Influence of enriched environment on visual function and synaptic plasticity in adult amblyopic mice

Abstract

Objective To examine role and possible mechanism of enriched environment (EE) on regulating recovery of visual function in adult monocular deprivation amblyopia mice. Methods A total of 72 healthy Kunming mice were divided into normal control group, monocular deprivation (MD) group, MD+ EE group and MD+ fluoxetine group by random number table.Except for the normal control group, the mice in the other groups were sutured on the right eyelid 21 days after birth to establish MD amblyopia model.the mice were fed in standard environment or EE for 4 weeks according to the group.Visual acuity and flash visual evoked potential (F-VEP) of mice in each group were detected.The distribution of microtubule associated protein 2 (MAP2) in visual cortex of adult amblyopic mice were detected by immunohistochemistry.The expression of MAP2, synaptophysin (SYP) and postsynaptic density protein-95 (PSD-95) protein in visual cortex of adult amblyopic mice were detected by western blot.The experimental protocol was approved by the Animal Care and Use Committee of Hunan Children's Hospital and conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Results There was a significant difference in the visual acuity of deprived eye among each group (F=114.632, P<0.001). The visual acuity in MD group is lower than that in normal control group, with a significant difference (t=15.480, P<0.001). Compared with MD group, visual acuity was restored in MD+ EE group and MD+ fluoxetine group, with significant differences (t=15.071, P<0.001; t=14.841, P<0.001). There was a significant difference in the P2 latency and amplitude of F-VEP in deprived eye among each group (F=36.510, P=0.000; F=34.140, P=0.000). Compare with normal control group, P2 latency was prolonged and P2 amplitude of F-VEP was decreased in deprived eye in MD group, with significant differences (t=10.220, P=0.000; t=10.09, P=0.000). Western blot assay showed that there was a significant difference in the expression of MAP2 in visual cortex contralateral deprived eye among each group (F=18.142, P=0.000). The expression of MAP2 in MD group was significantly lower than that in normal contral group (t=3.056, P<0.01); Compared with MD group, MAP2 expression was increased in MD+ EE group and MD+ fluoxetine group (t=2.541, P=0.031; t=2.157, P=0.017). There were significant differences in the expression of SYP and PSD-95 in visual cortex contralateral to deprived eye among each group (F=12.871, P=0.000; F=25.060, P=0.000). Compared with normal contral group, SYP and PSD-95 expression in visual cortex were down-regulated in MD group, with significant differences (t=6.054, P=0.000; t=8.631, P=0.000). The expression of SYP and PSD-95 protein in MD+ EE group and MD+ fluoxetine group were significantly higher than those in MD group (all at P<0.05). Conclusions EE can recover visual function through up-regulating the expression of MAP2, which can modulate the dendritic branch trim and neural plasticity of visual cortex in adult MD mice. Key words: Enriched environment; Monocular deprivation; Amblyopia; Visual cortex; Plasticity