Selegiline Improves Cognitive Impairment in the Rat Model of Alzheimer's Disease

Alzheimer's disease (AD) is a progressive neurological disorder characterized by cognitive decline. This study was undertaken to evaluate the effects of selegiline (SEL) against AD-induced cognitive deficits and explore the possible involved mechanisms. AD was induced by unilateral intracerebroventricular (U-ICV) injection of 5 mu g of amyloid beta1-42 (A beta 1-42), and oral administration of SEL (0.5 mg/kg/day) was performed for 30 consecutive days. A beta injection resulted in spatial cognitive decline, as demonstrated by a decrease in the time spent in the target zone on the probe day (P < 0.01) in the Barnes maze test (BMT). This spatial cognitive decline was associated with disrupted synaptic plasticity, as indicated by reductions in both components of hippocampal long-term potentiation (LTP), namely population spike amplitude (P < 0.001) and field excitatory postsynaptic potential (P < 0.001). On the other hand, the injection of A beta resulted in oxidative stress by decreasing total thiol group (TTG) content and increasing malondialdehyde (MDA) levels in the rat plasma (P < 0.001). Additionally, the number of healthy cells in the hippocampal dentate gyrus (DG) and CA1 regions was reduced in AD rats (P < 0.001). However, oral administration of SEL improved spatial cognitive decline in the A beta-induced AD rats. The results suggest that improvement of neuroplasticity deficiency, regulation of oxidant/antioxidant status, and suppression of neuronal loss by SEL may be the mechanisms underlying its beneficial effect against AD-related spatial cognitive impairment.