Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Stimulates Proliferation of Reactive Astrocytes In Vitro

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide originally isolated from ovine hypothalamus. Recently, we have shown that the PACAP receptor (PAC1-R) is expressed in reactive astrocytes following an in vivo stub wound brain injury. However, the functional role of PACAP has not yet been clarified. In order to investigate the effect of PACAP on the proliferation of reactive astrocytes, a scratch wound paradigm was applied to astrocytic monolayers. Following injury, there was an increase in PAC1-R and glial fibrillary acidic protein (GFAP) immunoreactivity in the astrocytes surrounding the scratch line. PACAP at concentrations of 10(-15) to 10(-7) M was applied immediately after scratching, and the proliferating astrocytes were visualized by multiple immunofluorescence labeling. The percentage of cells that colabeled for Ki67 (a marker of proliferating cells) and GFAP increased in the 10(-11)- and 10(-13)-M PACAP-treated groups. The proliferating astrocytes induced by PACAP treatment mainly occurred in the proximal wound area where many reactive astrocytes were observed. Pretreatment with the PACAP receptor antagonist PACAP6-38 significantly suppressed the PACAP-induced effects. These results strongly suggest that PACAP plays an important role in the proliferation of reactive astrocytes following nerve injury.

Pituitary adenylate cyclase-activating polypeptide protects astroglial cells against oxidative stress-induced apoptosis

“…2004; Stumm et al. 2007) and in reactive astrocytes in culture (Nakamachi et al. 2010), highlighting the importance of astroglial cells in the neuroprotective activity of PACAP.…”

The Protective Effects of Endogenous PACAP in Oxygen-Induced Retinopathy

“…Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid pleiotropic peptide known to act as a neurotransmitter, neuromodulator, and neurotrophic factor (Nakamachi et al 2011;Ciranna and Costa 2019;Johnson et al 2020;Gargiulo et al 2020). PACAP consistently exerts protective effects in the nervous system and peripheral organs by mediating various physiological processes (Martinez-Rojas et al 2021;Nonaka et al 2020;Toth et al 2020).…”

The Protective Effects of Endogenous PACAP in Oxygen-induced Retinopathy 

“…Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid pleiotropic peptide known to act as a neurotransmitter, neuromodulator and neurotrophic factor (Nakamachi et al 2011;Johnson et al 2020;Gargiulo et al 2020;Ciranna and Costa 2019). PACAP consistently exerts protective effects in the nervous system and in peripheral organs (Martinez-Rojas et al 2020; Nonaka et al 2020;Toth et al 2020).…”