Protective effects of intracerebral adenoviral-mediated GDNF gene transfer in a rat model of Parkinson's disease.
This study focuses on the potential protective effects of intracerebral adeno-viral mediated glial cell line derived neurotrophic factor (GDNF) gene transfer in a rat model of Parkinson's disease (PD). Thirty-five SD rats were divided into three groups to receive perinigral injections of recombinant adenovirus encoding GDNF (Ad-GDNF), LacZ (Ad-LacZ) or PBS, respectively. One week later, an intrastriatal injection of 6-hydroxydopamine (6-OHDA) was administered to induce the progressive degeneration of dopaminergic neurons. Immunohistochemistry showed that GDNF treatment prior to neuronal damage could promote survival and morphological recovery of tyrosine hydroxylase (TH)-positive neurons in the midbrain. Approximately 70% of nigral TH-positive cells survived in the Ad-GDNF group, compared to approximately 30% for the Ad-LacZ or PBS control group. Histochemical analysis of monoamine levels in the striatum demonstrated that the dopamine content was higher for the Ad-GDNF group than the control groups. Similarly, Ad-GDNF treated animals showed improved apomorphine-induced rotational behavior. The exogenous GDNF gene was efficiently expressed in the brain as detected by ELISA. This work demonstrates that intracerebral adeno-viral mediated GDNF gene transfer can protect dopaminergic neurons in vivo from 6-OHDA-induced injuries. The approach used in this study could potentially be used therapeutically in patients with PD and further work is required to explore this idea in depth.
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D018014:Gene Transfer Techniques; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents