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Brain Res. 2003 Feb 28;964(2):288-94.

Age-related microglial activation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration in C57BL/6 mice.

Author information

1
Harold L. Dorris Neurological Research Center, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. ssugama@scripps.edu

Abstract

Microglial activation was investigated in the brains of young (3 months old) and older (9-12 months old) mice following administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Tyrosine hydroxylase (TH)-positive neuronal loss differed significantly between young and older mice. Importantly, the two groups clearly demonstrated a distinct microglial activation pattern. In young mice which showed TH neuronal loss at 1 day (33.4%), 3 days (45.1%), 7 days (47.1%) and 14 days (46.9%), microglial activation was first observed at 1 day, with lesser activation at 3 days and none shown later than 7 days. In contrast, in older mice which showed TH neuronal loss at 1 day (49.6%), 3 days (56.1%), 7 days (71.7%) and 14 days (72.1%), microglial activation occurred at 1 day, further intensified at 3-7 days, and was largely abated by 14 days. The double immunohistochemistry further demonstrated that the activated microglia surrounded dopaminergic neurons in older mice at 7 days, which was sharply in contrast to the young mice which were devoid of massive microglial activation in the SN later than 3 days after MPTP treatment. The present study suggests that age-related microglial activation in the SN may be relevant to the higher susceptibility to MPTP neurotoxicity in older mice.

PMID:
12576189
DOI:
10.1016/s0006-8993(02)04085-4
[Indexed for MEDLINE]

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