@article {Kearns7111, author = {Cecilia M. Kearns and Wayne A. Cass and Kyle Smoot and Richard Kryscio and Don M. Gash}, title = {GDNF Protection against 6-OHDA: Time Dependence and Requirement for Protein Synthesis}, volume = {17}, number = {18}, pages = {7111--7118}, year = {1997}, doi = {10.1523/JNEUROSCI.17-18-07111.1997}, publisher = {Society for Neuroscience}, abstract = {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.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/17/18/7111}, eprint = {https://www.jneurosci.org/content/17/18/7111.full.pdf}, journal = {Journal of Neuroscience} }