title: A study of glutamate levels, NR1, NR2A, NR2B receptors and oxidative stress in rat model of Japanese encephalitis.
abstract: There is paucity of studies on the role of glutamate excitotoxicity in cell damage in Japanese encephalitis. In this study the glutamate levels and its NMDA receptors, and oxidative stress markers in different brain regions have been evaluated and correlated with neurobehavioral changes at different time points. Twelve day old Wistar rats were inoculated with 3×106pfu/ml intracerebrally. The neurobehavioral effects were evaluated by spontaneous locomotor activity (SLA), grip strength and rota rod test on 10, 33 and 48days post inoculation (dpi). Glutamate level was evaluated by enzyme linked immunosorbent assay, mRNA gene expression of ionotropic glutamate receptors N-methyl d-aspartate (NMDA) receptor 1, 2A and 2B (NR1, NR2A and NR2B) were evaluated by real time PCR. Malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GPx) levels were measured by spectrophotometer in different brain regions of JEV infected rats on 10, 33 and 48dpi. There was significant increase in motor deficit, grip strength and decreased locomotor activity on 10 and 33dpi. Glutamate levels were increased in thalamus, midbrain, frontal cortex, striatum and cerebellum on 10 and 33dpi and were followed by a recovery on 48dpi. Glutamate NMDR receptors NR1, NR2A and NR2B were reduced in thalamus, midbrain, frontal cortex, striatum and cerebellum on 10dpi which was followed by recovery after 33dpi. A significant increase in MDA level in thalamus, midbrain, frontal cortex, striatum and cerebellum was noted on 10 and 33dpi. The antioxidant GSH and GPx were significantly reduced in these brain regions on 10 and 33dpi. Glutamate, MDA, GSH and GPx correlated in different brain regions as the disease progress. Increased Glutamate level may be related to oxidative stress and may be responsible for behavioral alterations in rat model of Japanese encephalitis.
authors.affiliation: Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Science, Raebareily Road, Lucknow, India.
authors.forename: Prashant Singh
authors.initials: PS
authors.lastname: Chauhan
authors.affiliation: Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Science, Raebareily Road, Lucknow, India. Electronic address: drukmisra@rediffmail.com.
authors.forename: Usha Kant
authors.initials: UK
authors.lastname: Misra
authors.affiliation: Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Science, Raebareily Road, Lucknow, India.
authors.forename: Jayantee
authors.initials: J
authors.lastname: Kalita
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000472:pathogenicity; D004672:Encephalitis, Japanese / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015967:Gene Expression Regulation, Viral; D018698:Glutamic Acid / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008124:Locomotion; D001523:Mental Disorders / Q000209:etiology / Q000821:virology; D053580:Muscle Strength / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005979:Glutathione Peroxidase; D005978:Glutathione
keywords: Behavioral impairment; Glutamate; Glutathione; Japanese encephalitis; Malondialdehyde; N-Methyl d-aspartate receptors