PMID- 23877198
OWN - NLM
STAT- MEDLINE
DCOM- 20140327
LR  - 20151119
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 32
IP  - 4
DP  - 2013 Oct
TI  - Selegiline rescues gait deficits and the loss of dopaminergic neurons in a 
      subacute MPTP mouse model of Parkinson's disease.
PG  - 883-91
LID - 10.3892/ijmm.2013.1450 [doi]
AB  - The monoamine oxidase type-B (MAO-B) inhibitor, selegiline, is often recommended 
      as a first-line treatment for Parkinson's disease (PD) and has been shwon to 
      possess neuroprotective effects. The aim of the present study was to determine 
      whether selegiline increases the levels of the neurotrophic factors (NTFs), glial 
      cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic 
      factor (BDNF), and whether it rescues motor dysfunction and the loss of 
      dopaminergic neurons in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 
      (MPTP)-induced lesions. We found that the oral administration of selegiline (1.0 
      mg/kg/day for 14 days) successfully suppressed the MPTP-induced reduction of 
      nigral dopaminergic neurons and striatal fibers (192.68 and 162.76% of 
      MPTP-exposed animals, respectively; both P<0.001). Moreover, improvements in gait 
      dysfunction were observed after 7 and 14 days of a low dose of selegiline that is 
      reported not to inhibit MAO‑B. Furthermore, there was a significant increase in 
      GDNF and BDNF mRNA (2.10 and 2.75-fold) and protein levels (143.53 and 157.05%) 
      in the selegiline-treated mice compared with the saline-treated MPTP-exposed 
      mice. In addition, the Bax/Bcl-2 gene and protein expression ratios were 
      significantly increased in the MPTP-exposed mice, and this effect was reversed by 
      selegiline. Correlation analysis revealed that gait measurement and GDNF/BDNF 
      levels positively correlated with the number of dopaminergic neurons. These 
      findings demonstrate that selegiline has neurorescue effects that are possibly 
      associated with the induction of NTFs and anti-apoptotic genes.
FAU - Zhao, Qing
AU  - Zhao Q
AD  - Department of Neurology, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, PR China. zhaoqingmedsci@126.com
FAU - Cai, Dingfang
AU  - Cai D
FAU - Bai, Yu
AU  - Bai Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130718
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Bax protein, mouse)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 2K1V7GP655 (Selegiline)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects
MH  - Animals
MH  - Disease Models, Animal
MH  - Dopaminergic Neurons/*drug effects/pathology
MH  - Gait/*drug effects
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monoamine Oxidase
MH  - Monoamine Oxidase Inhibitors/*pharmacology
MH  - Neurons/drug effects/metabolism
MH  - Neuroprotective Agents/pharmacology
MH  - Parkinson Disease/*drug therapy
MH  - RNA, Messenger/genetics/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Selegiline/*administration & dosage
MH  - bcl-2-Associated X Protein/genetics/metabolism
EDAT- 2013/07/24 06:00
MHDA- 2014/03/29 06:00
CRDT- 2013/07/24 06:00
PHST- 2013/04/19 00:00 [received]
PHST- 2013/07/10 00:00 [accepted]
PHST- 2013/07/24 06:00 [entrez]
PHST- 2013/07/24 06:00 [pubmed]
PHST- 2014/03/29 06:00 [medline]
AID - 10.3892/ijmm.2013.1450 [doi]
PST - ppublish
SO  - Int J Mol Med. 2013 Oct;32(4):883-91. doi: 10.3892/ijmm.2013.1450. Epub 2013 Jul 
      18.