / Q000502:physiology*; D005260:Female; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics*; D009415:Nerve Net / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse; D012701:Serotonin