Minocycline restores striatal tyrosine hydroxylase in GDNF heterozygous mice but not in methamphetamine-treated mice

Neurobiology of Disease

Ann-Charlotte Granholm¹  Lawrence D. Middaugh²  Jacqueline F. McGinty²  Heather A. Boger² 

[1] Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425, USA;Department of Neurosciences and Center on Aging, Medical University of South Carolina 173 Ashley Avenue BSB 403, Charleston, SC 29425, USA;

关键词: Dopamine;    Striatum;    Substantia nigra;    Neuroinflammation;    Neurotoxicity;    Neurotrophins;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.×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.

【 授权许可】

Unknown