Cannabidiol Alleviates the Damage to Dopaminergic Neurons in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinson's Disease Mice Via Regulating Neuronal Apoptosis and Neuroinflammation

Neuroscience. 2022 Aug 21:498:64-72. doi: 10.1016/j.neuroscience.2022.06.036. Epub 2022 Jul 2.

Abstract

Parkinson's disease (PD) is a complex and multifactorial neurodegenerative disease. The main pathological feature of PD is the loss or apoptosis of dopaminergic neurons in the substantia nigra (SN). This study aimed to investigate the protective effect of cannabidiol (CBD) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal dopamine injury by inhibiting neuroinflammation, which was one of the factors that cause neuronal apoptosis. Male SPF C57BL/6 mice were used to create a PD model by administering MPTP intraperitoneally for seven days and treated by oral administration of CBD for 14 days. Behaviorally, CBD improved cognitive dysfunction and increased the number of spontaneous locomotion in PD mice. Biochemically, CBD increased the levels of 5-HT, DA and IL-10, and decreased the contents of TNF-α, IL-1β and IL-6. Pathologically, CBD increased the expression of tyrosine hydroxylase (TH). Mechanistically, CBD up-regulated the expression of Bcl-2, down-regulated the levels of Bax and Caspase-3, and repressed the expression of NLRP3/caspase-1/IL-1β inflammasome pathway. In summary, CBD has a therapeutic effect on MPTP-induced PD mice by inhibiting the apoptosis of dopaminergic neurons and neuroinflammation. Therefore, CBD is a potential candidate for PD therapy.

Keywords: Parkinson’s disease; apoptosis; cannabidiol; dopaminergic neurons; neuroinflammation; substantia nigra.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Apoptosis
  • Cannabidiol*
  • Disease Models, Animal
  • Dopaminergic Neurons
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurodegenerative Diseases*
  • Neuroinflammatory Diseases
  • Neuroprotective Agents*
  • Parkinson Disease*
  • Pyrrolidines
  • Substantia Nigra

Substances

  • Neuroprotective Agents
  • Pyrrolidines
  • Cannabidiol
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine