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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 22, 2006, 26(12):3182-3191; doi:10.1523/JNEUROSCI.0156-06.2006

This Article Full Text Full Text (PDF) Supplemental data A correction has been published 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 (37) Citing Articles via Google Scholar Google Scholar Articles by Belmadani, A. Articles by Miller, R. J. Search for Related Content PubMed PubMed Citation Articles by Belmadani, A. Articles by Miller, R. J.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Chemokines Regulate the Migration of Neural Progenitors to Sites of Neuroinflammation

Abdelhak Belmadani, ^* Phuong B. Tran, ^* Dongjun Ren, and Richard J. Miller

Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611

Correspondence should be addressed to Prof. Richard J. Miller, Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, 303 East Chicago Avenue, Ward 8-296, Chicago, IL 60611. Email: r-miller10{at}northwestern.edu

Many studies have shown that transplanted or endogenous neural progenitor cells will migrate toward damaged areas of the brain. However, the mechanism underlying this effect is not clear. Here we report that, using hippocampal slice cultures, grafted neural progenitor cells (NPs) migrate toward areas of neuroinflammation and that chemokines are a major regulator of this process. Migration of NPs was observed after injecting an inflammatory stimulus into the area of the fimbria and transplanting enhanced green fluorescent protein (EGFP)-labeled NPs into the dentate gyrus of cultured hippocampal slices. Three to 7 d after transplantation, EGFP–NPs in control slices showed little tendency to migrate and had differentiated into neurons and glia. In contrast, in slices injected with inflammatory stimuli, EGFP–NPs migrated toward the site of the injection. NPs in these slices also survived less well. The inflammatory stimuli used were a combination of the cytokines tumor necrosis factor- and interferon-, the bacterial toxin lipopolysaccharide, the human immunodeficiency virus-1 coat protein glycoprotein 120, or a -amyloid-expressing adenovirus. We showed that these inflammatory stimuli increased the synthesis of numerous chemokines and cytokines by hippocampal slices. When EGFP–NPs from CC chemokine receptor CCR₂ knock-out mice were transplanted into slices, they exhibited little migration toward sites of inflammation. Similarly, wild-type EGFP–NPs exhibited little migration toward inflammatory sites when transplanted into slices prepared from monocyte chemoattractant protein-1 (MCP-1) knock-out mice. These data indicate that factors secreted by sites of neuroinflammation are attractive to neural progenitors and suggest that chemokines such as MCP-1 play an important role in this process.

Key words: CCR₂ receptors; MCP-1; migration; neural progenitors; neurogenesis; neuroinflammation; neural precursor

---

Received July 29, 2005; revised Feb. 5, 2006; accepted Feb. 7, 2006.

Correspondence should be addressed to Prof. Richard J. Miller, Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, 303 East Chicago Avenue, Ward 8-296, Chicago, IL 60611. Email: r-miller10{at}northwestern.edu

This article has been cited by other articles:

				H. Qin, S. A. Niyongere, S. J. Lee, B. J. Baker, and E. N. Benveniste Expression and Functional Significance of SOCS-1 and SOCS-3 in Astrocytes J. Immunol., September 1, 2008; 181(5): 3167 - 3176. [Abstract] [Full Text] [PDF]

				W. R. Kim, Y. Kim, B. Eun, O.-h. Park, H. Kim, K. Kim, C.-H. Park, S. Vinsant, R. W. Oppenheim, and W. Sun Impaired Migration in the Rostral Migratory Stream But Spared Olfactory Function after the Elimination of Programmed Cell Death in Bax Knock-Out Mice J. Neurosci., December 26, 2007; 27(52): 14392 - 14403. [Abstract] [Full Text] [PDF]

				F. Osakada, S. Ooto, T. Akagi, M. Mandai, A. Akaike, and M. Takahashi Wnt Signaling Promotes Regeneration in the Retina of Adult Mammals J. Neurosci., April 11, 2007; 27(15): 4210 - 4219. [Abstract] [Full Text] [PDF]

				T. Bliss, R. Guzman, M. Daadi, and G. K. Steinberg Cell Transplantation Therapy for Stroke Stroke, February 1, 2007; 38(2): 817 - 826. [Abstract] [Full Text] [PDF]

				C. Lauro, M. Catalano, F. Trettel, F. Mainiero, M. T. Ciotti, F. Eusebi, and C. Limatola The Chemokine CX3CL1 Reduces Migration and Increases Adhesion of Neurons with Mechanisms Dependent on the beta1 Integrin Subunit J. Immunol., December 1, 2006; 177(11): 7599 - 7606. [Abstract] [Full Text] [PDF]

				Y. Ziv, H. Avidan, S. Pluchino, G. Martino, and M. Schwartz Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury PNAS, August 29, 2006; 103(35): 13174 - 13179. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help