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

Abstract

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.

• Authors: Xianwen Chen, Weiguo Liu, Yang Guoyuan, Zhenguo Liu, Stuart Smith, Donald B Calne, Shengdi Chen
• Journal: Parkinsonism & related disorders (Parkinsonism Relat Disord) Vol. 10 Issue 1 Pg. 1-7 (Oct 2003) ISSN: 1353-8020 [Print] England
• PMID: 14499199 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GDNF protein, human
• Gdnf protein, rat
• Glial Cell Line-Derived Neurotrophic Factor
• Nerve Growth Factors
• Neuroprotective Agents

Topics

• Adenoviridae (genetics)
• Animals
• Behavior, Animal
• Disease Models, Animal
• Gene Expression Regulation (genetics)
• Gene Transfer Techniques
• Glial Cell Line-Derived Neurotrophic Factor
• Humans
• Injections, Intraventricular
• Male
• Mesencephalon (metabolism)
• Nerve Growth Factors (administration & dosage, biosynthesis, genetics)
• Neuroprotective Agents (administration & dosage)
• Parkinson Disease (genetics, physiopathology, therapy)
• Rats
• Rats, Sprague-Dawley