Hippocampus-specific knockdown of Shati/Nat8l impairs cognitive function and electrophysiological response in mice

Naotaka Izuo; Daiki Ikejima; Kyosuke Uno; Takashi Asano; Shin-Ichi Muramatsu; Atsumi Nitta

doi:10.1016/j.bbrc.2024.150435

Hippocampus-specific knockdown of Shati/Nat8l impairs cognitive function and electrophysiological response in mice

Biochem Biophys Res Commun. 2024 Dec 3:736:150435. doi: 10.1016/j.bbrc.2024.150435. Epub 2024 Jul 22.

Authors

Naotaka Izuo¹, Daiki Ikejima², Kyosuke Uno³, Takashi Asano², Shin-Ichi Muramatsu⁴, Atsumi Nitta⁵

Affiliations

¹ Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan; Laboratory Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904, Japan.
² Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
³ Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan; Laboratory of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, 573-0101, Japan.
⁴ Division of Neurological Gene Therapy, Center for Open Innovation, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan; Center for Gene & Cell Therapy, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo, 108-0071, Japan.
⁵ Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan. Electronic address: nitta@pha.u-toyama.ac.jp.

PMID: 39116682
DOI: 10.1016/j.bbrc.2024.150435

Abstract

Shati/Nat8l was identified as an upregulated molecule in the nucleus accumbens (NAc) of mice following repeated methamphetamine administration. Region-specific roles of this molecule are associated with psychiatric disorders. In the present study, we examined the importance of Shati/Nat8l in the hippocampus because of its high expression in this region. Mice with a hippocampus-specific knockdown of Shati/Nat8l (hippocampal Shati-cKD) were prepared by the microinjection of adeno-associated virus (AAV) vectors carrying Cre into the hippocampus of Shati/Nat8l^flox/flox mice, and their phenotypes were investigated. Drastic reduction in the expression and function of Shati/Nat8l in the hippocampus was observed in Shati-cKD mice. These mice exhibited cognitive dysfunction in behavioral experiments and impaired the electrophysiological response to the stimuli, which elicits long-term potentiation. Shati/Nat8l in the hippocampus is suggested to possibly play an important role in synaptic plasticity to maintain cognitive function. This molecule could be a therapeutic target for hippocampus-related disorders such as dementia.

Keywords: Cognitive function; Hippocampus; N-acetylaspartate; Shati/Nat8l; Synaptic plasticity.

MeSH terms

Acetyltransferases
Animals
Cognition* / physiology
Electrophysiological Phenomena
Gene Knockdown Techniques*
Hippocampus* / metabolism
Hippocampus* / physiology
Long-Term Potentiation
Male
Mice
Mice, Inbred C57BL
Neuronal Plasticity / genetics

Substances

Shati protein, mouse
Acetyltransferases