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The Role of Galanin in Cerebellar Granule Cell Migration in the Early Postnatal Mouse during Normal Development and after Injury.

Authors
  • Komuro, Yutaro1
  • Galas, Ludovic2
  • Morozov, Yury M3
  • Fahrion, Jennifer K1
  • Raoult, Emilie2
  • Lebon, Alexis2
  • Tilot, Amanda K4
  • Kikuchi, Shin1
  • Ohno, Nobuhiko1, 5, 6
  • Vaudry, David2, 7
  • Rakic, Pasko3, 8
  • Komuro, Hitoshi9, 3
  • 1 Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195.
  • 2 Regional Platform for Cell Imaging of Normandy, INSERM, Université de Rouen Normandie, 76000 Rouen, France. , (France)
  • 3 Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510.
  • 4 Department of Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195.
  • 5 Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Aichi 444-8787, Japan. , (Japan)
  • 6 Department of Anatomy, Division of Histology and Cell Biology, School of Medicine, Jichi Medical University, Tochigi 329-0498, Japan. , (Japan)
  • 7 Neuropeptides, Neuronal Death and Cell Plasticity Team, Laboratory of Neuronal and Neuroendocrine Communication and Differentiation, INSERM U1239, Université de Rouen Normandie, 76000 Rouen, France. , (France)
  • 8 Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510.
  • 9 Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195 [email protected]
Type
Published Article
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Publication Date
Oct 20, 2021
Volume
41
Issue
42
Pages
8725–8741
Identifiers
DOI: 10.1523/JNEUROSCI.0900-15.2021
PMID: 34462307
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Galanin, one of the most inducible neuropeptides, is widely present in developing brains, and its expression is altered by pathologic events (e.g., epilepsy, ischemia, and axotomy). The roles of galanin in brain development under both normal and pathologic conditions have been hypothesized, but the question of how galanin is involved in fetal and early postnatal brain development remains largely unanswered. In this study, using granule cell migration in the cerebellum of early postnatal mice (both sexes) as a model system, we examined the role of galanin in neuronal cell migration during normal development and after brain injury. Here we show that, during normal development, endogenous galanin participates in accelerating granule cell migration via altering the Ca2+ and cAMP signaling pathways. Upon brain injury induced by the application of cold insults, galanin levels decrease at the lesion sites, but increase in the surroundings of lesion sites. Granule cells exhibit the following corresponding changes in migration: (1) slowing down migration at the lesion sites; and (2) accelerating migration in the surroundings of lesion sites. Experimental manipulations of galanin signaling reduce the lesion site-specific changes in granule cell migration, indicating that galanin plays a role in such deficits in neuronal cell migration. The present study suggests that manipulating galanin signaling may be a potential therapeutic target for acutely injured brains during development.SIGNIFICANCE STATEMENT Deficits in neuronal cell migration caused by brain injury result in abnormal development of cortical layers, but the underlying mechanisms remain to be determined. Here, we report that on brain injury, endogenous levels of galanin, a neuropeptide, are altered in a lesion site-specific manner, decreasing at the lesion sites but increasing in the surroundings of lesion sites. The changes in galanin levels positively correlate with the migration rate of immature neurons. Manipulations of galanin signaling ameliorate the effects of injury on neuronal migration and cortical layer development. These results shed a light on galanin as a potential therapeutic target for acutely injured brains during development. Copyright © 2021 the authors.

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