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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 5, 2006, 26(27):7272-7280; doi:10.1523/JNEUROSCI.0837-06.2006

This Article Full Text Full Text (PDF) Supplemental data 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 Related articles in J. Neurosci. 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 (14) Citing Articles via Google Scholar Google Scholar Articles by Van Kampen, J. M. Articles by Eckman, C. B. Search for Related Content PubMed PubMed Citation Articles by Van Kampen, J. M. Articles by Eckman, C. B.

 Previous Article  |  Next Article 

Neurobiology of Disease
Dopamine D₃ Receptor Agonist Delivery to a Model of Parkinson's Disease Restores the Nigrostriatal Pathway and Improves Locomotor Behavior

Jackalina M. Van Kampen and Christopher B. Eckman

Departments of Pharmacology and Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224

Correspondence should be addressed to Dr. Christopher B. Eckman, Mayo Clinic College of Medicine, Birdsall Building Room 327, 4500 San Pablo Road, Jacksonville, FL 32224. Email: Eckman{at}mayo.edu

The presence of endogenous stem cell populations in the adult mammalian CNS suggests an innate potential for regeneration and represents a potential resource for neuroregenerative therapy aimed at the treatment of neurodegenerative disorders, such as Parkinson's disease. However, it is first necessary to examine the microenvironmental signals required to activate these innate reparative mechanisms. The small molecule neurotransmitter dopamine has been shown to regulate cell cycle in developing and adult brain, and the D₃ receptor is known to play an important role in dopaminergic development. Pharmacological activation of the dopamine D₃ receptor has been shown to trigger neurogenesis in the substantia nigra of the adult rat brain. Here, we examined the cell proliferative, neurogenic, and behavioral effects of the dopamine D₃ receptor agonist 7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin) in a 6-hydroxydopamine model of Parkinson's disease. Consistent with previous findings, we observed a significant induction of cell proliferation in the substantia nigra pars compacta (SN_C) with a time-dependent adoption of a neuronal dopaminergic phenotype in many of these cells. Indices of nigrostriatal integrity were also affected. Dopaminergic cell counts in the lesioned SN_C recovered substantially in a time-dependent manner. Similarly, retrograde tracing revealed a restoration of striatal innervation from these cells, with evidence for projections arising from newly generated cells. Finally, we observed a substantial and persistent recovery of locomotor function in these animals. The results of these studies will further our understanding of the environmental signals regulating neurogenesis in the adult brain and could have significant implications for the design of novel treatment strategies for Parkinson's disease.

Key words: Parkinson's disease; dopamine D₃ receptor; substantia nigra; neurogenesis; proliferation; rat

---

Received Feb. 23, 2006; revised April 17, 2006; accepted May 31, 2006.

Correspondence should be addressed to Dr. Christopher B. Eckman, Mayo Clinic College of Medicine, Birdsall Building Room 327, 4500 San Pablo Road, Jacksonville, FL 32224. Email: Eckman{at}mayo.edu

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2006 26: i. [Full Text]  

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]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help