Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; Yunnan Clinical Research Center for Mental Health, Kunming, Yunnan, China.
Neurosci Lett. 2023 Aug 24;812:137410. doi: 10.1016/j.neulet.2023.137410. Epub 2023 Jul 24.
The pathogenesis and treatment of cognitive dysfunction in patients with schizophrenia (SCZ) remains a challenge. Exploring new effective treatment strategies is relevant for the improvement of cognitive function. Aripiprazole (ARI) is an atypical antipsychotic that improves some cognitive functions. Nerve growth factor (NGF) has been shown to improve cognitive function in certain neurological impairments and partial neurological deficits, but its mechanism of action in cognitive dysfunction in SCZ is unclear. In this study, we established schizophrenia mouse model with dizocilpine (MK-801); treated mice with ARI alone or in combination with NGF; assessed spontaneous activity and cognitive function using open field test and Morris water maze test; and measured brain-derived neurotrophic factor (BDNF) protein and mRNA expression levels using immunohistochemistry and molecular biology assays. The results showed that ARI alone or in combination with NGF can improve increased spontaneous activity and spatial learning memory deficits in model mice by elevating BDNF expression levels in prefrontal cortex (PFC) and hippocampus (HIP). The results suggest that ARI combined with NGF can improve cognitive function in SCZ, which provides new ideas and directions for the clinical treatment of cognitive dysfunction in SCZ.
精神分裂症(SCZ)患者认知功能障碍的发病机制和治疗仍然是一个挑战。探索新的有效治疗策略对于改善认知功能至关重要。阿立哌唑(ARI)是一种新型抗精神病药,可改善某些认知功能。神经生长因子(NGF)已被证明可改善某些神经损伤和部分神经缺陷的认知功能,但在 SCZ 认知功能障碍中的作用机制尚不清楚。在这项研究中,我们使用地佐环平(MK-801)建立了精神分裂症小鼠模型;用阿立哌唑(ARI)单独或联合 NGF 治疗小鼠;使用旷场试验和 Morris 水迷宫试验评估自发活动和认知功能;并使用免疫组织化学和分子生物学检测前额叶皮层(PFC)和海马(HIP)中脑源性神经营养因子(BDNF)蛋白和 mRNA 表达水平。结果表明,ARI 单独或联合 NGF 可通过提高前额叶皮层(PFC)和海马(HIP)中 BDNF 的表达水平,改善模型小鼠自发活动增加和空间学习记忆缺陷。结果提示,ARI 联合 NGF 可改善 SCZ 的认知功能,为 SCZ 认知功能障碍的临床治疗提供了新思路和方向。