2022, Vol. 26 ›› Issue (23): 3676-3682

Metabotropic glutamate receptor improves post-stroke cognitive impairment in enriched environments

Liu Jiayu1, Yan Ping1, Zhang Yu1, Zhou Hongyu2, Wang Xin2   

Abstract: BACKGROUND: Enriched environment intervention can improve cognitive impairment to a certain extent. Glutamate is an excitatory amino acid closely related to cognition. The effect and mechanism of enriched environment on glutamate receptor in post-stroke mice are still unclear.  
OBJECTIVE: To investigate the effect of metabotropic glutamate receptor on improving post-stroke cognitive impairment and its mechanism in enriched environments.
METHODS: The mouse model of stroke was made by light embolus method, and the mice with cognitive impairment were selected through Y maze test in comparison with the sham operation group. The mice were randomly divided into three groups: sham operation+standard environment operation group (Sham+SE), post-stroke cognitive impairment+standard environment (PSCI+SE) group and post-stroke cognitive impairment+enriched environment (PSCI+EE) group. After 14 days in the corresponding environment, Y maze was used to detect the cognitive function of the frontal lobe. New object recognition experiment was used to detect the learning and memory ability of the hippocampus. Quantitative real-time PCR was used to detect the mRNA transcription level of metabotropic glutamate receptor in the frontal lobe and hippocampus, and western blot was used to detect the protein expression of metabotropic glutamate receptor, acetylated histone H3, CAMP response binding protein in the frontal lobe and hippocampus.  
RESULTS AND CONCLUSION: Compared with the Sham+SE group, the Y maze spontaneous alternation rate was significantly decreased (P < 0.001), the new object exploration rate was significantly decreased (P < 0.001), metabotropic glutamate receptor mRNA levels in the frontal lobe and hippocampus were downregulated (P < 0.01), and the expression of related proteins in the frontal lobe and hippocampus was significantly decreased in the PSCI+SE group (P < 0.01). The spontaneous alternation rate, new object exploration rate, and metabolic glutamate receptor mRNA in the frontal lobe and hippocampus were significantly decreased, and mRNA transcription, frontal lobe and hippocampus related protein expression were significantly improved in the PSCI+EE group compared with the PSCI+SE group (P < 0.05), but there was still a significant difference between PSCI+EE group and Sham+SE group (P < 0.05). To conclude, enriched environment intervention is helpful to improve the memory of mice after stroke, and its mechanism may be through increasing the phosphorylation of CAMP response binding protein, acetylation homeostasis imbalance, increasing metabotropic glutamate receptor 2 mRNA transcription and protein expression, and ultimately improving cognitive function.
Key words: stroke, cognitive impairment, enriched environment, standard environment, glutamate, metabotropic glutamate receptor