Acyl-ghrelin attenuates neurochemical and motor deficits in the 6-OHDA model of Parkinson’s Disease

Rees, Daniel, Beynon, Amy L., Lelos, Mariah J. ORCID: https://orcid.org/0000-0001-7102-055X, Smith, Gaynor A. ORCID: https://orcid.org/0000-0003-4332-8383, Roberts, Luke D., Phelps, Lyndsey, Dunnett, Stephen B. ORCID: https://orcid.org/0000-0003-1826-1578, Morgan, Alwena H., Brown, Rowan M., Wells, Timothy ORCID: https://orcid.org/0000-0003-3618-0595 and Davies, Jefrey S. 2023. Acyl-ghrelin attenuates neurochemical and motor deficits in the 6-OHDA model of Parkinson’s Disease. Cellular and Molecular Neurobiology 43 , pp. 2377-2384. 10.1007/s10571-022-01282-9

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Abstract

The feeding-related hormone, acyl-ghrelin, protects dopamine neurones in murine 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-based models of experimental Parkinson’s disease (PD). However, the potential protective effect of acyl-ghrelin on substantia nigra pars compacta (SNpc) dopaminergic neurones and consequent behavioural correlates in the more widely used 6-hydroxydopamine (6-OHDA) rat medial forebrain bundle (MFB) lesion model of PD are unknown. To address this question, acyl-ghrelin levels were raised directly by mini-pump infusion for 7 days prior to unilateral injection of 6-OHDA into the MFB with assessment of amphetamine-induced rotations on days 27 and 35, and immunohistochemical analysis of dopaminergic neurone survival. Whilst acyl-ghrelin treatment was insufficient to elevate food intake or body weight, it attenuated amphetamine-induced circling behaviour and SNpc dopamine neurone loss induced by 6-OHDA. These data support the notion that elevating circulating acyl-ghrelin may be a valuable approach to slow or impair progression of neurone loss in PD.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Springer
ISSN:	0272-4340
Date of First Compliant Deposit:	4 October 2022
Date of Acceptance:	30 August 2022
Last Modified:	20 Jul 2023 18:20
URI:	https://orca.cardiff.ac.uk/id/eprint/153051

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