Research ReportThe effects of bilateral common carotid artery occlusion on expression of peripherin and choline acetyltransferase activity in C57BL/6 mice

Peripherin is a 57-kDa type III neuronal intermediate filament protein that appears to play a role in neurite elongation during development and axonal regeneration. Its role in the pathogenesis of cognitive deficits caused by cerebral ischemia is unknown. The purpose of this study was to investigate the location and level of peripherin expression in the central nervous system in response to transient global cerebral ischemia, and the resultant effect of peripherin expression on the cholinergic neurons and Choline acetyltransferase (ChAT) activity in this mouse model of ischemia. Transient global cerebral ischemia was induced in C57BL/6 mice by 20-min bilateral common carotid artery occlusion (BCCAO) with microclips. The resulting impairment of spatial learning and memory was investigated by Morris water maze testing. Peripherin expression was evaluated by immunostaining and Western Blot assay of brain sections. Peripherin expression increased in neurons of the cortex, hippocampus, and thalamus after BCCAO. By double immunofluorescence staining, neurons showed a cytoplasmic co-localization of peripherin and MAP-2, but not of peripherin and GFAP. ChAT activity was determined spectrophotometrically using the assay kit. There was significantly decreased ChAT activity in the cerebral cortex, hippocampus and thalamus in mice of the BCCAO group (p<0.05), compared with the sham group. After BCCAO, peripherin overexpression was significantly correlated with reduction in ChAT activity (r=−0.929; p<0.01), spatial learning and memory were impaired, and peripherin expression was induced in neurons but not astrocytes. Thus, peripherin appears to be a participant in learning and memory impairment in mice.

► BCCAO impaired spatial learning and memory in mice. ► ChAT activity was reduced in BCCAO mice. ► Peripherin expression increased in neurons of cortex, hippocampus and thalamus. ► Neurons showed a cytoplasmic co-localization of peripherin and MAP-2. ► Neuronal peripherin overexpression was inversely related to ChAT activity.