Multiple Actions of Pituitary Adenylyl Cyclase Activating Peptide in Nervous System Development and Regeneration

Pituitary adenylyl cyclase activating peptide (PACAP) is widely expressed in the embryonic brain at the onset of neurogenesis, and is strongly upregulated in several models of nerve injury. Moreover, high-affinity PACAP receptors are expressed in proliferative zones in the embryonic and postnatal nervous system suggesting that PACAP regulates the development of both neuronal and glial precursors. Tissue culture studies indicate that PACAP exerts a variety of growth factor-like actions that depend on the origin of the cell population and developmental stage. These effects include regulation of proliferation, survival, maturation, neurite outgrowth, and expression of trophic factors, cytokines and trk receptors. The presence of other growth factors can also markedly affect these actions of PACAP, for example, reversing PACAP's effect from proliferative to antiproliferative. In vivo models now provide additional evidence that PACAP acts in neural development and regeneration.