Neuroprotective effect of genistein on cognitive impairment in vascular dementia experimental mice model

Abstract

The present study aims to determine the neuroprotective efficacy of genistein on vascular dementia in experimental model mice and explore the underlying mechanisms. To induce vascular dementia, chronic bilateral common carotid artery occlusion was performed on female mice brain by occluding both common carotid arteries for 30 min followed by 24 h reperfusion to induce neuronal injury. After surgery, the mice were treated daily by oral administration of genistein (5.0, and 10.0 mg/kg, i.p., o.d.) for one months. The cognition function of treated mice, were evaluated by Morris Water Maze (MWM) test, neurological functions measured as short-term memory and motor performance. In addition, cerebral infarct size, oxidative damage, mitochondrial activity in terms of neuronal apoptosis and cellular viability, Nissl and TUNEL staining were chosen to assess neuronal damage within the hippocampal CA1 area. In present study, there was an increase in cognitive impairment and neuronal damages within CA1 hippocampal subregion caused by chronic cerebral hypoperfusion. Genistein administration significantly counteracted cognitive impairment and re-established motor performance in vascular dementia in mice. Genistein was able to prevent cognitive deficits, and reversed CCH-induced hippocampal neuronal loss and apoptosis. Genistein treatment significantly reduced neuronal apoptosis and increased cellular viability, almost completely suppressed the circulating dipeptidyl peptidase-4 activity, and enhanced glucagon-like peptide-1 concentration in vascular dementia in experimental model mice. This study suggests that genistein has potent neuroprotective activity against chronic cerebral hypoperfusion and may be considered as a potential treatment for cognitive deficits and neuronal injury in the hippocampal CA1 area.