Neuroprotective effects of prior limb use in 6-hydroxydopamine-treated rats: possible role of GDNF.
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.
Cohen
Ann D
AD
Department of Neurology and Center for Neuroscience, University of Pittsburgh, Philadelphia, USA.
Tillerson
Jennifer L
JL
Smith
Amanda D
AD
Schallert
Timothy
T
Zigmond
Michael J
MJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002370:Casts, Surgical; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005552:Forelimb / Q000503:physiopathology; D007839:Functional Laterality; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007103:Immobilization / Q000502:physiology; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors / Q000378:metabolism*; D016627:Oxidopamine / Q000008:administration & dosage / Q000494:pharmacology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine