Effects of intrahippocampal NAC 61-95 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 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 microl suspension), and two groups were injected bilaterally into the dorsal hippocampus with sterile water (5 microl). 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.
School of Psychology, University of Ulster at Coleraine, Co. Londonderry, Northern Ireland, BT52 1SA, United Kingdom. e.kim@ulster.ac.uk
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O'Hare
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology / Q000627:therapeutic use*; D051844:alpha-Synuclein / Q000008:administration & dosage / Q000633:toxicity*
D010446:Peptide Fragments; D051844:alpha-Synuclein; C404769:alpha-synuclein (61-95); D014810:Vitamin E