RT Journal Article
SR Electronic
T1 GDNF Protection against 6-OHDA: Time Dependence and Requirement for Protein Synthesis
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7111
OP 7118
DO 10.1523/JNEUROSCI.17-18-07111.1997
VO 17
IS 18
A1 Kearns, Cecilia M.
A1 Cass, Wayne A.
A1 Smoot, Kyle
A1 Kryscio, Richard
A1 Gash, Don M.
YR 1997
UL http://www.jneurosci.org/content/17/18/7111.abstract
AB 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.