Reactivation of visual cortical plasticity by caloric restriction mediated by AMPK-SIRT1 pathway from monocular deprivation in adult mice

Objective

This study was to investigate the effect of caloric restriction on the plasticity of visual cortex in adult monocular deprivation (MD) amblyopic mice, as well as to promote the treatment of amblyopia, and to explore the possible molecular mechanism of this benefical effect.

Methods

Fifty healthy newborn Kunming mice of clean grade were randomly divided into 3 groups using a random number table method: normal control group (n=14), MD+ ad libitum group (n=18) and MD+ caloric restriction group (n=18). A mouse model of adult MD amblyopia was established, and caloric restriction intervention and ad libitum were performed on MD+ caloric restriction group and MD+ ad libitum group, respectively.The visual acuity and flash visual evoked potential (F-VEP) of each group were detected.The synaptic structure of visual cortex neurons was observed by transmission electron microscope, and the expression of phosphorylated AMP-activated protein kinase-α (p-AMPKα) and silent information regulator 1 (SIRT1) in visual cortex were detected by Western blot.The animal feeding and use was in accordance with the standards set by the ARVO.

Results

The weight of mice in MD+ caloric restriction group increased from the beginning of the first week, and was significantly lower than that in the MD+ ad libitum group (P<0.05). Compared with the MD+ ad libitum group, the visual acuity was restored, the latency was shortened, and the amplitude of F-VEP was increased in the deprived eyes of MD+ caloric restriction group (all at P<0.05). Transmission electron microscope observation showed that the width of synaptic gap of visual cortical neurons was significantly narrower, and the thickness of postsynaptic density was significantly thicker in MD+ caloric restriction group than that in the MD+ ad libitum group (both at P<0.05); compared with the normal control group, the synaptic gap was widened and the postsynaptic density was significantly thicker than that in the MD+ ad libitum group (both at P<0.05). Western blot showed that the expression of p-AMPKα in visual cortex in the normal control group, MD+ caloric restriction group and MD+ ad libitum group was 0.89±0.03, 0.94±0.02 and 0.74±0.02, and the expression of SIRT1 was 0.97±0.11, 0.95±0.14 and 0.58±0.13, respectively, showing significant differences among the three groups (F=14.57, P=0.00; F=23.91, P=0.00), the expressions of p-AMPKα and SIRT1 in visual cortex were increased in MD+ caloric restriction group than those in MD+ ad libitum group (both at P<0.05).

Conclusions

Caloric restriction can restore the ultrastructure of synapses and improve the visual cortical plasticity in adult MD mice, so that help to improve visual function.Its mechanism may be related to the activation of AMPK-SIRT1 pathway.