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Training-Induced 7α-Hydroxylated Neurosteroids in Mouse Hippocampus Bolster Remote Spatial Memory

28 Pages Posted: 12 May 2020 Sneak Peek Status: Review Complete

See all articles by Kanako Maehata

Kanako Maehata

University of Tokyo - Department of Biological Sciences

Kimiko Shimizu

University of Tokyo - Department of Biological Sciences

Tomoko Ikeno

University of Tokyo - Department of Biological Sciences

Ayaka Sakurai

University of Tokyo - Department of Biological Sciences

Qiuyi Wang

Osaka University

Toshifumi Takao

Osaka University

Yoshitaka Fukada

University of Tokyo - Department of Biological Sciences

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Abstract

Neuroactive steroids, termed neurosteroids, are synthesized locally in the brain and influence   biological functions, including cognition and behavior. These neurosteroids are synthesized from cholesterol by a series of cytochrome P450 enzymes, among which a new member of P450 hydroxylase, cytochrome P450-7b1 (CYP7B1), catalyzes the formation of 7α-hydroxylated neurosteroids, 7α-hydroxypregnenolone (7α-OH-Preg) and 7α-hydroxydehydroepiandrosterone (7α-OH-DHEA). Here we demonstrated for the first time the occurrence of these two neurosteroids in the mouse hippocampus only after spatial-learning tasks. Cyp7b1-deficiency in mice impaired remote spatial memory without affecting recent memory and prevented training induced increase of dendritic spine density in the hippocampus. Furthermore, chronic intracerebroventricular administration of a mixture of 7α-OH-Preg and 7α-OH-DHEA rescued the deteriorated remote memory performance in Cyp7b1-deficient mice. It is concluded that the 7α-hydroxylated neurosteroids are required for long-term maintenance of spatial memory, and we suggest that these neurosteroids may induce synaptic remodeling to maintain the hippocampal function.

Keywords: Neurosteroid, 7α-hydroxypregnenolone, 7α-hydroxydehydroepiandrosterone, CYP7B1, remote memory, spatial memory, spine density

Suggested Citation

Maehata, Kanako and Shimizu, Kimiko and Ikeno, Tomoko and Sakurai, Ayaka and Wang, Qiuyi and Takao, Toshifumi and Fukada, Yoshitaka, Training-Induced 7α-Hydroxylated Neurosteroids in Mouse Hippocampus Bolster Remote Spatial Memory. Available at SSRN: https://ssrn.com/abstract=3583660 or http://dx.doi.org/10.2139/ssrn.3583660
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Kanako Maehata

University of Tokyo - Department of Biological Sciences ( email )

Tokyo
Japan

Kimiko Shimizu (Contact Author)

University of Tokyo - Department of Biological Sciences ( email )

Tokyo
Japan

Tomoko Ikeno

University of Tokyo - Department of Biological Sciences ( email )

Tokyo
Japan

Ayaka Sakurai

University of Tokyo - Department of Biological Sciences ( email )

Tokyo
Japan

Qiuyi Wang

Osaka University

1-1 Yamadaoka
Suita
Osaka, 565-0871
Japan

Toshifumi Takao

Osaka University

1-1 Yamadaoka
Suita
Osaka, 565-0871
Japan

Yoshitaka Fukada

University of Tokyo - Department of Biological Sciences ( email )

Tokyo
Japan

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