Division of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK.
Division of Pharmacy and Optometry, University of Manchester, Manchester, UK.
J Psychopharmacol. 2020 Jan;34(1):115-124. doi: 10.1177/0269881119874446. Epub 2019 Oct 3.
Sub-chronic phencyclidine treatment (scPCP) provides a translational rat model for cognitive impairments associated with schizophrenia (CIAS). CIAS genetic risk factors may be more easily studied in mice; however, CIAS associated biomarker changes are relatively unstudied in the scPCP mouse.
To characterize deficits in object recognition memory and synaptic markers in frontal cortex and hippocampus of the scPCP mouse.
Female c57/bl6 mice received 10 daily injections of PCP (scPCP; 10 mg/kg, s.c.) or vehicle ( = 8/group). Mice were tested for novel object recognition memory after either remaining in the arena ('no distraction') or being removed to a holding cage ('distraction') during the inter-trial interval. Expression changes for parvalbumin (PV), glutamic acid decarboxylase (GAD67), synaptosomal-associated protein 25 (SNAP-25) and postsynaptic density 95 (PDS95) were measured in frontal cortex, dorsal and ventral hippocampus.
scPCP mice showed object memory deficits when distracted by removal from the arena, where they treated previously experienced objects as novel at test. scPCP significantly reduced PV expression in all regions and lower PSD95 levels in frontal cortex and ventral hippocampus. Levels of GAD67 and SNAP-25 were unchanged.
We show for the first time that scPCP mice: (a) can encode and retain object information, but that this memory is susceptible to distraction; (b) display amnesia after distraction; and (c) express reduced PV and PSD95 in frontal cortex and hippocampus. These data further support reductions in PV-dependent synaptic inhibition and NMDAR-dependent glutamatergic plasticity in CIAS and highlight the translational significance of the scPCP mouse.
亚慢性苯环己哌啶（PCP）处理（scPCP）为与精神分裂症相关的认知障碍（CIAS）提供了一种转化大鼠模型。CIAS 的遗传风险因素可能更容易在小鼠中研究；然而，scPCP 小鼠中与 CIAS 相关的生物标志物变化相对较少研究。
描述 scPCP 小鼠前额叶皮层和海马体中物体识别记忆和突触标志物的缺陷。
雌性 c57/bl6 小鼠接受 10 天的 PCP（scPCP；10mg/kg，皮下注射）或载体（每组 8 只）注射。在试验间隔期间，无论在竞技场中（“无干扰”）还是移至保持笼中（“干扰”），小鼠均接受新物体识别记忆测试。在前额叶皮层、背侧和腹侧海马体中测量钙结合蛋白（PV）、谷氨酸脱羧酶（GAD67）、突触相关蛋白 25（SNAP-25）和突触后密度 95（PDS95）的表达变化。
scPCP 小鼠在从竞技场中移走时表现出物体记忆缺陷，在测试中它们将之前经历过的物体视为新物体。scPCP 显著降低了所有区域的 PV 表达，并降低了前额叶皮层和腹侧海马体中的 PSD95 水平。GAD67 和 SNAP-25 的水平没有变化。
我们首次表明，scPCP 小鼠：（a）能够编码和保留物体信息，但这种记忆容易受到干扰；（b）在干扰后表现出健忘症；（c）在前额叶皮层和海马体中表达减少的 PV 和 PSD95。这些数据进一步支持 CIAS 中 PV 依赖性抑制和 NMDAR 依赖性谷氨酸能可塑性的减少，并突出了 scPCP 小鼠的转化意义。
