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Int J Mol Med. 2013 Oct;32(4):883-91. doi: 10.3892/ijmm.2013.1450. Epub 2013 Jul 18.

Selegiline rescues gait deficits and the loss of dopaminergic neurons in a subacute MPTP mouse model of Parkinson's disease.

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  • 1Department of Neurology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China. zhaoqingmedsci@126.com

Abstract

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.

[PubMed - indexed for MEDLINE]
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