PMID- 25108167
OWN - NLM
STAT- MEDLINE
DCOM- 20150608
LR  - 20140915
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 277
DP  - 2014 Sep 26
TI  - Neuroprotective effect of metformin in MPTP-induced Parkinson's disease in mice.
PG  - 747-54
LID - S0306-4522(14)00619-8 [pii]
LID - 10.1016/j.neuroscience.2014.07.046 [doi]
AB  - 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.
CI  - Copyright (c) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Patil, S P
AU  - Patil SP
AD  - Department of Pharmaceutical Sciences and Technology, Institute of Chemical 
      Technology, Nathalal Parekh Marg, Matunga, Mumbai 19, Maharashtra, India.
FAU - Jain, P D
AU  - Jain PD
AD  - Department of Pharmaceutical Sciences and Technology, Institute of Chemical 
      Technology, Nathalal Parekh Marg, Matunga, Mumbai 19, Maharashtra, India.
FAU - Ghumatkar, P J
AU  - Ghumatkar PJ
AD  - Department of Pharmaceutical Sciences and Technology, Institute of Chemical 
      Technology, Nathalal Parekh Marg, Matunga, Mumbai 19, Maharashtra, India.
FAU - Tambe, R
AU  - Tambe R
AD  - Department of Pharmaceutical Sciences and Technology, Institute of Chemical 
      Technology, Nathalal Parekh Marg, Matunga, Mumbai 19, Maharashtra, India.
FAU - Sathaye, S
AU  - Sathaye S
AD  - Department of Pharmaceutical Sciences and Technology, Institute of Chemical 
      Technology, Nathalal Parekh Marg, Matunga, Mumbai 19, Maharashtra, India. 
      Electronic address: sadhanasathaye@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140807
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Antioxidants)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 9100L32L2N (Metformin)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Catalase/metabolism
MH  - Glutathione/metabolism
MH  - Lipid Peroxidation/drug effects/physiology
MH  - MPTP Poisoning/*drug therapy/metabolism/pathology
MH  - Male
MH  - Metformin/*pharmacology
MH  - Mice
MH  - Motor Activity/drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - Oxidative Stress/drug effects/physiology
MH  - Random Allocation
MH  - Rotarod Performance Test
MH  - Substantia Nigra/drug effects/metabolism/pathology
MH  - Superoxide Dismutase/metabolism
MH  - Tyrosine 3-Monooxygenase/metabolism
OTO - NOTNLM
OT  - Parkinson's disease
OT  - metformin
OT  - neuroprotective
OT  - neurotrophic
OT  - oxidative stress
EDAT- 2014/08/12 06:00
MHDA- 2015/06/09 06:00
CRDT- 2014/08/10 06:00
PHST- 2014/03/28 00:00 [received]
PHST- 2014/07/20 00:00 [revised]
PHST- 2014/07/21 00:00 [accepted]
PHST- 2014/08/10 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2015/06/09 06:00 [medline]
AID - S0306-4522(14)00619-8 [pii]
AID - 10.1016/j.neuroscience.2014.07.046 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Sep 26;277:747-54. doi: 10.1016/j.neuroscience.2014.07.046. 
      Epub 2014 Aug 7.