Protective effects of the intracerebral transfer of the adenoviral-mediated GDNF gene in a rat model of Parkinson's disease / 中华老年医学杂志

ABSTRACT

Objective To study the neuroprotective effects of adeno viral mediated glial cell line derived neurotrophic factor(GDNF) gene transfer in the treatment of Parkinson's disease. Methods Thirty five SD rats were divided into 3 groups which received perinigral injections of recombinant adenovirus encoding GDNF (Ad GDNF)/ LacZ(Ad LacZ) and PBS, respectively. One week later, intrastriatal injection of 6 hydroxydopamine (6 OHDA) was made to induce progressive degeneration of dopaminergic neurons. The neuroprotective effects of Ad GDNF were evaluated by apomorphine induced rotational behavior, immunohistochemical assay of the tyrosine hydroxylase(TH) positive neurons in the midbrain and measurement of monoamine level in the striatum. RT PCR and ELISA were performed to check the expression of the exogenous GDNF gene in the brain. Results Ad GDNF treated rats showed improved motor functions, better survival of TH positive cells in the lesioned substantia nigra (70% vs 30%) and higher DA levels in the lesioned striatum. The exogenous GDNF gene was efficiently expressed in the midbrain. GDNF protein level in the injection site reached 1 ng/10 mg wet tissue 5 weeks after the adenoviral vector delivery, being 16 20 times of that of the Ad LacZ delivery or PBS treated groups. Conclusions Adeno viral mediated GDNF gene intracerebral transfer significantly protected the dopaminergic neurons of nigrostriatal system from 6 OHDA induced injury and is valuable in the treatment of Parkinson's disease.