Training-Induced 7α-Hydroxylated Neurosteroids in Mouse Hippocampus Bolster Remote Spatial Memory
28 Pages Posted: 12 May 2020 Sneak Peek Status: Review CompleteMore...
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
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