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Granule Cell Survival is Deficient in PAC1−/− Mutant Cerebellum

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Abstract

PACAP exerts neuroprotective effects during development, especially in the cerebellum where PAC1 receptor and ligand are both expressed. However, while previous studies using PACAP injections in postnatal animals defined trophic effects of exogenous peptide, the role of endogenous PACAP remains unexplored. Here, we used PAC1−/− mice to investigate the role of PACAP receptor signaling in postnatal day 7 cerebellum. There was no difference in DNA synthesis in the cerebellar EGL of PAC1−/− compared to wild type animals, assessed using thymidine incorporation and BrdU immunohistochemistry. In contrast, we found that a significant proportion of newly generated neurons were eliminated before they successfully differentiated in the granule cell layer. In aggregate, these results suggest that endogenous PACAP plays an important role in cell survival during cerebellar development, through the activation of the PAC1 receptor.

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Abbreviations

BrdU:

bromodeoxyuridine

EGL:

external germinal layer

IGL:

internal granule cell layer

MOL:

molecular layer

PACAP:

Pituitary adenylate cyclase-activating polypeptide

PAC1:

PACAP-specific receptor 1

PAC1-/- :

PAC1-knockout mouse

PBS:

phosphate buffer saline

PFA:

paraformaldehyde

TCA:

trichloroacetic acid

Triton X100:

4-(1,1,3,3-Tetramethylbutyl)phenyl-polyethylene glycol

[3H]-Thy:

[3H]-thymidine

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Acknowledgements

This work was supported by NIH NS 32401. Anthony Falluel-Morel was a recipient of a Fellowship from La Fondation pour la Recherche Médicale (FRM-SPE20051105).

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Authors and Affiliations

  1. Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Room RWJSPH 362, Piscataway, NJ, 08854, USA

    Anthony Falluel-Morel, Liana I. Tascau, Katie Sokolowski & Emanuel DiCicco-Bloom

  2. INSERM U583, Montpellier, 34094, France

    Philippe Brabet

  3. Department of Pediatrics, The Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Emanuel DiCicco-Bloom

Authors
  1. Anthony Falluel-Morel
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  2. Liana I. Tascau
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  3. Katie Sokolowski
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  4. Philippe Brabet
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  5. Emanuel DiCicco-Bloom
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Correspondence to Emanuel DiCicco-Bloom.

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Falluel-Morel, A., Tascau, L.I., Sokolowski, K. et al. Granule Cell Survival is Deficient in PAC1−/− Mutant Cerebellum. J Mol Neurosci 36, 38–44 (2008). https://doi.org/10.1007/s12031-008-9066-6

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  • DOI: https://doi.org/10.1007/s12031-008-9066-6

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