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

Publisher Website
Google Scholar
Abstract
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.