Diosmin is neuroprotective in a rat model of scopolamine-induced cognitive impairment

Abstract

Objective: Scopolamine, a muscarinic cholinergic receptor antagonist, is used as a standard pharmaceutical model for inducing cognitive impairment in animals. Several cognitive behaviors, such as motor function, anxiety, short-term memory, attention are affected by injections of scopolamine. In this study, we have assessed the effects of administration of the diosmin (DM, 50 and 100 mg/kg), before injection of 0.4 mg/kg of scopolamine on memory and motor function, the hippocampal dentate gyrus (DG) electrophysiological activity as well as brain inflammation.

Methods: Eighty male rats were randomly divided into five groups (Control, Veh + scopolamine, DM (50) + scopolamine and DM (100) + scopolamine, donepezil (DP) + scopolamine, n = 16). Scopolamine (0.4 mg/kg, i.p.) is used, in order to induce an animal model of cognitive impairment. Rats pretreated with doses of 50 and 100 mg/kg of DM, 3 mg/kg of DP and/or normal saline for 7 days, before injection of scopolamine. Long-term potentiation (LTP) recording was done for electrophysiological activity assessment. Passive avoidance task (PAT), rotarod and spatial memory tests were evaluated, using a shuttle box, rotarod apparatus and Morris water maze (MWM), respectively.

Results: Results indicated that DM at doses of 50 and 100 mg/kg, significantly reversed the LTP (amplitude and slope) impairment of the hippocampal DG neurons, induced by scopolamine. Also, DM at doses of 50 and 100 mg/kg increased the percent of the total time that animals spent in goal quarter, the step-through latency (s) and bar latency time in an animal model of cognitive impairment (p < 0.01 and p < 0.001), respectively. The concentrations of TNF-α in hippocampus of the DM and donepezil groups was significantly lower than the Veh + scopolamine group (p < 0.01).

Conclusion: This study revealed that the DM is effective in preventing the disruption of synaptic plasticity and cognitive impairments, induced by scopolamine. The positive effects of DM may be mediated through a decline in the TNF- α concentrations in hippocampus as a pro-inflammatory cytokine. Thus, the acquired results suggested that the DM can be used, as a useful and suitable agent for memory restoration, in the treatment of dementia, seen in elderlies.

Keywords: Cognitive deficits; Diosmin; Long-term potentiation; Scopolamine.