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. 2018 Nov-Dec;50(6):309-319.
doi: 10.4103/ijp.IJP_11_18.

Neuroprotective effect of solanesol against 3-nitropropionic acid-induced Huntington's disease-like behavioral, biochemical, and cellular alterations: Restoration of coenzyme-Q10-mediated mitochondrial dysfunction

Sidharth Mehan  1 , Vikramdeep Monga  2 , Manju Rani  3 , Rajesh Dudi  3 , Krishna Ghimire  4
Affiliations

Neuroprotective effect of solanesol against 3-nitropropionic acid-induced Huntington's disease-like behavioral, biochemical, and cellular alterations: Restoration of coenzyme-Q10-mediated mitochondrial dysfunction

Sidharth Mehan et al. Indian J Pharmacol. 2018 Nov-Dec.

Abstract

Objective: The aim of the present study was to evaluate the solanesol (SNL)-mediated coenzyme-Q10 restoration to ameliorate 3-nitropropionic (3-NP)-induced behavioral, biochemical, and histological changes which resemble Huntington's disease (HD)-like symptoms in men.

Materials and methods: Various behavioral and biochemical parameters were carried out to evaluate the activity of SNL on 3-NP-treated rats. To determine the therapeutic significance of SNL on HD, different behavioral tests such as memory task, locomotor activity, grip strength, and beam cross and some biochemical test along with histopathological findings were done.

Results: Chronic 3-NP, 10 mg/kg i.p., caused physical and mental abnormalities in animals, including memory impairment, weak grip strength, abnormal posture, and cognitive deficit. Biochemical analysis of brain homogenate in 3-NP-treated rats showed altered mitochondrial complexes, oxidative stress, and elevated lipid biomarkers. Neurohistological alterations of hippocampus, basal ganglia, and cerebral cortex of 3-NP-treated rats exhibit severe neuronal space, irregular damaged cells, and dense pyknotic nuclei-associated marked focal diffused gliosis. SNL administered for 15 days significantly improved motor performance and cognitive behavior task and restored the histopathological changes. Further, SNL treatment significantly improved mitochondrial complexes such as coenzyme-Q10 enzyme activity and attenuated inflammatory and oxidative damage of rat brain.

Conclusion: In the present research work, SNL (5, 10, and 15 mg/kg p.o.) provided notable neuroprotective effect, which was confirmed by behavioral paradigms and biochemical test. It restored the behavioral and biochemical alteration caused by 3-NP and confirmed the strong neuroprotective mechanism of SNL in 3-NP-intoxicated memory and cognitive abnormalities.

Keywords: 3-nitropropionic acid; Coenzyme-Q10; Huntington's disease; mitochondrial dysfunction; solanesol.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
The design of the treatment schedule and the interval for estimation of various behavioral and biochemical estimations
Figure 2
Figure 2
Effect of solanesol on transfer latency of rats using Morris water maze. Values are mean ± standard deviation (n= 6), *signifies P< 0.05 as compared to normal and solanesol per se,#P< 0.05 versus 3-nitropropionic,#@P< 0.05 as compared to SNL (5 + 3-nitropropionic) and solanesol (10 + 3-nitropropionic)
Figure 3
Figure 3
Effect of solanesol on time spent in target quadrant of rats using Morris water maze. Values are mean ± standard deviation (n= 6), *signifies P< 0.05 as compared to normal and solanesol per se,#P< 0.05 versus 3-nitropropionic,#@P< 0.05 as compared to solanesol (5 + 3-nitropropionic) and solanesol (10 + 3-nitropropionic)
Figure 4
Figure 4
Effect of solanesol on locomotor activity in 3-nitropropionic treated rats. Values are mean ± standard deviation (n= 6), *signifies P< 0.05 as compared to normal and solanesol per se,#P< 0.05 versus 3-nitropropionic,#@P< 0.05 as compared to solanesol (10 + 3-nitropropionic) and solanesol (15 + 3-nitropropionic)
Figure 5
Figure 5
Effect of solanesol on grip strength in 3-nitropropionic treated rats. Values are mean ± standard deviation (n= 6), *signifies P< 0.05 as compared to normal and solanesol per se,#P< 0.05 versus 3-nitropropionic,#@P< 0.05 as compared to solanesol (10 + 3-nitropropionic) and solanesol (15 + 3-nitropropionic)
Figure 6
Figure 6
Effect of solanesol on transfer latency of rats using elevated plus maze. Values are mean ± standard deviation (n= 6), *signifies P< 0.05 as compared to normal and solanesol per se,#P< 0.05 versus 3-nitropropionic,#@P< 0.05 as compared to solanesol (10 + 3-nitropropionic) and SNL (15 + 3-nitropropionic)
Figure 7
Figure 7
Effect of solanesol on balance beam-walking performance in 3-nitropropionic-treated rats (No. of slips). Values are mean ± standard deviation (n= 6), *signifies P< 0.05 as compared to normal and solanesol per se,#P< 0.05 versus 3-nitropropionic,#@P< 0.05 as compared to solanesol (10 + 3-nitropropionic) and solanesol (15 + 3-nitropropionic)
Figure 8
Figure 8
Effect of solanesol on balance beam-walking performance in 3-nitropropionic-treated rats (neurological score).Values are mean ± standard deviation (n= 6), *signifies P< 0.05 as compared to normal and solanesol per se,#P< 0.05 versus 3-nitropropionic,#@P< 0.05 as compared to solanesol (10 + 3-nitropropionic) and solanesol (15 + 3-nitropropionic)
Figure 9
Figure 9
Panel A1 (basal ganglia), panel A2 (cortex) and panel A3 (hippocampus): photomicrographs of H and E-stained brain sections of normal rats
Figure 10
Figure 10
Panel B1 (striatum), panel B2 (cortex) and panel B3 (hippocampus): photomicrographs of H and E-stained brain sections of solanesol per se treated rats
Figure 11
Figure 11
Panel C1 (basal ganglia), panel C2 (cortex) and panel C3 (hippocampus): photomicrographs of H and E-stained brain sections of intracranial hemorrhage-treated rats
Figure 12
Figure 12
Panel D1 (basal ganglia), panel D2 (cortex) and panel D3 (hippocampus): photomicrographs of H and E-stained brain sections of solanesol 60 mg/kg p.o. treated rats
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