Possible correlated variation of GABAA receptor α3 expression with hippocampal cholinergic neurostimulating peptide precursor protein in the hippocampus

Kenichi Adachi; Daisuke Kato; Tomoaki Kahyo; Tomokazu Konishi; Toyohiro Sato; Yuta Madokoro; Masayuki Mizuno; Hiroyasu Akatsu; Mitsutoshi Setou; Noriyuki Matsukawa

doi:10.1016/j.bbrc.2021.01.010

Possible correlated variation of GABA_A receptor α3 expression with hippocampal cholinergic neurostimulating peptide precursor protein in the hippocampus

Biochem Biophys Res Commun. 2021 Jan 24:542:80-86. doi: 10.1016/j.bbrc.2021.01.010. Online ahead of print.

Authors

Affiliations

¹ Department of Neurology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan.
² Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan. Electronic address: daikato@med.nagoya-u.ac.jp.
³ Department of Cellular and Molecular Anatomy and International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan.
⁴ Faculty of Bioresource Sciences, Akita Prefectural University, Akita, 010-0195, Japan.
⁵ Department of Community-based Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan.
⁶ Department of Neurology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan. Electronic address: norim@med.nagoya-cu.ac.jp.

PMID: 33503541
DOI: 10.1016/j.bbrc.2021.01.010

Abstract

Cholinergic neural activation from the medial septal nucleus to hippocampus plays a crucial role in episodic memory as a regulating system for glutamatergic neural activation in the hippocampus. As a candidate regulating factor for acetylcholine synthesis in the medial septal nucleus, hippocampal cholinergic neurostimulating peptide (HCNP) was purified from the soluble fraction of young adult rat hippocampus. HCNP is released from its precursor protein (HCNP-pp), also referred to as phosphatidylethanolamine-binding protein 1. We recently reported that HCNP-pp conditional knockout (KO) mice, in which the HCNP-pp gene was knocked out at 3 months of age by tamoxifen injection, display no significant behavioral abnormalities, whereas HCNP-pp KO mice have a diminished cholinergic projection to CA1 and a decreased of theta activity in CA1. In this study, to address whether HCNP-pp reduction in early life is associated with behavioral changes, we evaluated the behavior of HCNP-pp KO mice in which HCNP-pp was downregulated from an early phase (postnatal days 14-28). As unexpected, HCNP-pp KO mice had no behavioral deficits. However, a significant positive correlation between HCNP-pp and gamma-aminobutyric acid A (GABA_A) receptor α3 subunit mRNA expression was found in individuals. This finding suggests involvement of HCNP-pp in regulating GABA_A receptor α3 gene expression.

Keywords: Cholinergic neuron; GABA(A) receptor α3; Hippocampal cholinergic neurostimulating peptide (HCNP); Hippocampal cholinergic neurostimulating peptide precursor protein (HCNP-pp); Phosphatidylethanolamine-binding protein 1.