Early low-dose ghrelin intervention via miniosmotic pumps could protect against the progressive dopaminergic neuron loss in Parkinson's disease mice

Neurobiol Aging. 2021 May:101:70-78. doi: 10.1016/j.neurobiolaging.2021.01.011. Epub 2021 Jan 20.

Abstract

Ghrelin has been identified as a multifunctional peptide that has a potential application for treating Parkinson's disease (PD). The objective of this study was to assess the effects of subcutaneous administration of low-dose ghrelin via miniosmotic pumps on PD progression. The decreased levels of total and active ghrelin in plasma were rescued by ghrelin administration in PD mice. Interestingly, ghrelin did not affect weight gain in wild-type mice but improved weight loss in PD mice. We observed the attenuation of dopaminergic neuron loss in substantia nigra and a low level of dopamine content in the striatum in PD mice with ghrelin treatment. Ghrelin administration could improve the microenvironment of dopaminergic neurons by inhibiting microglial proliferation and proinflammatory cytokine expression and could enhance cell survival by upregulating Bcl-2/Bax ratio and superoxide dismutase1 protein level in the substantia nigra of PD mice. Subcutaneous administration of low-dose ghrelin could prevent the onset of the progression of PD and also provide a possible method for ghrelin application to cure PD.

Keywords: Apoptosis; Ghrelin; Inflammation; Oxidative stress; Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cellular Microenvironment / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Dopaminergic Neurons / pathology*
  • Ghrelin / administration & dosage*
  • Ghrelin / pharmacology*
  • Inflammation
  • Inflammation Mediators / metabolism
  • Injections, Subcutaneous
  • Mice, Transgenic
  • Microglia / metabolism
  • Microglia / pathology
  • Osmotic Pressure / drug effects*
  • Oxidative Stress / drug effects
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / etiology*
  • Parkinson Disease / pathology
  • Parkinson Disease / prevention & control

Substances

  • Cytokines
  • Ghrelin
  • Inflammation Mediators