Minocycline restores striatal tyrosine hydroxylase in GDNF heterozygous mice but not in methamphetamine-treated mice.
Inflammation, phospho-p38 MAPK activation, and a reduction in glial cell line-derived neurotrophic factor (GDNF) occur in Parkinson's disease. Microglial activation in the substantia nigra and a tyrosine hydroxylase deficit in the striatum of 3-month-old GDNF heterozygous (GDNF(+/-)) mice were previously reported and both were exacerbated by a toxic methamphetamine binge. The current study assessed the effects of minocycline on these methamphetamine-induced effects. Minocycline (45 mg/kg, i.p.x 14 days post-methamphetamine or saline injections) reduced microglial activation and phospho-p38 MAPK in the substantia nigra of saline-treated GDNF(+/-) mice and in methamphetamine-treated wildtype and GDNF(+/-) mice. Although minocycline increased tyrosine hydroxylase-immunoreactivity in GDNF(+/-) mice, it did not attenuate the methamphetamine-induced reduction of tyrosine hydroxylase. The results suggest that neuroinflammation is deleterious to the dopamine system of GDNF(+/-) mice but is not the primary cause of methamphetamine-induced damage to the dopamine system in either GDNF(+/-) or wildtype mice.
Boger
Heather A
HA
Department of Neurosciences and Center on Aging, Medical University of South Carolina 173 Ashley Avenue BSB 403, Charleston, SC 29425, USA.
Middaugh
Lawrence D
LD
Granholm
Ann-Charlotte
AC
McGinty
Jacqueline F
JF
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics*; D006579:Heterozygote; D007150:Immunohistochemistry; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D008911:Minocycline / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010784:Photomicrography; D013378:Substantia Nigra / Q000187:drug effects* / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D051100:Glial Cell Line-Derived Neurotrophic Factor; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D048051:p38 Mitogen-Activated Protein Kinases; D008911:Minocycline