Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson's disease

Brain Res. 2009 Aug 25:1286:25-31. doi: 10.1016/j.brainres.2009.06.060. Epub 2009 Jun 25.


The high-fat ketogenic diet (KD) leads to an increase of blood ketone bodies (KB) level and has been used to treat refractory childhood seizures for over 80 years. Recent reports show that KD, KB and their components (d-beta-hydroxybutyrate, acetoacetate and acetone) have neuroprotective for acute and chronic neurological disorders. In our present work, we examined whether KD protected dopaminergic neurons of substantia nigra (SN) against 6-hydroxydopamine (6-OHDA) neurotoxicity in a rat model of Parkinson's disease (PD) using Nissl staining and tyrosine hydroxylase (TH) immunohistochemistry. At the same time we measured dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. To elucidate the mechanism, we also measured the level of glutathione (GSH) of striatum. Our data showed that Nissl and TH-positive neurons increased in rats fed with KD compared to rats with normal diet (ND) after intrastriatal 6-OHDA injection, so did DA and its metabolite DOPAC. While HVA had not changed significantly. The change of GSH was significantly similar to DA. We concluded that KD had neuroprotective against 6-OHDA neurotoxicity and in this period GSH played an important role.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / analysis
  • Adrenergic Agents / toxicity
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Brain Chemistry
  • Chromatography, High Pressure Liquid
  • Diet, Ketogenic*
  • Dopamine
  • Glutathione / analysis
  • Glutathione / metabolism*
  • Homovanillic Acid / analysis
  • Immunohistochemistry
  • Nerve Degeneration / diet therapy
  • Nerve Degeneration / etiology
  • Nerve Degeneration / pathology
  • Neurons / metabolism*
  • Neurons / pathology
  • Oxidopamine / toxicity
  • Parkinsonian Disorders / diet therapy*
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / pathology
  • Rats
  • Tyrosine 3-Monooxygenase / metabolism
  • Up-Regulation


  • Adrenergic Agents
  • 3,4-Dihydroxyphenylacetic Acid
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Glutathione
  • Dopamine
  • Homovanillic Acid