Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Is Involved in Adult Mouse Hippocampal Neurogenesis After Stroke.

Abstract

In the subgranular zone (SGZ) of the hippocampus, neurogenesis persists throughout life and is upregulated following ischemia. Accumulating evidence suggests that enhanced neurogenesis stimulated by ischemic injury contributes to recovery after stroke. However, the mechanisms underlying the upregulation of neurogenesis are unclear. We have demonstrated that a neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), exerts a wide range of effects on neural stem cells (NSCs) during neural development. Here, we examined the effects of endogenous and exogenous PACAP in adult NSCs of the SGZ. Immunostaining showed expression of the PACAP receptor PAC1R in nestin-positive NSCs of adult naive mice. PACAP injection into the lateral ventricle increased bromodeoxyuridine (BrdU)-positive proliferative cells in the SGZ. These data suggest that PACAP promoted the proliferation of NSCs. In global ischemia model mice, the number of BrdU-positive cells was increased in wild-type mice but not in PACAP heterozygous knockout mice. The BrdU-positive cells that increased in number after ischemia were immunopositive for SOX2, a marker of NSCs, and differentiated into NeuN-positive mature neurons at 4 weeks after ischemia. These findings suggest that PACAP contributes to the proliferation of NSCs and may be associated with recovery after brain injury.

• Authors: Minako Matsumoto, Tomoya Nakamachi, Jun Watanabe, Koichi Sugiyama, Hirokazu Ohtaki, Norimitsu Murai, Shun Sasaki, Zhifang Xu, Hitoshi Hashimoto, Tamotsu Seki, Akira Miyazaki, Seiji Shioda
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 59 Issue 2 Pg. 270-9 (Jun 2016) ISSN: 1559-1166 [Electronic] United States
• PMID: 26910758 (Publication Type: Journal Article)

Chemical References

• Nestin
• Pituitary Adenylate Cyclase-Activating Polypeptide
• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
• SOXB1 Transcription Factors
• Sox2 protein, mouse

Topics

• Animals
• Cells, Cultured
• Heterozygote
• Hippocampus (metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Nestin (genetics, metabolism)
• Neural Stem Cells (cytology, drug effects, metabolism)
• Neurogenesis
• Pituitary Adenylate Cyclase-Activating Polypeptide (genetics, metabolism, pharmacology)
• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide (genetics, metabolism)
• SOXB1 Transcription Factors (genetics, metabolism)
• Stroke (metabolism, pathology)