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

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: 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 version of the paper has not been formally peer reviewed.