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Indian Journal of Pharmaceutical Education and ResearchNOW IN
Article

Ameliorative Effects of 3-methyladenine and Chloroquine in 3-nitropropionic-induced Huntington’s Disease like Symptoms in Mice

Jasleen Kaur Virdi1, Ritu Kulshrestha2, Amteshwar Singh Jaggi1★★ Corresponding author

  1. 1Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, Punjab, INDIA.
  2. 2Department of Pathology, Vallabhbhai Patel Chest Institute, University of Delhi, New Delhi, INDIA.

CORRESPONDENCE

Amteshwar Singh Jaggi

Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala-147002, Punjab, INDIA.

amteshwarjaggi@yahoo.co.in

Received: 22-04-2021; Revised: 02-06-2021; Accepted: 10-09-2021.

Volume 55, Issue 4 · pp. 1037–1047 · PUBLISHED 2021 · DOI: 10.5530/ijper.55.4.204

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ABSTRACT

Aim: To study the effect of 3-methyladenine and chloroquine phosphate on 3-nitropropionic acid induced Huntington’s disease-like symptoms in mice. Materials and Methods: 3-Nitropropionic acid was administered at the dose of 50 mg/kg, i.p. twice daily for 5 days for inducing Huntington’s disease like symptoms. 3-Methyladenine (15 and 30 mg/kg, i.p.) and chloroquine phosphate (25 and 50 mg/kg, i.p.) were administered 30 min before each 3-nitropropionic acid administration. The motor tests including, rota-rod, beam walking, lateral push test and open-field test, along with memory/cognitive test using object recognition test were performed on day 0, 3 and 6. The role of autophagy was assessed by measuring the levels of LC3II in the brain. Histopathological studies using H&E, nissl staining; and immunohistochemistry of neuron specific enolase and caspase-3 were also performed. Results: Administration of 3-nitropropionic acid caused a decline in the motor functions and cognitive abilities of the animals. The histopathological studies also indicated neuronal injury and neuronal loss in the striatal region. Treatment with 3-methyladenine and chloroquine ameliorated motor and cognitive parameters induced by 3-nitropropionic acid along with prevention of neuronal loss. Moreover, these pharmacological agents ameliorated altered levels of LC3II with 3-methyladenine and chloroquine administration indicated involvement of autophagy. Conclusion: Treatment with 3-methyladenine and chloroquine may improve the symptoms related with Huntington’s disease by preventing 3-nitropropionic acid-induced neurodegeneration possibly by inhibiting autophagy.

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    Virdi, J. K., Kulshrestha, R., & Jaggi, A. S. (2021). Ameliorative Effects of 3-methyladenine and Chloroquine in 3-nitropropionic-induced Huntington’s Disease like Symptoms in Mice. Indian Journal of Pharmaceutical Education and Research, 55(4), 1037–1047. https://doi.org/10.5530/ijper.55.4.204