Acyl-Ghrelin Attenuates Neurochemical and Motor Deficits in the 6-OHDA Model of Parkinson's Disease

Cell Mol Neurobiol. 2023 Jul;43(5):2377-2384. doi: 10.1007/s10571-022-01282-9. Epub 2022 Sep 15.

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.

Keywords: 6-OHDA; Acyl-ghrelin; Parkinson’s disease.

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Dopamine
  • Dopaminergic Neurons
  • Mice
  • Oxidopamine
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / pathology
  • Rats

Substances

  • Oxidopamine
  • Dopamine
  • acyl-ghrelin
  • Amphetamine