Effects of intrahippocampal NAC61-95 injections on memory in the rat and attenuation with vitamin E

Parkinson's disease (PD)-related dementia affects approximately 40% of PD patients and the severity of this dementia correlates significantly with the density of Lewy body (LB) deposition in the PD brain. Aggregated α-synuclein protein is the major component of LB's and the non-amyloid component (NAC) region of α-synuclein, residues 61-95, is essential for the aggregation and toxicity of this protein. The current study evaluated the effect of pre-aggregated NAC61-95 injected into the CA3 area of the dorsal hippocampus of the brain on memory in the rat. Previous research has suggested that oxidative stress processes may play a role in the neuropathology of PD, therefore the effect of treatment with vitamin E, an antioxidant, was also evaluated. Male Sprague-Dawley rats were trained in two-lever operant chambers under an alternating-lever cyclic-ratio (ALCR) schedule of food reinforcement. When responding showed no trends, subjects were divided into four groups. Two groups were injected bilaterally into the dorsal hippocampus with aggregated NAC61-95 (5 μl suspension), and two groups were injected bilaterally into the dorsal hippocampus with sterile water (5 μl). Subgroups were treated with either vitamin E (150 mg/kg in Soya oil) or vehicle (Soya oil) daily. Injection of NAC61-95 induced memory deficits and vitamin E treatment alleviated these. In addition, NAC61-95 injections induced activated astrocytes and chronic treatment with vitamin E reduced the numbers of activated astrocytes. These results suggest that aggregated NAC61-95 and associated oxidative stress, may play a role in the pathogenesis of cognitive deficits seen in PD-induced dementia.