1. Granule Cell Survival is Deficient in PAC1−/− Mutant Cerebellum
- Author
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Liana I. Tascau, Philippe Brabet, Anthony Falluel-Morel, Katie Sokolowski, Emanuel DiCicco-Bloom, Hamel, Christian, Department of Neuroscience and Cell Biology, Rutgers Biomedical and Health Sciences, Rutgers University System (Rutgers)-Rutgers University System (Rutgers), Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pediatrics, and Rutgers, The State University of New Jersey [New Brunswick] (RU)
- Subjects
endocrine system ,medicine.medical_specialty ,Cerebellum ,Cell Survival ,Endogeny ,Biology ,Mice ,Cellular and Molecular Neuroscience ,Internal medicine ,medicine ,Animals ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Receptor ,Mice, Knockout ,Neurons ,DNA synthesis ,Caspase 3 ,Neurogenesis ,Wild type ,DNA ,General Medicine ,Granule cell ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,Apoptosis ,Pituitary Adenylate Cyclase-Activating Polypeptide ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,hormones, hormone substitutes, and hormone antagonists ,Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I - Abstract
International audience; 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.
- Published
- 2008