Cellular neuroscienceImpaired nerve regeneration and enhanced neuroinflammatory response in mice lacking pituitary adenylyl cyclase activating peptide
Section snippets
Animals
PACAP deficient (knockout, KO) mice, were previously generated by targeted mutagenesis (Colwell et al., 2004). The gene targeting strategy removed sequences encoding PACAP and also PACAP-related peptide, a peptide of unknown biological significance. These mice were found by sensitive radioimmunoassay to not express PACAP in the brain or peripheral sites (Colwell et al., 2004). All mice used in these experiments were 2 to 4-month-old females, and were generated after backcrossing the mutation to
Motor neuron survival after axotomy in PACAP-deficient mice
PACAP has been shown to act as a neuronal survival factor on cultured cerebellar granule, sensory, autonomic and other types of neurons, and has been shown to promote neuron survival in various in vivo experimental CNS injury paradigms (reviewed in Waschek 2002, Atlasz et al 2007, Botia et al 2007). Thus, it was of considerable interest to determine if lack of endogenous PACAP results in impaired neuron survival after facial nerve axotomy. However, we found no difference between the PACAP KO
Discussion
An abundance of in vivo and in vitro data indicates that exogenous PACAP can act on developing or injured neurons to promote their survival (Vaudry et al 2000, Waschek 2002). Tissue cultures studies also indicate that PACAP can stimulate neurite outgrowth (Waschek, 2002), guide growth cones from immature neurons (Guirland et al., 2003) and regulate myelinogenesis (Lee et al., 2001), suggesting that PACAP might also act in the process of axon regeneration after injury. The generation of a PACAP
Acknowledgments
This work was supported by NIH grants HD06576 and HD04612, and grants from the Norman Cousins Center for Psychoneuroimmunology, and the Roman Reed Spinal Cord Injury Research Fund of California. We thank Dr. He-Jing Wang for help with statistical analyses of the data.
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