Long-term effect of MPTP in the mouse brain in relation to aging: neurochemical and immunocytochemical analysis

Isao Date, David L. Felten, Suzanne Y. Felten

研究成果査読

117 被引用数 (Scopus)

抄録

The long-term effect of the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central monoaminergic neurons in young (2-3 months) and aging (12 months) C57BL/6 mice has been studied using neurochemical and immunocytochemical techniques. MPTP treatment (4 × 20 mg/kg i.p. given 12 h apart) resulted in significant depletion of dopamine (DA) concentration in the striatum, substantia nigra, nucleus accumbens, and olfactory tubercle 1 week after treatment in both young and aging mice. Although a decreased DA concentration in the ventral tegmental area was not seen in young mice, aging mice did show a significant decrease. The extent of decrease of DA concentration was greater in aging mice than in young mice in all areas investigated except in dorsal striatum. The long-term effect of MPTP on DA neurons in young mice included considerable recovery of DA concentration in both nigrostriatal and mesolimbic DA systems following the initial profound depletion; such recovery was minimal in aging mice, even 3 months after MPTP treatment. In young mice treated with MPTP, no significant change of norepinephrine (NE) or serotonin (5-HT) concentration was observed in any area investigated while a significant decrease of NE and 5-HT concentration was seen in several brain areas investigated in aging mice. Immunocytochemical analysis revealed that the MPTP injection resulted in marked disappearance of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in striatum of both young and aging mice 1 week following treatment. Partial recovery of TH-IR fibers was seen 5 weeks or 3 months after MPTP treatment in young mice, while no such apparent recovery was seen in aging mice. Aging mice also showed significant decrease in the number of TH-positive cell bodies in the substantia nigra and ventral tegmental area through all periods investigated, while such a significant decrease was only seen in the substantia nigra of young mice 1 week after treatment. We conclude that aging mice are more sensitive to MPTP and show more widespread damage to the monoaminergic systems than young mice, suggesting that MPTP-treated aging mice provide a more useful model for studying anatomical and neurochemical characteristics of Parkinson's disease than young mice.

本文言語English
ページ(範囲)266-276
ページ数11
ジャーナルBrain Research
519
1-2
DOI
出版ステータスPublished - 6月 11 1990
外部発表はい

ASJC Scopus subject areas

  • 神経科学一般
  • 分子生物学
  • 臨床神経学
  • 発生生物学

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