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Balanced effect of PACAP and FasL on granule cell death during cerebellar development: a morphological, functional and behavioural characterization
Author(s) -
Allais Aurélie,
Burel Delphine,
Roy Vincent,
Arthaud Sébastien,
Galas Ludovic,
Isaac Emma Rachel,
Desfeux Arnaud,
Parent Bénédicte,
Fournier Alain,
Chapillon Pierre,
Sherwood Nancy McKeown,
Vaudry Hubert,
Gonzalez Bruno José
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06555.x
Subject(s) - fas ligand , granule cell , apoptosis , biology , microbiology and biotechnology , cerebellum , ex vivo , caspase 3 , medicine , endocrinology , programmed cell death , chemistry , central nervous system , in vitro , biochemistry , dentate gyrus
J. Neurochem. (2010) 113 , 329–340. Abstract It is now established that the development of the CNS requires equilibrium between cell survival and apoptosis. Pituitary adenylate cyclase‐activating polypeptide (PACAP) exerts a powerful protective effect on cerebellar granule cells by inhibiting the caspase 3. In contrast, Fas ligand (FasL) plays an essential role during ontogenesis in eliminating supernumerary neurons by apoptosis. To determine if PACAP and FasL interact during cerebellar development, we characterized the effects of these factors on cerebellar morphogenesis and caspase 3 activity in PACAP+/+ and PACAP−/− mice. First, we demonstrated in vivo that PACAP is able to reverse the diminution of internal granule cell layer thickness induced by FasL in PACAP+/+ and PACAP−/− mice. Second, ex vivo and immunohistochemical studies revealed that interaction between FasL and PACAP occurs through the caspase 3 activity. Third, behavioural study showed a significant difference for the PACAP + FasL group in the righting reflex test at P8 which does not persist at P60. Finally, a time course study revealed that the pro‐apoptotic effect of FasL characterized at P8 was followed by a progressive compensatory mechanism in caspase 3 activity and bromodeoxyuridine incorporation. These data suggest that PACAP and FasL interact during cerebellar development to control apoptosis of granule cells and may affect some motor cerebellar functions.