Cui Keke, Zhou Yiying, Zhang Lizhi, Ying Yudong, Xue Yan, Zhang Xiaoqin, Wang Qinwen, Shen Haowei, Zhou Wenhua, Gao Feng, Wang Zhengchun
Zhejiang Key Laboratory of Pathophysiology, Basic Medical Sciences, Health Science Center, Ningbo University, 818 Fenghua Rd, Ningbo, 315211, Zhejiang, China.
Key Laboratory of Addiction Research of Zhejiang Province, Kang Ning Hospital, Ningbo, 315010, China.
Mol Neurobiol. 2025 May;62(5):5947-5960. doi: 10.1007/s12035-024-04653-z. Epub 2024 Dec 14.
Cognitive impairment associated with schizophrenia (CIAS) is considered a core symptom of the illness, yet effective treatments remain limited. Light plays an important role in regulating cognitive functions. However, the potential of light treatment (LT) to improve CIAS remains unknown. The current study aimed to investigate the efficacy of LT on CIAS and explore the underlying molecular mechanisms in a CIAS animal model. The CIAS group and the control group were sub-chronically administered MK-801 and saline, respectively. Concurrently, the LT/CIAS group, consisting of CIAS mice, received LT exposure (3000 Lux, 2 h/day, for 3 weeks). Results showed a significant enhancement in cognitive performance among LT/CIAS mice, as evidenced by improvements in the novel object recognition (NOR) test, novel location recognition (NLR) test, and Morris water maze (MWM) compared to the CIAS group. Remarkably, these beneficial effects of LT persisted for over 4 weeks after the termination of LT. Furthermore, Golgi-cox staining unveiled an increased dendritic spine density and enhanced morphological complexity in hippocampal CA1 pyramidal neurons following 3 weeks of LT. Subsequent investigations revealed elevated levels of brain-derived neurotrophic factor (BDNF) and heightened phosphorylation of cAMP response element-binding phosphorylation protein (p-CREB) in the hippocampus of the LT/CIAS group compared to the CIAS group. Moreover, LT elevated the phosphorylated extracellular signal-regulated kinase (p-ERK) in the hippocampus of the LT/CIAS group relative to the CIAS group. In conclusion, the current study demonstrates that long-term LT effectively ameliorated sub-chronic MK-801-induced cognitive deficits in mice, and the altered dendritic spine density and morphology of CA1 pyramidal neurons were rescued in the LT/CIAS group, potentially through the up-regulation of the BDNF/p-CREB/p-ERK signaling pathway in LT/CIAS mice.
与精神分裂症相关的认知障碍（CIAS）被认为是该疾病的核心症状，但有效的治疗方法仍然有限。光线在调节认知功能方面起着重要作用。然而，光疗法（LT）改善CIAS的潜力尚不清楚。当前的研究旨在调查LT对CIAS的疗效，并在CIAS动物模型中探索其潜在的分子机制。CIAS组和对照组分别亚慢性给予MK-801和生理盐水。同时，由CIAS小鼠组成的LT/CIAS组接受LT照射（3000勒克斯，每天2小时，持续3周）。结果显示，与CIAS组相比，LT/CIAS小鼠的认知能力有显著提高，新物体识别（NOR）测试、新位置识别（NLR）测试和莫里斯水迷宫（MWM）的结果均有所改善。值得注意的是，LT的这些有益效果在LT终止后持续了4周以上。此外，高尔基-考克斯染色显示，LT照射3周后，海马CA1锥体神经元的树突棘密度增加，形态复杂性增强。随后的研究表明，与CIAS组相比，LT/CIAS组海马中脑源性神经营养因子（BDNF）水平升高，cAMP反应元件结合磷酸化蛋白（p-CREB）的磷酸化增强。此外，与CIAS组相比，LT使LT/CIAS组海马中的磷酸化细胞外信号调节激酶（p-ERK）升高。总之，当前的研究表明，长期LT有效地改善了亚慢性MK-801诱导的小鼠认知缺陷，并且LT/CIAS组CA1锥体神经元的树突棘密度和形态改变得到了恢复，这可能是通过上调LT/CIAS小鼠中的BDNF/p-CREB/p-ERK信号通路实现的。
