QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (61) Citing Articles via Google Scholar Google Scholar Articles by Ho, A. Articles by Blum, M. Search for Related Content PubMed PubMed Citation Articles by Ho, A. Articles by Blum, M.

 Previous Article  |  Next Article 

The Journal of Neuroscience, August 1, 1998, 18(15):5614-5629

Induction of Interleukin-1 Associated with Compensatory Dopaminergic Sprouting in the Denervated Striatum of Young Mice: Model of Aging and Neurodegenerative Disease

Angela Ho and Mariann Blum

Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029

Young mice challenged with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which selectively destroys the substantia nigra dopaminergic neurons in the midbrain, exhibit spontaneous recovery of dopaminergic nerve terminals. However, such recovery becomes attenuated with age. Here we report that newly sprouted fibers originate from spared dopaminergic neurons in the ventral tegmental area. We found that interleukin-1 (IL-1), an immune response-generated cytokine that can enhance dopaminergic sprouting when exogenously applied, increased dramatically in the denervated striatum of young mice (2 months) compared with middle-aged mice (8 months) after MPTP treatment. Young mice displayed a maximal 500% induction of IL-1 synthesis that remained elevated for several weeks in the dorsal and ventral striatum, whereas middle-aged mice exhibited a modest 135% induction exclusively in the dorsal striatum for a week. IL-1 immunoreactivity was localized in GFAP-immunoreactive hypertrophied astrocytes and neurons within the denervated striatum of young mice. However, no induction of IL-1 mRNA was seen in the midbrain in either age group despite glial activation. Because we have reported that IL-1 can regulate astroglia-derived dopaminergic neurotrophic factors, it was surprising that no changes were observed in acidic and basic fibroblast growth factor or glial cell line-derived neurotrophic factor mRNA levels associated with MPTP-induced plasticity of dopaminergic neurons in the striatum of young mice. Interestingly, we found that dopaminergic neurons express IL-1 receptors, thus suggesting that IL-1 could directly act as a target-derived dopaminergic neurotrophic factor to initiate or enhance the sprouting of dopaminergic axonal terminals. These findings strongly suggest that IL-1 could play an important role in MPTP-induced plasticity of dopaminergic neurons.

Key words: IL-1; compensatory sprouting; dopaminergic neurons; growth factors; MPTP; Parkinson's disease; aging

---

Copyright © 1998 Society for Neuroscience  0270-6474/98/18155614-16$05.00/0

This article has been cited by other articles:

				M. Geraerts, O. Krylyshkina, Z. Debyser, and V. Baekelandt Concise Review: Therapeutic Strategies for Parkinson Disease Based on the Modulation of Adult Neurogenesis Stem Cells, February 1, 2007; 25(2): 263 - 270. [Abstract] [Full Text] [PDF]

				S. Chandra, F. Fornai, H.-B. Kwon, U. Yazdani, D. Atasoy, X. Liu, R. E. Hammer, G. Battaglia, D. C. German, P. E. Castillo, et al. Double-knockout mice for {alpha}- and {beta}-synucleins: Effect on synaptic functions PNAS, October 12, 2004; 101(41): 14966 - 14971. [Abstract] [Full Text] [PDF]

				C. L. Parish, D. I. Finkelstein, W. Tripanichkul, A. R. Satoskar, J. Drago, and M. K. Horne The Role of Interleukin-1, Interleukin-6, and Glia in Inducing Growth of Neuronal Terminal Arbors in Mice J. Neurosci., September 15, 2002; 22(18): 8034 - 8041. [Abstract] [Full Text] [PDF]

				C. L. Parish, D. I. Finkelstein, J. Drago, E. Borrelli, and M. K. Horne The Role of Dopamine Receptors in Regulating the Size of Axonal Arbors J. Neurosci., July 15, 2001; 21(14): 5147 - 5157. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help