NEUROPROTECTION BY VALPROIC ACID IN AN INTRASTRIATAL ROTENONE MODEL OF PARKINSON′S DISEASE

被引:33
作者
Carriere, C. H. [1 ]
Kang, N. H. [1 ]
Niles, L. P. [1 ]
机构
[1] McMaster Univ, Dept Psychiat & Behav Neurosci, Fac Hlth Sci, Hamilton, ON L8S 4L8, Canada
基金
加拿大健康研究院;
关键词
Parkinson ' s disease; rotenone; intrastriatal; valproic acid; neuroprotection; HISTONE DEACETYLASE INHIBITION; NIGROSTRIATAL DOPAMINE SYSTEM; RAT MODEL; ALPHA-SYNUCLEIN; NEUROTROPHIC FACTORS; FOREBRAIN-BUNDLE; MOOD STABILIZER; NEURONS; INFUSION; BRAIN;
D O I
10.1016/j.neuroscience.2014.02.028
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Rotenone, which is used as a pesticide and ticide, has been shown to cause systemic inhibition of chondrial complex I activity, with consequent of dopaminergic neurons within the substantia nigra striatum, as observed in Parkinson ' s disease. A novel striatal rotenone model of Parkinson ' s disease was used examine the neuroprotective effects of valproic acid (VPA) which is known to upregulate neurotrophic factors other protective proteins in the brain. Sham or lesioned were treated with either vehicle or VPA at a dose of 4 mg/in drinking water. The right striatum was lesioned by sion of rotenone at three sites (2 mu g/site) along its caudal axis. A forelimb asymmetry (cylinder) test a significant (p < 0.01) decrease in use of the forelimb in rotenone-lesioned animals, in the third post-lesioning, which was abolished by VPA treatment. ilarly, a significant (p < 0.01) and persistent increase in of the ipsilateral forelimb in lesioned animals over 4 weeks of testing, was not seen in animals treated VPA. Results of the asymmetry test illustrate that tal infusion of rotenone causes contralateral motor tion, which is blocked by VPA. The significant increase ipsilateral forelimb use has not been previously, and presumably represents a response in lesioned animals. Six weeks post-surgery, mals were sacrificed by transcardial perfusion. immunohistochemical examination revealed a decrease tyrosine hydroxylase immunoreactivity within the and substantia nigra of rotenone-lesioned animals. treatment attenuated the decrease in tyrosine in the striatum and abolished it in the substantia nigra. eological cell counting indicated a significant (p < 0.05) decrease in tyrosine hydroxylase-positive dopamine rons in the substantia nigra of rotenone-lesioned which was confirmed by Nissl staining. Importantly, loss of dopamine neurons in rotenone-lesioned was blocked by chronic VPA treatment. These strongly support the therapeutic potential of VPA Parkinson's disease. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:114 / 121
页数:8
相关论文
共 40 条
[1]   Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats [J].
Alam, M ;
Schmidt, WJ .
BEHAVIOURAL BRAIN RESEARCH, 2002, 136 (01) :317-324
[2]   A highly reproducible rotenone model of Parkinson's disease [J].
Cannon, Jason R. ;
Tapias, Victor ;
Na, Hye Mee ;
Honick, Anthony S. ;
Drolet, Robert E. ;
Greenamyre, J. Timothy .
NEUROBIOLOGY OF DISEASE, 2009, 34 (02) :279-290
[3]   Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes [J].
Chen, P-S ;
Peng, G-S ;
Li, G. ;
Yang, S. ;
Wu, X. ;
Wang, C-C ;
Wilson, B. ;
Lu, R-B ;
Gean, P-W ;
Chuang, D-M ;
Hong, J-S .
MOLECULAR PSYCHIATRY, 2006, 11 (12) :1116-1125
[4]   Therapeutic Potential of Mood Stabilizers Lithium and Valproic Acid: Beyond Bipolar Disorder [J].
Chiu, Chi-Tso ;
Wang, Zhifei ;
Hunsberger, Joshua G. ;
Chuang, De-Maw .
PHARMACOLOGICAL REVIEWS, 2013, 65 (01) :105-142
[5]   Valproic acid regulates catecholaminergic pathways by concentration-dependent threshold effects on TH mRNA synthesis and degradation [J].
D'Souza, Antoni ;
Onem, Eylem ;
Patel, Pranav ;
La Gamma, Edmund F. ;
Nankova, Bistra B. .
BRAIN RESEARCH, 2009, 1247 :1-10
[6]   Parkinson's disease: Mechanisms and models [J].
Dauer, W ;
Przedborski, S .
NEURON, 2003, 39 (06) :889-909
[7]   Neuroprotection by GDNF in the ischemic brain [J].
Duarte, Emilia P. ;
Curcio, Michele ;
Canzoniero, Lorella M. ;
Duarte, Carlos B. .
GROWTH FACTORS, 2012, 30 (04) :242-257
[8]   An intermittent, controlled-rate, slow progressive degeneration model of Parkinson's disease: antiparkinson effects of Sinemet and protective effects of methylphenidate [J].
Fleming, SM ;
Delville, Y ;
Schallert, T .
BEHAVIOURAL BRAIN RESEARCH, 2005, 156 (02) :201-213
[9]   Dose-dependent memory effects and cerebral volume changes after in utero exposure to valproate in the rat [J].
Frisch, Christian ;
Huesch, Kerstin ;
Angenstein, Frank ;
Kudin, Alexei ;
Kunz, Wolfram ;
Elger, Christian E. ;
Helmstaedter, Christoph .
EPILEPSIA, 2009, 50 (06) :1432-1441
[10]   Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells [J].
Göttlicher, M ;
Minucci, S ;
Zhu, P ;
Krämer, OH ;
Schimpf, A ;
Giavara, S ;
Sleeman, JP ;
Lo Coco, F ;
Nervi, C ;
Pelicci, PG ;
Heinzel, T .
EMBO JOURNAL, 2001, 20 (24) :6969-6978