QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (67) Citing Articles via Google Scholar Google Scholar Articles by Kearns, C. M. Articles by Gash, D. M. Search for Related Content PubMed PubMed Citation Articles by Kearns, C. M. Articles by Gash, D. M.

 Previous Article  |  Next Article 

Volume 17, Number 18, Issue of September 15, 1997 pp. 7111-7118
Copyright ©1997 Society for Neuroscience

GDNF Protection against 6-OHDA: Time Dependence and Requirement for Protein Synthesis

Received May 12, 1997; revised June 24, 1997; accepted June 30, 1997.

Cecilia M. Kearns¹, Wayne A. Cass¹, Kyle Smoot¹, Richard Kryscio², and Don M. Gash¹

¹ Department of Anatomy and Neurobiology, University of Kentucky Medical Center, Lexington, Kentucky 40536, and ² Department of Biostatistics, University of Kentucky Medical Center, Lexington, Kentucky 40536

Glial cell line-derived neurotrophic factor (GDNF) injected intranigrally protects midbrain dopamine neurons against 6-hydroxydopamine (6-OHDA) toxicity. The timing between GDNF administration and exposure to 6-OHDA is critical in achieving optimal protection. When injected 6 hr before an intranigral injection of 6-OHDA, GDNF provides complete protection as measured by the number of surviving neurons in the substantia nigra of adult rats. The surviving neuronal population decreases by ~50% with 12 and 24 hr separating GDNF and 6-OHDA administrations. In controls with 6-OHDA lesions, there is <10% survival of nigral dopamine neurons. No significant increase in survival is seen with either concurrent injections of GDNF and 6-OHDA or 1 hr GDNF pretreatment. Based on HPLC measurements, striatal and midbrain dopamine levels are at least twofold higher on the lesioned side in animals receiving GDNF 6 hr before a 6-OHDA lesion compared with vehicle recipients. Protein synthesis is necessary for GDNF-induced neuroprotective effects because cycloheximide pretreatment that inhibits protein synthesis also blocks neuroprotection.

Key words: GDNF; 6-OHDA; neuroprotection; substantia nigra; dopamine neurons; cycloheximide

This article has been cited by other articles:

				M. H. Voutilainen, S. Back, E. Porsti, L. Toppinen, L. Lindgren, P. Lindholm, J. Peranen, M. Saarma, and R. K. Tuominen Mesencephalic Astrocyte-Derived Neurotrophic Factor Is Neurorestorative in Rat Model of Parkinson's Disease J. Neurosci., July 29, 2009; 29(30): 9651 - 9659. [Abstract] [Full Text] [PDF]

				B. Georgievska, D. Kirik, and A. Bjorklund Overexpression of Glial Cell Line-Derived Neurotrophic Factor Using a Lentiviral Vector Induces Time- and Dose-Dependent Downregulation of Tyrosine Hydroxylase in the Intact Nigrostriatal Dopamine System J. Neurosci., July 21, 2004; 24(29): 6437 - 6445. [Abstract] [Full Text] [PDF]

				N. Kobori, J. C. Waymire, J. W. Haycock, G. L. Clifton, and P. K. Dash Enhancement of Tyrosine Hydroxylase Phosphorylation and Activity by Glial Cell Line-derived Neurotrophic Factor J. Biol. Chem., January 16, 2004; 279(3): 2182 - 2191. [Abstract] [Full Text] [PDF]

				D. Kirik, C. Rosenblad, A. Bjorklund, and R. J. Mandel Long-Term rAAV-Mediated Gene Transfer of GDNF in the Rat Parkinson's Model: Intrastriatal But Not Intranigral Transduction Promotes Functional Regeneration in the Lesioned Nigrostriatal System J. Neurosci., June 15, 2000; 20(12): 4686 - 4700. [Abstract] [Full Text] [PDF]

				E. D. Clarkson, J. Edwards-Prasad, C. R. Freed, and K. N. Prasad Immortalized Dopamine Neurons: A Model to Study Neurotoxicity and Neuroprotection Experimental Biology and Medicine, November 1, 1999; 222(2): 157 - 163. [Abstract] [Full Text]

				W. A. Cass and M. W. Manning GDNF Protection against 6-OHDA-Induced Reductions in Potassium-Evoked Overflow of Striatal Dopamine J. Neurosci., February 15, 1999; 19(4): 1416 - 1423. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help