Neuroprotective effects of prior limb use in 6-hydroxydopamine-treated rats: possible role of GDNF

被引:185
作者
Cohen, AD
Tillerson, JL
Smith, AD
Schallert, T
Zigmond, MJ
机构
[1] Univ Pittsburgh, Dept Neurol, Philadelphia, PA USA
[2] Univ Pittsburgh, Ctr Neurosci, Philadelphia, PA USA
[3] Univ Texas, Inst Neurosci, Austin, TX 78712 USA
[4] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA
关键词
behavior; exercise; GDNF; neurotrophic factor; Parkinson's disease; striatum;
D O I
10.1046/j.1471-4159.2003.01657.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) causes a loss of dopamine (DA) in the ipsilateral striatum and contralateral motor deficits. However, if a cast is placed on the ipsilateral limb during the first 7 days following 6-OHDA infusion, forcing the animal to use its contralateral limb, both the behavioral and neurochemical deficits are reduced. Here, we examine the effect of forced reliance on a forelimb during the 7 days prior to ipsilateral infusion of 6-OHDA on the deficits characteristic of this lesion model. Casted animals displayed no behavioral asymmetries as measured 14-28 days postlesion and a marked attenuation in the loss of striatal DA and its metabolites at 30 days. In addition, animals receiving a unilateral cast alone had an increase in glial cell-line derived neurotrophic factor (GDNF) protein in the striatum corresponding to the overused limb. GDNF increased within 1 day after the onset of casting, peaked at 3 days, and returned to baseline within 7 days. These results suggest that preinjury forced limb-use can prevent the behavioral and neurochemical deficits to the subsequent administration of 6-OHDA and that this may be due in part to neuroprotective effects of GDNF.
引用
收藏
页码:299 / 305
页数:7
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