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Differential effects of glial cell line-derived neurotrophic factor (GDNF) in the striatum and substantia nigra of the aged Parkinsonian rat.
Gene Ther. 1999 Dec; 6(12):1936-51.GT

Abstract

Injection of an adenoviral (Ad) vector encoding human glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic (DA) neurons in the substantia nigra (SN) of young rats. As Parkinson's disease occurs primarily in aged populations, we examined whether chronic biosynthesis of GDNF, achieved by adenovirus-mediated delivery of a GDNF gene (AdGDNF), can protect DA neurons and improve DA-dependent behavioral function in aged (20 months) rats with progressive 6-OHDA lesions of the nigrostriatal projection. Furthermore, the differential effects of injecting AdGDNF either near DA cell bodies in the SN or at DA terminals in the striatum were compared. AdGDNF or control vector was injected unilaterally into either the striatum or SN. One week later, rats received a unilateral intrastriatal injection of 6-OHDA on the same side as the vector injection. AdGDNF injection into either the striatum or SN significantly reduced the loss of FG labelled DA neurons 5 weeks after lesion (P </= 0.05). However, only striatal injections of AdGDNF protected against the development of behavioral deficits characteristic of unilateral DA depletion. Striatal AdGDNF injections also reduced tyrosine hydroxylase fiber loss and increased amphetamine-induced striatal Fos expression. These results demonstrate that increased levels of striatal, but not nigral, GDNF biosynthesis prevents DA neuronal loss and protects DA terminals from 6-OHDA-induced damage, thereby maintaining DA function in the aged rat.

Authors+Show Affiliations

Department of Psychology, University of Texas, Austin, TX, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10637445

Citation

Connor, B, et al. "Differential Effects of Glial Cell Line-derived Neurotrophic Factor (GDNF) in the Striatum and Substantia Nigra of the Aged Parkinsonian Rat." Gene Therapy, vol. 6, no. 12, 1999, pp. 1936-51.
Connor B, Kozlowski DA, Schallert T, et al. Differential effects of glial cell line-derived neurotrophic factor (GDNF) in the striatum and substantia nigra of the aged Parkinsonian rat. Gene Ther. 1999;6(12):1936-51.
Connor, B., Kozlowski, D. A., Schallert, T., Tillerson, J. L., Davidson, B. L., & Bohn, M. C. (1999). Differential effects of glial cell line-derived neurotrophic factor (GDNF) in the striatum and substantia nigra of the aged Parkinsonian rat. Gene Therapy, 6(12), 1936-51.
Connor B, et al. Differential Effects of Glial Cell Line-derived Neurotrophic Factor (GDNF) in the Striatum and Substantia Nigra of the Aged Parkinsonian Rat. Gene Ther. 1999;6(12):1936-51. PubMed PMID: 10637445.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential effects of glial cell line-derived neurotrophic factor (GDNF) in the striatum and substantia nigra of the aged Parkinsonian rat. AU - Connor,B, AU - Kozlowski,D A, AU - Schallert,T, AU - Tillerson,J L, AU - Davidson,B L, AU - Bohn,M C, PY - 2000/1/19/pubmed PY - 2000/2/26/medline PY - 2000/1/19/entrez SP - 1936 EP - 51 JF - Gene therapy JO - Gene Ther VL - 6 IS - 12 N2 - Injection of an adenoviral (Ad) vector encoding human glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic (DA) neurons in the substantia nigra (SN) of young rats. As Parkinson's disease occurs primarily in aged populations, we examined whether chronic biosynthesis of GDNF, achieved by adenovirus-mediated delivery of a GDNF gene (AdGDNF), can protect DA neurons and improve DA-dependent behavioral function in aged (20 months) rats with progressive 6-OHDA lesions of the nigrostriatal projection. Furthermore, the differential effects of injecting AdGDNF either near DA cell bodies in the SN or at DA terminals in the striatum were compared. AdGDNF or control vector was injected unilaterally into either the striatum or SN. One week later, rats received a unilateral intrastriatal injection of 6-OHDA on the same side as the vector injection. AdGDNF injection into either the striatum or SN significantly reduced the loss of FG labelled DA neurons 5 weeks after lesion (P </= 0.05). However, only striatal injections of AdGDNF protected against the development of behavioral deficits characteristic of unilateral DA depletion. Striatal AdGDNF injections also reduced tyrosine hydroxylase fiber loss and increased amphetamine-induced striatal Fos expression. These results demonstrate that increased levels of striatal, but not nigral, GDNF biosynthesis prevents DA neuronal loss and protects DA terminals from 6-OHDA-induced damage, thereby maintaining DA function in the aged rat. SN - 0969-7128 UR - https://www.unboundmedicine.com/medline/citation/10637445/Differential_effects_of_glial_cell_line_derived_neurotrophic_factor__GDNF__in_the_striatum_and_substantia_nigra_of_the_aged_Parkinsonian_rat_ L2 - https://doi.org/10.1038/sj.gt.3301033 DB - PRIME DP - Unbound Medicine ER -