3-Nitropropionic acid-induced neurotoxicity as an experimental model of Huntington's disease: Possible behavioral, biochemical and cellular alterations

Huntington's disease (HD) is a neurodegenerative disorder, characterized by behavioral and psychiatric problems. Investigations into the mechanisms of neuronal death in HD have been revolved so far around excitatory amino acids as the primary cause of neuronal loss. A number of recent reports suggest that oxidative stress play a key role in the pathogenesis of HD. Presently, there is no adequate drug treatment available for the effective management of HD. For the better understanding of this disease, animal models are the best tools to study disease pathogenesis. 3-Nitropropionic acid (3-NP) is a mitochondrial toxin, which causes selective neuronal destruction in the basal ganglia and it inhibits succinate dehydrogenase, a key enzyme of respiratory chain that blocks mitochondrial complex-II in the Krebs's cycle, and deplete ATP levels. Based on above, present work highlights the role of oxidative stress in an experimental model of HD with the help of behavioral and biochemical alterations in animals. 3-NP (10 mg/kg, i.p.) was administered for 14 day and behavioral observations (motor and cognitive) were done on 1 st , 5 th 10 th and 15 th day after 3-NP. Various biochemical parameters (malondialdehyde, nitrite concentration as well as superoxide and catalase enzyme levels) were estimated on in striatum and cortex. Systemic 3-NP (10 mg/kg) administration for 14 days significantly reduced locomotor activity, body weight, grip strength and oxidative defense (malondialdehyde, nitrite concentration as well as superoxide and catalase enzyme levels) in the striatum and cortex. Based on above, present work discusses animal model of 3-NP-induced neurotoxicity and associated behavioral and biochemical changes in animals.