The effect of optical atrophy-1 on hippocampal neuronal apoptosis and mitochondrial function in depressed mice
Objective To investigate the effects of optic atrophy protein-1(OPA1)overexpression on hippocampal neuron apoptosis and mitochondrial function in depressed mice.Methods Thirty-two C57BL/6J mice were randomly divided into control group(CON group),chronic stress group(CMS group),chronic stress+empty vector group(CMS+NC group),chronic stress+OPA1 overex-pressed vector group(CMS+OPA1 OE group).The depression model was established by chronic stress,the stress lasted for 3 weeks,and then control virus and OPA1 lentvirus overexpression were injected into the lateral ventricles of mice in CMS+NC group and CMS+OPA1 OE group,respectively.Before and 1 week after injection,depression-like behavior was evaluated by sugar water prefer-ence test and tail suspension test,and molecular biological detection was performed after behavioral test.Results After lentvirus inter-vention,the percentage of sugar and water preference in CMS+OPA1 OE group was higher than that in CMS and CMS+NC groups,and the tail suspension time in CMS+OPA1 OE group was lower than that in CMS and CMS+NC groups,with statistical significance(P<0.05).The apoptosis rate of hippocampal neurons and the expression rate of Caspase-3 positive cells in CMS group and CMS+NC group were higher than those in CON group,and the apoptosis rate of hippocampal neurons and the expression rate of Caspase-3 positive cells in CMS+OPA1 OE group were lower than those in CMS group and CMS+NC group,with statistical significance(P<0.05).The expression levels of mitochondrial fusion proteins MFN1 and MFN2 in hippocampus of mice in CMS group and CMS+NC group were lower than those in CON group,and the expression levels of MFN1 and MFN2 in hippocampus of mice in CMS+OPA1 OE group were higher than those in CMS group and CMS+NC group,with statistical significance(P<0.05).The adenosine triphosphate(ATP)level of mice in the hippocampus of CMS group and CMS+NC group was lower than that of CON group,and the ATP level of CMS+OPA1 OE group was higher than that of CMS group and CMS+NC group,with statistical significance(P<0.05).Conclusion OPA1 expression levels in the hippocampus of depressed mice decreased,and overexpression of OPA1 can improve depression-like behavior,hippocampal neuron apoptosis and mitochondrial function of mice.OPA1 may be a biological marker of depression and a po-tential therapeutic target.
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