title: Epac2 contributes to PACAP-induced astrocytic differentiation through calcium ion influx in neural precursor cells.
abstract: Astrocytes play a critical role in normal brain functions and maintaining the brain microenvironment, and defects in astrocytogenesis during neurodevelopment could give rise to severe mental illness and psychiatric disorders. During neuro-embryogenesis, astrocytogenesis involves astrocytic differentiation of neural precursor cells (NPCs) induced by signals from ciliary neurotrophic factor (CNTF) or pituitary adenylate cyclase-activating peptide (PACAP). However, in contrast to the CNTF signaling pathway, the exact mechanism underlying astrocytic differentiation induced by PACAP is unknown. In the present study, we aimed to verify a signaling pathway specific to PACAP-induced astrocytogenesis, using exchange protein directly activated by cAMP2 (Epac2)-knockout mice. We found that PACAP could trigger astrocytic differentiation of NPCs via Epac2 activation and an increase in the intracellular calcium concentration via a calcium ion influx. Taken together, we concluded that astrocytogenesis stimulated by PACAP occurs through a novel signaling pathway independent from CNTF-JAK/STAT signaling, that is the well-known pathway of astrocytogenesis. [BMB Reports 2016; 49(2): 128-133].
authors.affiliation: Department of Anatomy, Brain Science & Engineering Institute, Kyungpook National University Graduate School of Medicine, Daegu 41944, Korea.
authors.forename: Hyunhyo
authors.initials: H
authors.lastname: Seo
authors.affiliation: Department of Anatomy, Brain Science & Engineering Institute, Kyungpook National University Graduate School of Medicine, Daegu 41944, Korea.
authors.forename: Kyungmin
authors.initials: K
authors.lastname: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D007477:Ions; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005904:Glial Fibrillary Acidic Protein; D020662:Guanine Nucleotide Exchange Factors; D007477:Ions; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C486707:Rapgef4 protein, mouse; D002118:Calcium