title: Cyclin-dependent kinase-5 and p35/p25 activators in schizophrenia and major depression prefrontal cortex: basal contents and effects of psychotropic medications.
abstract: 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.
authors.affiliation: Laboratorio de Neurofarmacología, IUNICS, Universitat de les Illes Balears and Redes Temáticas de Investigación Cooperativa en Salud-Red de Trastornos Adictivos, Palma de Mallorca, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ramos-Miguel
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Meana
authors.forename: Jesús A
authors.initials: JA
authors.lastname: García-Sevilla
mesh_terms: D000328:Adult; D000368:Aged; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011619:Psychotropic Drugs / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D009419:Nerve Tissue Proteins; D011619:Psychotropic Drugs; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human