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Long-term effect of MPTP in the mouse brain in relation to aging: neurochemical and immunocytochemical analysis
Open accessAbstract
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 x 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.
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Cited by
Blum, D., Torch, S., Lambeng, N., Nissou, M.-F., Benabid, A.-L., Sadoul, R., & Verna, J.-M. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(01)00003-x · Cited by 1,246
Gerlach, M., & Riederer, P. (1996) · Journal of Neural Transmission · doi:10.1007/bf01291788 · Cited by 498
Beal, M. F., Matthews, R. T., Tieleman, A., & Shults, C. W. (1998) · Brain Research · doi:10.1016/s0006-8993(97)01192-x · Cited by 256
Capucciati, A., Zucca, F. A., Monzani, E., Zecca, L., Casella, L., & Hofer, T. (2021) · Antioxidants · doi:10.3390/antiox10060824 · Cited by 36
The role of nitric oxide on visual-evoked potentials in MPTP-induced Parkinsonism in mice
Aras, S., Tanriover, G., Aslan, M., Yargicoglu, P., & Agar, A. (2014) · Neurochemistry International · doi:10.1016/j.neuint.2014.04.014 · Cited by 30
Metadata
- Authors
- Date, I., Felten, D. L., & Felten, S. Y.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1990-06
- Volume
- 519
- Issue
- 1-2
- Pages
- 266-276
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2006306666
- Cited by
- 158
- References
- 0
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Date, I., Felten, D. L., & Felten, S. Y. (1990). Long-term effect of MPTP in the mouse brain in relation to aging: neurochemical and immunocytochemical analysis. Brain Research. https://doi.org/10.1016/0006-8993(90)90088-s
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