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Thymoquinone loaded solid lipid nanoparticles counteracts 3-Nitropropionic acid induced motor impairments and neuroinflammation in rat model of Huntington’s disease

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Abstract

Defect in gene transcription, excitotoxicity, neuroinflammation and oxidative stress are the dominant disease process that causes striatal cell loss with motor abnormalities in Huntington’s disease (HD). Homogeneous pathological reminiscent of HD was extrapolated in the present study using a potent mitochondrial toxin, 3-Nitropropionic acid (3-NP). Administration of 3-NP for 14 days in the present study portends glial cell activation, N-methyl-D-aspartate (NMDA) receptor stimulation, neuroinflammation and motor deficits. The therapeutic strategy in the present study was improvised by formulating thymoquinone, a biologically active compound into a colloidal carrier namely solid lipid nanoparticles. Treatment with 10 and 20 mg/kg b.w of thymoquinone loaded solid lipid nanoparticles (TQ-SLNs) and 80 mg/kg b.w of thymoquinone suspension (TQ-S) showed a significant (P < 0.01) improvement in ATPases function in 3-NP induced animals than TQ-S (40 mg/kg b.w) treated group. TQ-SLNs (10 and 20 mg/kg) treatment also attenuated the overexpression of glial fibrillary acidic protein (GFAP), pro-inflammatory cytokines and p-p65 NFκB nuclear translocation in 3-NP exposed animals. Further, TQ-SLNs treatment desensitizes NR2B-subtype NMDA receptor, improves tyrosine hydroxylase (TH) immune reactive neurons and ameliorated the motor abnormalities in 3-NP intoxicated animals than TQ-S treated group. Hence, the study signifies that the treatment with lower doses of nanoformulated thymoquinone than thymoquinone suspension can efficiently culminate 3-NP induced HD progression in the striatum of male wistar rats.

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Acknowledgements

The first author is grateful to UGC-BSR for the financial support in the form of UGC-JRF Fellowship (Co/Tara/UGC-BSR/Med-Biochem/2015/613 dated 27th October 2015).

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  1. Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, 600 113, India

    Surekha Ramachandran & Sumathi Thangarajan

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  1. Surekha Ramachandran
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  2. Sumathi Thangarajan
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Correspondence to Sumathi Thangarajan.

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Ramachandran, S., Thangarajan, S. Thymoquinone loaded solid lipid nanoparticles counteracts 3-Nitropropionic acid induced motor impairments and neuroinflammation in rat model of Huntington’s disease. Metab Brain Dis 33, 1459–1470 (2018). https://doi.org/10.1007/s11011-018-0252-0

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