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. 2025 May;62(5):5947-5960.
doi: 10.1007/s12035-024-04653-z. Epub 2024 Dec 14.

Light Treatment Ameliorates Sub-chronic MK-801-Induced Cognitive Deficits in Mice Through Up-regulating BDNF/p-CREB/p-ERK Signaling Pathway

Keke Cui #  1 , Yiying Zhou #  2 , Lizhi Zhang  1 , Yudong Ying  1 , Yan Xue  1 , Xiaoqin Zhang  2   1 , Qinwen Wang  1 , Haowei Shen  2   1 , Wenhua Zhou  2 , Feng Gao  3 , Zhengchun Wang  4   5   6
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Light Treatment Ameliorates Sub-chronic MK-801-Induced Cognitive Deficits in Mice Through Up-regulating BDNF/p-CREB/p-ERK Signaling Pathway

Keke Cui et al. Mol Neurobiol. 2025 May.

Abstract

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.

Keywords: BDNF/p-CREB/p-ERK; Cognition impairments; Dendritic spines; Light treatment; MK-801.

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Conflict of interest statement

Declarations. Ethics Approval: All experiments were conducted in line with the National Institutes of Health Guide for the Care and Use of Laboratory Animal, which were approved by the Animal Care and Use Committees of Ningbo University. Consent to Participate: Not applicable. Consent for Publication: All authors read and approved the final manuscript. Conflict of Interest: The authors declare no competing interests.

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