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Effects of intrahippocampal NAC(61-95) injections on memory in the rat and attenuation with vitamin E

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Kim, Eun-Mee, Elliot, J. J., Hobson, P. and O'Hare, E. (2009) Effects of intrahippocampal NAC(61-95) injections on memory in the rat and attenuation with vitamin E. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 33 (6). pp. 945-951. [Journal article]

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DOI: 10.1016/j.pnpbp.2009.04.020

Abstract

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 alpha-synuclein protein is the major component of LB's and the non-amyloid component (NAC) region of alpha-synuclein, residues 61-95, is essential for the aggregation and toxicity of this protein. The current study evaluated the effect of pre-aggregated NAC(61-95) 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 NAC(61-95) (5 mu l suspension), and two groups were injected bilaterally into the dorsal hippocampus with sterile water (5 mu l). Subgroups were treated with either vitamin E (150 mg/kg in Soya oil) or vehicle (Soya oil) daily. Injection of NAC(61-95) induced memory deficits and vitamin E treatment alleviated these. In addition, NAC(61-95) injections induced activated astrocytes and chronic treatment with vitamin E reduced the numbers of activated astrocytes. These results suggest that aggregated NAC(61-95) and associated oxidative stress, may play a role in the pathogenesis of cognitive deficits seen in PD-induced dementia. (C) 2009 Elsevier Inc. All rights reserved.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Psychology
Research Institutes and Groups:Psychology Research Institute
Psychology Research Institute > Behavioural Neuroscience & Behavioural Analysis
ID Code:1627
Deposited By:Mrs Fiona Harkin
Deposited On:23 Dec 2009 09:27
Last Modified:13 Mar 2012 16:34

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