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

NEUROBIOLOGY OF DISEASE

卷:33

Article

Boger, Heather A.^1,2  Middaugh, Lawrence D.^1,2,3  Granholm, Ann-Charlotte^1,2  McGinty, Jacqueline F.^1,2,3 

[1] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA

[2] Med Univ S Carolina, Ctr Aging, Charleston, SC 29425 USA

[3] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA

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

DOI  :  10.1016/j.nbd.2008.11.013

来源: Elsevier

【 摘 要 】

inflammation. phospho-p38 MAPK activation, and a reduction in glial cell line-derived neurotrophic factor (GDNF) occur in Parkinson's disease. Mlicroglial 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 cur-rent 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. (C) 2008 Elsevier Inc. All rights reserved.

【 授权许可】

Free