Neuroprotective effect of metformin in MPTP-induced Parkinson's disease in mice

Neuroscience. 2014 Sep 26;277:747-54. doi: 10.1016/j.neuroscience.2014.07.046. Epub 2014 Aug 7.


Metformin a well known antidiabetic drug has been recently investigated and proposed to promote neurogenesis and enhance the spatial memory formation. In the present study, we aim to investigate the neuroprotective effect of metformin with respect to Parkinson's disease (PD). MPTP (Sigma-Aldrich, St. Louis, MO, USA) (25mg/kg) along with Probenecid (250 mg/kg) was administrated for five consecutive days to induce Parkinsonism in mice. Metformin 500 mg/kg was administrated orally for 21 days. Motor co-ordination and locomotor activities were evaluated by rotarod and open-field tests. The oxidative stress levels were assessed by estimating the activity of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and lipid peroxidation (LPO) specifically in the midbrain. Dopaminergic degeneration was evaluated by analyzing the tyrosine hydroxylase (TH) by immunostaining and nissl staining of the substantia nigra (SN) region of the brain. In addition brain-derived neurotrophic factor (BDNF) was also estimated. Our findings demonstrated that long-term metformin treatment resulted in significant improvement of the locomotor and muscular activities in MPTP-treated mice than acute treatment. Metformin treatment significantly improved the antioxidant activity as compared to MPTP-treated group. TH-positive cells decreased up to 16% in MPTP-treated mice as compared to normal mice (P<0.001) and were found to be protected from degeneration in metformin-treated mice (47%, P<0.01). Interestingly, BDNF levels were found to be significantly elevated in metformin treatment group as compared to MPTP treatment mice (P<0.001). In conclusion, metformin possesses neuroprotective activity and provides preclinical support for therapeutic prospective of this compound in the treatment of PD.

Keywords: Parkinson’s disease; metformin; neuroprotective; neurotrophic; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Antioxidants / pharmacology
  • Brain-Derived Neurotrophic Factor / metabolism
  • Catalase / metabolism
  • Glutathione / metabolism
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology
  • MPTP Poisoning / drug therapy*
  • MPTP Poisoning / metabolism
  • MPTP Poisoning / pathology
  • Male
  • Metformin / pharmacology*
  • Mice
  • Motor Activity / drug effects
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Random Allocation
  • Rotarod Performance Test
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Superoxide Dismutase / metabolism
  • Tyrosine 3-Monooxygenase / metabolism


  • Antioxidants
  • Brain-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • Metformin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Catalase
  • Tyrosine 3-Monooxygenase
  • Superoxide Dismutase
  • Glutathione