Activated microglia affect the nigro-striatal dopamine neurons differently in neonatal and aged mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Microglia play an important role in the inflammatory process that occurs in Parkinson's disease (PD). Activated microglia produce cytokines and neurotrophins and may have neurotoxic or neurotrophic effects. Because microglia are most proliferative and easily activated during the neonatal period, we examined the effects of neonatal microglia activated with lipopolysaccharide (LPS) on the nigro-striatal dopamine neurons in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), in comparison with activated microglia from the aged mice. By MPTP administration to neonatal mice, the number of dopamine neurons in the substantia nigra (SN) was decreased significantly, whereas that in the mice treated with LPS and MPTP was recovered to normal, along with significant microglial activation. Tyrosine hydroxylase (TH) activity, the levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), and the levels of pro-inflammatory cytokines IL-1beta and IL-6 in the midbrain were elevated in the neonates treated with LPS and MPTP. On the contrary, although the number of dopamine neurons in the 60-week-old mice treated with MPTP was also decreased significantly, the microglial activation by LPS treatment caused a further decrease in their number. These results suggest that the activated microglia in neonatal mice are different from those in aged mice, with the former having neurotrophic potential toward the dopamine neurons in the SN, in contrast to the neurotoxic effect of the latter.
Sawada
Hirohide
H
School of Medicine, Fujita Health University, Toyoake, Japan.
Hishida
Ryohei
R
Hirata
Yoko
Y
Ono
Kenji
K
Suzuki
Hiromi
H
Muramatsu
Shin-ichi
S
Nakano
Imaharu
I
Nagatsu
Toshiharu
T
Sawada
Makoto
M
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine