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.
Int J Neuropsychopharmacol. 2013 Apr;16(3):683-9. doi: 10.1017/S1461145712000879. Epub 2012 Sep 11.
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.
周期蛋白依赖性激酶 5（CDK5）和 p35/p25 激活剂与胞吐机制（例如 munc18-1 和 syntaxin-1A）相互作用，在神经分泌中发挥关键作用。本研究旨在研究精神分裂症（SZ）和重度抑郁症（MD）患者死后前额叶皮层（PFC）/布罗德曼 9 区（Brodmann's area 9）中 CDK5/p35/p25 的基础状态和精神药物的作用（在血液/尿液样本中检测到）。在 SZ 患者中（所有患者，n = 24），与对照组相比，CDK5 和 p35 减少（-28%至-58%），但 p25 未减少。在 SZ 未接受抗精神病药物治疗的患者中（n = 12），激活剂 p35 减少（-52%）。在 SZ 接受抗精神病药物治疗的患者中（n = 12），定量检测到 CDK5（-47%）、p35（-76%）和 p25（-36%）明显减少。在 MD 患者中（n = 13），包括未接受/接受抗抑郁药物治疗的亚组，CDK5、p35 和 p25 均未改变。在 SZ 患者中（n = 24），CDK5、p35 或 p25 与 munc18-1a 相关，但与 syntaxin-1A 无关。研究结果表明，p35 的基础含量减少和抗精神病药物对 SZ 中 CDK5/p35/p25 的下调。提示的 CDK5/munc18-1a 功能相互作用可能导致 SZ PFC 中神经分泌失调。
