瑞士Friedrich Miescher研究所Pico Caroni团队发现小鼠精神分裂症模型中改善神经网络与认知失调的新治疗策略。2019年8月29日，《细胞》在线发表了这一最新研究成果。

研究人员证明成年LgDel ^+/-小鼠（精神分裂症的遗传模型）表现出小白蛋白（PV）神经元低招募以及相关的慢性PV神经元可塑性以及网络和认知的缺陷。所有这些缺陷都可以通过PV神经元的化学激活或D2R拮抗剂治疗永久性地挽救，特别是针对青春期晚期敏感时间窗口期的腹侧海马（vH）或内侧-前额叶皮质中。PV神经元改变最初局限于海马区的CA1/下托部位，在那里它们对青春期后期的治疗有反应。因此，在青春期后期的敏感时间窗口期，通过增强vH-mPFC PV网络功能的治疗可以预防精神分裂症模型小鼠的疾病进展，这为预防精神分裂症爆发提供了治疗策略。

据介绍，尽管疾病敏感过程发生得更早，但精神分裂症在青年期被诊断出来，这表明它可能涉及易感个体中晚期大脑发育时的病理转变。PV中间神经元改变已被发现，但它们在该疾病中的作用尚不清楚。

附：英文原文

Title: Long-Lasting Rescue of Network and Cognitive Dysfunction in a Genetic Schizophrenia Model

Author: Arghya Mukherjee, Fernando Carvalho, Stephan Eliez, Pico Caroni

Issue&Volume: 29 August 2019

Abstract: Although sensitizing processes occur earlier, schizophrenia is diagnosed in young adulthood, which suggests that it might involve a pathological transition during late brain development in predisposed individuals. Parvalbumin (PV) interneuron alterations have been noticed, but their role in the disease is unclear. Here we demonstrate that adult LgDel +/ mice, a genetic model of schizophrenia, exhibit PV neuron hypo-recruitment and associated chronic PV neuron plasticity together with network and cognitive deficits. All these deficits can be permanently rescued by chemogenetic activation of PV neurons or D2R antagonist treatments, specifically in the ventral hippocampus (vH) or medial-prefrontal cortex during a late-adolescence-sensitive time window. PV neuron alterations were initially restricted to the hippocampal CA1/subiculum, where they became responsive to treatment in late adolescence. Therefore, progression to disease in schizophrenia-model mice can be prevented by treatments supporting vH-mPFC PV network function during a sensitive time window late in adolescence, suggesting therapeutic strategies to prevent the outbreak of schizophrenia.

DOI: https://doi.org/10.1016/j.cell.2019.07.023

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30790-1#