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Published on:November 2021
Indian Journal of Pharmaceutical Education and Research, 2021; 55(4):1037-1047
Original Article | doi:10.5530/ijper.55.4.204

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


Authors and affiliation (s):

Jasleen Kaur Virdi1, Ritu Kulshrestha2, Amteshwar Singh Jaggi1,*

1Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, Punjab, INDIA.

2Department of Pathology, Vallabhbhai Patel Chest Institute, University of Delhi, New Delhi, INDIA.

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. 

Key words: Huntington’s disease, 3-nitropropionic acid, Autophagy, Chloroquine phosphate, 3-methyladenine.

 




 

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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.

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