期刊
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
卷 16, 期 3, 页码 683-689出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S1461145712000879
关键词
Antidepressants; antipsychotics; CDK5/p35/p25; major depression; schizophrenia
资金
- Ministerio de Economia y Competitividad (MINECO)
- Fondo Europeo de Desarrollo Regional (FEDER), Madrid, Spain
- RETICS, Red de Trastornos Adictivos [RD06/001/003]
- CIBERSAM
- Intramural Research Program
- Basque Government [IT-199/07, UPV/EHU (UFI 11/35)]
- RETICS-RTA
Cyclin-dependent kinase-5 (CDK5) and p35/p25 activators, interacting with the exocytotic machinery (e. g. munc18-1 and syntaxin-1A), play critical roles in neurosecretion. The basal status of CDK5/p35/p25 and the effect of psychotropic drugs (detected in blood/urine samples) were investigated in post-mortem prefrontal cortex (PFC)/Brodmann's area 9 of schizophrenia (SZ) and major depression (MD) subjects. In SZ (all subjects, n=24), CDK5 and p35, but not p25, were reduced (-28 to -58%) compared to controls. In SZ antipsychotic-free (n=12), activator p35 was decreased (-52%). In SZ antipsychotic-treated (n=12), marked reductions of CDK5 (-47%), p35 (-76%) and p25 (-36%) were quantified. In MD (n=13), including antidepressant-free/treated subgroups, CDK5, p35 and p25 were unaltered. In SZ (n=24), CDK5, p35 or p25 correlated with munc18-1a, but not with syntaxin-1A. The results demonstrate reduced p35 basal content and down-regulation of CDK5/p35/p25 by antipsychotics in SZ. The suggested CDK5/munc18-1a functional interaction may lead to dysregulated neurosecretion in SZ PFC.
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