Protective effects of intracerebral adenoviral-mediated GDNF gene transfer in a rat model of Parkinson's disease

• Published in: Parkinsonism & related disorders 2003-10, Vol.10 (1), p.1-7
• Main Authors: Chen, Xianwen, Liu, Weiguo, Guoyuan, Yang, Liu, Zhenguo, Smith, Stuart, Calne, Donald B, Chen, Shengdi
• Format: Article
• Language: English
• Subjects: 6-Hydroxydopamine; Adeno-virus; Adenoviridae - genetics; Animals; Behavior, Animal; Disease Models, Animal; Dopamine neuron; Gene Expression Regulation - genetics; Gene therapy; Gene Transfer Techniques; Glial Cell Line-Derived Neurotrophic Factor; Humans; Injections, Intraventricular; Male; Mesencephalon - metabolism; Nerve Growth Factors - administration & dosage; Nerve Growth Factors - biosynthesis; Nerve Growth Factors - genetics; Neuroprotective Agents - administration & dosage; Parkinson Disease - genetics; Parkinson Disease - physiopathology; Parkinson Disease - therapy; Parkinson's disease; Rats; Rats, Sprague-Dawley
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/S1353-8020(03)00097-X

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.