Impairment of cognitive function induced by Shati/Nat8l overexpression in the prefrontal cortex of mice

Meriem Haddar; Katsunori Azuma; Naotaka Izuo; Uno Kyosuke; Takashi Asano; Shin-Ichi Muramatsu; Atsumi Nitta

doi:10.1016/j.bbr.2020.112938

Impairment of cognitive function induced by Shati/Nat8l overexpression in the prefrontal cortex of mice

Behav Brain Res. 2021 Jan 15:397:112938. doi: 10.1016/j.bbr.2020.112938. Epub 2020 Sep 28.

Authors

Meriem Haddar¹, Katsunori Azuma¹, Naotaka Izuo¹, Uno Kyosuke², Takashi Asano¹, Shin-Ichi Muramatsu³, Atsumi Nitta⁴

Affiliations

¹ Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
² Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama, Japan; Laboratory of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata-shi, Osaka, Japan.
³ Division of Neurological Gene Therapy, Open Innovation Center, Jichi Medical University, Shimotsuke, Japan; Center for Gene & Cell Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁴ Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama, Japan. Electronic address: nitta@pha.u-toyama.ac.jp.

PMID: 32998043
DOI: 10.1016/j.bbr.2020.112938

Abstract

A novel N-acetyltransferase, Shati/Nat8l, was identified in the brains of mice exposed to methamphetamine. Shati/Nat8l overexpression in the medial prefrontal cortex (mPFC) was found to attenuate methamphetamine-induced dependence. The mPFC is a brain region that plays an important role in cognitive function. However, the effect of Shati/Nat8l on cognition and memory has not yet been clarified. To understand the role of Shati/Nat8l in memory, we generated C57BL/6J mice with overexpressed Shati/Nat8l in the mPFC and performed memory-related experiments, including novel object-location and object-in-context tests. Furthermore, we used quantitative immunohistochemistry to assess the presynaptic and postsynaptic proteins, synaptophysin and postsynaptic density protein (PSD)-95, respectively. Shati/Nat8l overexpression in the mPFC impaired both novel object-location and object-in-context memory. Moreover, Shati/Nat8l overexpression in the mPFC reduced PSD-95 levels, but not synaptophysin levels in the mPFC. These results demonstrated that Shati/Nat8l overexpression in the mPFC is involved in location and contextual memory, and can affect the excitatory postsynaptic protein, PSD-95.

Keywords: Memory; PSD-95; Shati/Nat8l; Synaptophysin; mPFC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetyltransferases / metabolism*
Animals
Cognitive Dysfunction / metabolism*
Cognitive Dysfunction / physiopathology*
Disks Large Homolog 4 Protein / metabolism*
Male
Memory / physiology*
Mice
Mice, Inbred C57BL
Prefrontal Cortex / metabolism*
Spatial Memory / physiology
Synaptophysin / metabolism*

Substances

Disks Large Homolog 4 Protein
Dlg4 protein, mouse
Synaptophysin
Syp protein, mouse
Acetyltransferases
Shati protein, mouse