Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
Department of Pharmacy, Peking University First Hospital, Beijing, China.
Transl Psychiatry. 2021 Feb 8;11(1):117. doi: 10.1038/s41398-021-01240-x.
Cognitive impairment is a core characteristic of schizophrenia, but its underlying neural mechanisms remain poorly understood. Reduced brain-derived neurotrophic factor (BDNF), a protein critical for neural plasticity and synaptic signaling, is one of the few molecules consistently associated with cognitive deficits in schizophrenia although the etiological pathway leading to BDNF reduction in schizophrenia is unclear. We examined microRNA-195 (miR-195), a known modulator of BDNF protein expression, as a potential mechanistic component. One-hundred and eighteen first-episode patients with schizophrenia either antipsychotic medication-naïve or within two weeks of antipsychotic medication exposure and forty-seven age- and sex-matched healthy controls were enrolled. MiR-195 and BDNF mRNA and BDNF protein levels in peripheral blood were tested. Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). MiR-195 was significantly higher (p = 0.01) whereas BDNF mRNA (p < 0.001) and protein (p = 0.016) levels were significantly lower in patients compared with controls. Higher miR-195 expression was significantly correlated to lower BDNF protein levels in patients (partial r = -0.28, p = 0.003) and lower BDNF protein levels were significantly associated with poorer overall cognitive performance by MCCB and also in speed of processing, working memory, and attention/vigilance domains composite score (p = 0.002-0.004). The subgroup of patients with high miR-195 and low BDNF protein showed the lowest level of cognitive functions, and miR-195 showed significant mediation effects on cognitive functions through BDNF protein. Elevated miR-195 may play a role in regulating BDNF protein expression thereby influencing cognitive impairments in schizophrenia, suggesting that development of cognition enhancing treatment for schizophrenia may consider a micro-RNA based strategy.
认知障碍是精神分裂症的核心特征，但其潜在的神经机制仍知之甚少。脑源性神经营养因子（BDNF）减少，这种蛋白质对神经可塑性和突触信号传递至关重要，是少数与精神分裂症认知缺陷一致相关的分子之一，尽管导致精神分裂症 BDNF 减少的病因途径尚不清楚。我们研究了 microRNA-195（miR-195），它是一种已知的 BDNF 蛋白表达调节剂，作为潜在的机制成分。我们招募了 118 名首发精神分裂症患者，这些患者要么未接受抗精神病药物治疗，要么在接受抗精神病药物治疗后两周内，以及 47 名年龄和性别匹配的健康对照者。检测了外周血中的 miR-195 和 BDNF mRNA 和 BDNF 蛋白水平。使用 MATRICS 共识认知电池（MCCB）评估认知功能。miR-195 显著升高（p=0.01），而 BDNF mRNA（p<0.001）和蛋白（p=0.016）水平在患者中显著降低与对照组相比。miR-195 表达越高，患者的 BDNF 蛋白水平越低（偏相关 r=-0.28，p=0.003），BDNF 蛋白水平越低，MCCB 的整体认知表现越差，以及在处理速度、工作记忆和注意力/警觉域综合评分方面（p=0.002-0.004）。miR-195 高和 BDNF 蛋白低的患者亚组认知功能最低，miR-195 通过 BDNF 蛋白对认知功能具有显著的中介作用。miR-195 升高可能在调节 BDNF 蛋白表达中起作用，从而影响精神分裂症的认知障碍，这表明开发针对精神分裂症的认知增强治疗可能需要考虑基于 micro-RNA 的策略。
