Light treatment ameliorates sub-chronic MK-801-induced cognitive deficits in mice through up-regulating BDNF/p-CREB/p-ERK signaling pathway

Abstract

Abstract Cognitive impairment associated with schizophrenia (CIAS) is regarded as a core symptom of the illness, and there is still no effective treatment. Light plays an important role in regulation of cognitive functions. However, whether light treatment (LT) can improve CIAS remains unknown. The current study investigated the efficacy of LT on CIAS and explored the underlying molecular mechanisms in a CIAS model. The CIAS and control group were sub-chronically injected with MK-801 and saline respectively, and the LT/CIAS group were CIAS mice exposed to LT (3,000 Lux, 2 hr/day, 3 weeks). Results showed that the performance of LT/CIAS mice significantly improved in the novel object recognition test, novel location recognition test and Morris water maze compared with the CIAS group. And the behavioral improvement effects of LT could last over 4 weeks after LT was terminated. Golgi-cox staining revealed that the dendritic spine density and morphological complexity of hippocampal CA1 pyramidal neurons were increased after 3 weeks LT. Further research found that higher expression of brain-derived neurotrophic factor (BDNF), accompanied by elevated cAMP response element-binding phosphorylation (p-CREB) level in the hippocampus of LT/CIAS group compared to the CIAS group. Moreover, LT elevated phosphorylated extracellular signal-regulated kinase (p-ERK) level in the hippocampus of LT/CIAS group compared to the CIAS group. Taken together, long term LT ameliorated sub-chronic MK-801-induced cognitive deficits in mice, and the altered dendritic spines density and morphology of CA1 pyramidal neurons were rescued in LT/CIAS mice group, which might associate with up-regulating BDNF/p-CREB/p-ERK signaling pathway in LT/CIAS mice.