Age-related microglial activation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration in C57BL/6 mice.
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.
Sugama
Shuei
S
Harold L. Dorris Neurological Research Center, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. ssugama@scripps.edu
Yang
Lichuan
L
Cho
Byung Pil
BP
DeGiorgio
Lorraine A
LA
Lorenzl
Stefan
S
Albers
David S
DS
Beal
M Flint
MF
Volpe
Bruce T
BT
Joh
Tong H
TH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000375:Aging; D000818:Animals; D002452:Cell Count; D016923:Cell Death; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000201:enzymology / Q000378:metabolism*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D013378:Substantia Nigra / Q000201:enzymology / Q000378:metabolism*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine