Phosphatidylinositol 3-kinase/Akt signaling pathway mediates acupuncture-induced dopaminergic neuron protection and motor function improvement in a mouse model of Parkinson's disease

Int J Neurosci. 2011 Oct;121(10):562-9. doi: 10.3109/00207454.2011.591515. Epub 2011 Jul 19.

Abstract

It has been reported that acupuncture treatment reduced dopaminergic neuron degeneration in Parkinson's disease (PD) models. However, the mechanistic pathways underlying, such neuroprotection, are poorly understood. Here, we investigated the effects and the underlying mechanism of acupuncture in a mouse model of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). First, we observed that MPTP-induced impairment of Akt activation, but not MPTP-induced c-Jun activation, was effectively restored by acupuncture treatment in the substantia nigra. Furthermore, we demonstrated for the first time that the brain-specific blockade of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, by intranasal administration of LY294002, a specific inhibitor of PI3K/Akt signaling pathway, significantly blocked acupuncture-induced dopaminergic neuron protection and motor function improvement. Our results provide evidence that PI3K/Akt signaling pathway may play a central role in the mechanism underlying acupuncture-induced benefits in Parkinsonian mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acupuncture Points
  • Acupuncture*
  • Administration, Intranasal
  • Animals
  • Chromones / administration & dosage
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / physiology*
  • Enzyme Inhibitors / administration & dosage
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • MPTP Poisoning* / metabolism
  • MPTP Poisoning* / pathology
  • MPTP Poisoning* / prevention & control
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morpholines / administration & dosage
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-jun / metabolism
  • Rotarod Performance Test
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Substantia Nigra / cytology*
  • Substantia Nigra / drug effects
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • Proto-Oncogene Proteins c-jun
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Tyrosine 3-Monooxygenase
  • Phosphatidylinositol 3-Kinases