Mechanism of photosensitive STIM1 calcium channel driven retinal injury stress depression

Abstract

Objective To investigate the occurrence of stress depression caused by retinal cells death driven by activation of photosensitive STIM1 calcium channel and the changes in brain inflammation related to the visually-associated brain regions. Methods A mouse model of retinal injury driven by light was constructed by injecting STIM1 virus into the vitreous body of mouse eyeball. HE staining and depression-related behavior test were performed to assess the severity of retinopathy and incidence of depression. Reverse transcription-PCR (RT-PCR), Western blotting and immunofluorescence assay were used to analyze the changes of microglial cells, inflammatory factors (IL-6 and MIP-1α), nerve cell damage marker (S100B), apoptotic protein (Caspase-3) and myelin basic protein (MBP) in the depressive mice. Results ① The cell density in each layer of the mouse retina were decreased significantly under the light mode of 3 h/d for 7 consecutive days (P < 0.05). ② In the open field test, the times of entering the central area, moving distance in the central area and total distance of movement were obviously decreased (P < 0.05), the index of sucrose preference of the sucrose preference test was significantly decreased (P < 0.01), and the immobile time in the forced swimming test and the tail suspension test was notably increased (P < 0.001) in the mice from the photosensitive group. The positive rate of depression in all the 4 tests (open field test, sucrose preference test, forced swimming test and tail suspension test) was 23.26%. ③The density of IBa-1+ cells in the visual cortex and dorsolateral geniculate nucleus was elevated in the depressive mice of the photosensitive group (P < 0.05). The expression of IL-6 and MIP-1α at mRNA level was obviously elevated (P < 0.000 1), as well as the expression of S100B and Caspase-3 at protein level was significantly enhanced (P < 0.001), while the MBP protein in the white matter was clearly weakened (P < 0.05). The intensity of MBP fluorescence signal was evidently reduced in the corpus callosum (cc) area and cingulate gyrus (cg) area in white matter (P < 0.000 1). Conclusion A stress depression-like mouse model caused by light-driven retinal injury is successfully constructed. Pathogenesis of depression is closely associated with inflammatory environment and neuronal apoptosis in the vision-related brain regions and demyelinating injury in white matter.

Keywords

• retinal damage
• stress depression
• photosensitive modification stim 1
• behavioristics
• demyelination