Suppression of Astrocyte Lineage in Adult Hippocampal Progenitor Cells Expressing Hippocampal Cholinergic Neurostimulating Peptide Precursor in an in Vivo Ischemic Model

• Published in: Cell transplantation Vol. 21; no. 10; pp. 2159 - 2169
• Main Authors: Toyoda, Takanari, Matsukawa, Noriyuki, Sagisaka, Takafumi, Uematsu, Norihiko, Kanamori, Tetsuko, Kato, Daisuke, Mizuno, Masayuki, Wake, Hiroaki, Hida, Hideki, Borlongan, Cesario V., Ojika, Kosei
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.10.2012; SAGE Publishing
• Subjects: Animals; Astrocytes - cytology; Astrocytes - metabolism; Brain Ischemia - metabolism; Brain Ischemia - pathology; Cell Differentiation - physiology; Cell Growth Processes - physiology; Cell Lineage; Disease Models, Animal; Female; Immunohistochemistry; Male; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Phosphatidylethanolamine Binding Protein - biosynthesis; Rats; Rats, Sprague-Dawley; Neural differentiation; Hypoxic–ischemic model; Hippocampal cholinergic neurostimulating peptide precursor protein; Adult rat hippocampal progenitor cell
• ISSN: 0963-6897; 1555-3892
• DOI: 10.3727/096368911X627543

Hippocampal cholinergic neurostimulating peptide (HCNP) is known to promote differentiation of septohippocampal cholinergic neurons. The HCNP precursor protein (HCNP-pp) may play several roles, for example, as an ATP-binding protein, a Raf kinase inhibitor protein, and a phosphatidylethanolamine-binding protein, as well as a precursor for HCNP. This study therefore aimed to elucidate the involvement of HCNP-pp in specific neural lineages after stroke using a hypoxic–ischemic (HI) rat model of brain ischemia. The specific neural lineages in the hippocampus were investigated 14 days after ischemia. Some bromodeoxyuridine (BrdU)+ neural progenitor cells in the hippocampus of hypoxic, HI, or sham-operated rats expressed HCNP-pp. Almost half of the BrdU+/HCNP-pp+ cells also expressed the oligodendrocyte lineage marker 2′,3′-cyclic nucleotide 3′-phosphodiesterase, whereas only a few BrdU+/HCNP-pp+ cells in the hippocampus in HI brains expressed the neuronal lineage marker, doublecortin (DCX). Interestingly, no BrdU+/HCNP-pp+ progenitor cells in hypoxic, HI, or sham-operated brains expressed the astrocyte lineage marker, glial fibrillary acidic protein. Together with previous in vitro data, the results of this study suggest that the expression level of HCNP-pp regulates the differentiation of neural progenitor cells into specific neural lineages in the HI hippocampus, indicating that neural stem cell fate can be controlled via the HCNP-pp mediating pathway.