PACAP/PAC1 autocrine system promotes proliferation and astrogenesis in neural progenitor cells

Abstract

The Pituitary adenylate cyclase-activating peptide (PACAP) ligand/type 1 receptor (PAC1) system regulates neurogenesis and gliogenesis. It has been well established that the PACAP/PAC1 system induces differentiation of neural progenitor cells (NPCs) through the Gs-mediated cAMP-dependent signaling pathway. However, it is unknown whether this ligand/receptor system has a function in proliferation of NPCs. In this study, we identified that PACAP and PAC1 were highly expressed and co-localized in NPCs of mouse cortex at embryonic day 14.5 (E14.5) and found that the PACAP/PAC1 system potentiated growth factor-induced proliferation of mouse cortical NPCs at E14.5 via Gq-, but not Gs-, mediated PLC/IP3-dependent signaling pathway in an autocrine manner. Moreover, PAC1 activation induced elongation of cellular processes and a stellate morphology in astrocytes that had the bromodeoxyuridine (BrdU)-incorporating ability of NPCs. Consistent with this notion, we determined that the most BrdU positive NPCs differentiated to astrocytes through PAC1 signaling. These results suggest that the PACAP/PAC1 system may play a dual role in neural/glial progenitor cells not only differentiation but also proliferation in the cortical astrocyte lineage via Ca2+-dependent signaling pathways through PAC1.

Pituitary adenylate cyclase-activating polypeptide stimulates glial fibrillary acidic protein gene expression in cortical precursor cells by activating Ras and Rap1

“…It is known that PACAP acts on PAC1 receptors expressed in cortical cells, but it exerts different actions depending on their 13 developmental stage. Thus, before birth PACAP promotes neuronal differentiation from early neural precursors (Suh et al, 2001) and astrogliogenesis from late precursors (Nishimoto et al, 2007;Vallejo and Vallejo, 2002), whereas postanally, PACAP regulates the growth and differentiation of oligodendrocyte progenitors (Lee et al, 2001). Therefore the signaling mechanisms on which PACAP acts during cortical development appear to differ in different cell lineages and to be developmentally regulated.…”

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…PACAP has been shown to promote differentiation of embryonic stem cells into neurons and differentiation of neural stem cells into astrocytes (Vallejo and Vallejo, 2002;Cazillis et al, 2004;Ohno et al, 2005;Chafai et al, 2006;Hirose et al, 2006;Watanabe et al, 2006;Nishimoto et al, 2007). In cells that differentiate into neurons, expression of PAC1-R is increased, whereas the level of expression decreases in cells with a glial phenotype .…”

A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects

“…26 After chitin beads (NEB) affinity chromatography purification was carried out for the cell lysate, the preparation, purity assay and identification were performed by reverse-phase high-performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry methods as previously described. 26,27 At room temperature, 100 μL chitosan (CTS, 0.8 mg/mL) was added to 1 mL of sodium selenite solution (5 mM) and mixed well by stirring, while 1 mL ascorbic acid solution (Vitamin C, 20 mM) was added to the solution. After it was allowed to stand for 30 min at 4°C, the mixture was dialyzed overnight (8 h) at 4°C, and thus, chitosan-modified SeNPs (SC) were obtained.…”