Withaferin A (WA) was evaluated for its neuro-protective efficacy on ageing induced striatal dopamine (DA) and behavioural changes in aged rats. Wistar albino rats were divided into group I – young (3 months), Group II – aged (24 months), Group III – aged rats supplemented with WA (50 mg/kg b.w once in a day for 30 days) and Group IV – young rats supplemented with WA (50 mg/kg b.w). The HPLC assay revealed significant decline in the levels of DA and homovanillic acid (HVA) in substantia nigra (SN) and striatum (ST) of aged rat. A marked decline in motor activity of aged rat was observed through open field, beam walking and grid walking motor experiments. These results indicate that ageing reduces nigro-striatal activity as well as nigro-striatal DA levels. Interestingly, the administration of WA (50 mg\kg b.w) resulted in a substantial resurge of DA and HVA in SN and ST and a significant reversal of motor impairment in aged rats. This study is the first report that evidently determines the neuro-protective efficacy of WA on dopaminergic system of SN and ST in aged rats.

Keywords:
Ageing, Dopamine, Withaferin-A, Striatum, Substantia nigra
1.
Hindle JV: Ageing, neurodegeneration and Parkinson’s disease. Age Ageing 2010; 39: 156–161.
2.
Ponzio F, Achilli G, Calderini G, Ferretti P, Perego C, Toffano G, et al: Depletion and recovery of neuronal monoamine storage in rats of different ages treated with reserpine. Neurobiol Aging 1984; 5: 101–104.
3.
Ureshino RP, Costa AJ, Pereira S, Erustes AG, Jose G, Sinigaglia-coimbra R, et al: Effects of aging in the striatum and substantia nigra of a Parkinson’s disease animal model. Toxicol Pathol 2018; 46: 348–358.
4.
Justice JN, Carter CS, Beck HJ, Gioscia-ryan RA, Mcqueen M, Enoka RM, et al: Battery of behavioral tests in mice that models age-associated changes in human motor function. Age (Dordr) 2014; 36: 583–595.
5.
Altun M, Bergman E, Edström E, Johnson H, Ulfhake B: Behavioral impairments of the aging rat. Physiol Behav 2007; 92: 911–923.
6.
Naoi M, Maruyama W: Cell death of dopamine neurons in aging and Parkinson’s disease. Mech Ageing Dev 1999; 111: 175–188.
7.
Reeve AK, Grady JP, Cosgrave EM, Bennison E, Chen C, Hepplewhite PD, et al: Mitochondrial Dysfunction within the Synapses of Substantia Nigra Neurons in Parkinson’s Disease. NPJ Park Dis. Springer, 2018, vol 4, p 9. http://www.nature.com/articles/s41531-018-0044-6.
8.
Kulkarni SK, Dhir A: Withania somnifera: an Indian ginseng. Prog Neuropsychopharmacology Biol Psychiatry 2008; 32: 1093–1105.
9.
Katual MK, Harikumar SL: Persistent management of Parkinson’s disease with withania somnifera: an outlook. World J Pharm Sci 2017; 6: 382–401.
10.
Durg S, Dhadde SB, Vandal R, Shivakumar BS, Charan CS: Withania somnifera (Ashwagandha) in neurobehavioural disorders induced by brain oxidative stress in rodents: a systematic review and meta-analysis. J Pharm Pharmacol 2015; 67: 879–899.
11.
Uddin Q, Samiulla L, Singh VK, Jamil SS: Phytochemical and pharmacological profile of Withania somnifera dunal: a review. J Appl Pharm Sci 2012; 2: 170–175.
12.
CCAC: Guide to the Care and Use of Experimental Animals, Volume 2, Volume 1, The Canadian Veterinary Journal, 1993, pp 212.
13.
Ijomone OM, Olaibi OK, Biose IJ, Mba C, Umoren KE, Nwoha PU: Performance of motor associated behavioural tests following chronic nicotine administration. Ann Neurosci 2014; 21: 42–46.
14.
RajaSankar S, Manivasagam T, Surendran S: Ashwagandha leaf extract: a potential agent in treating oxidative damage and physiological abnormalities seen in a mouse model of Parkinson's disease. Neurosci Lett 2009; 454: 11–15.
15.
Chao OY, Pum ME, Li JS, Huston JP: The grid-walking test: assessment of sensorimotor deficits after moderate or severe dopamine depletion by 6-hydroxydopamine lesions in the dorsal striatum and medial forebrain bundle. Neuroscience 2012; 202: 318–325.
16.
Ravindran R, Devi RS, Samson J, Senthilvelan M: Noise-Stress-Induced Brain Neurotransmitter Changes and the Effect of Ocimum sanctum (Linn) Treatment in Albino Rats. J Pharmacol Sci 2005; 98: 354–360. http://joi.jlc.jst.go.jp/JST.JSTAGE/jphs/FP0050127?from=CrossRef.
17.
Zar JH: Biostatistical Analysis. Englewood Cliffs, NJ: Prentice-Hall, 1974, p 620.
18.
Zaeem, Siddiqi, Thomas, Kemper, Robert, Killiany: Age related neuronal loss from the substantia nigra-pars compacta and ventral tegmental area of rhesus monkey. J Neuropathol Exp Neurol 1999; 58: 959–971.
19.
McNeill TH, Koek LL: Differential effects of advancing age on neurotransmitter cell loss in the substantia nigra and striatum of C57BL/6N mice. Brain Res 1990; 521: 107–117.
20.
RajaSankar S, Manivasagam T, Sankar V, Prakash S, Muthusamy R, Krishnamurti A, et al: Withania somnifera root extract improves catecholamines and physiological abnormalities seen in a Parkinson's disease model mouse. J Ethnopharmacol 2009; 125: 369–373.
21.
Seibenhener ML, Wooten MC: Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp 2015; 96:e52434.
22.
Allbutt HN, Henderson JM: Use of the narrow beam test in the rat, 6-hydroxydopamine model of Parkinson’s disease. J Neurosci Methods 2007; 159: 195–202.
23.
Reeve A, Simcox E, Turnbull D: Ageing and Parkinson’s disease: why is advancing age the biggest risk factor? Ageing Res Rev 2014; 14: 19–30.
24.
Ureshino RP, Bertoncini CR, Fernandes MJS, Abdalla FMF, Porto CS, Hsu Y, et al: Alterations in calcium signaling and a decrease in Bcl-2 expression: possible correlation with apoptosis in aged striatum. J Neurosci Res 2010; 447: 438–447.
25.
Murugan, S, M A, R D, Deepapriya K, G N, et al: A Study on the Efficacy of Withaferin-A in Reducing Oxidative Stress Against DEN Induced Hepatocellular Carcinoma. IOSR J Dent Med Sci Ver II 2015; 14: 23–31. www.iosrjournals.org.
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2018
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