Neuroprotective Potential of Safinamide Mesylate in Streptozotocin Induced Sporadic Alzheimer's Disease in Rats

Abstract

Alzheimer’s disease (AD) is a complex, slowly progressive neurodegenerative disorder marked by loss of memory, mood changes, and cognitive impairment. The two pathological hallmarks of AD are the deposition of extracellular Aβ plaques and intraneuronal neurofibrillary tangles. Other pathological mechanisms involved in the progression of AD are insulin desensitization, lipid metabolism abnormalities, synapse dysfunction, oxidative stress, excitotoxicity, neurotransmitter deficits, neuroinflammation, etc. The present study was designed to investigate the neuroprotective potential of Safinamide mesylate in Streptozotocin induced sporadic Alzheimer’s disease in rats. STZ (3mg/kg) was administered bilaterally through the intracerebroventricular (i.c.v.) route on the 1st and 3rd days in rats. Safinamide a potent MAO-B inhibitor and a neuroprotective drug was administered at dose levels of 15 and 30 mg/kg/i.p. for treating AD from day 15th to 28th. Open field test, novel object recognition test, and Morris water maze behavioral parameters were done to access the learning memory, spatial memory, recognition memory, and motor coordination in rats. The cognitive and memory deficits by the significant increase in oxidative stress markers produced by i.c.v. STZ was determined by biochemical analysis. The neurodegeneration in the hippocampus and cortex region was observed through histopathological analysis. Safinamide treatment significantly attenuated the STZ induced memory decline, neuroinflammation and prevented the neuronal loss. The observed cognitive improvement followed by safinamide administration may be due to its neuroprotective, anti-inflammatory, and anti-apoptotic activity. The observed outcomes of the present study suggest the neuroprotective potential of safinamide in cognitive disorders and memory dysfunction.