摘要：SummaryNeuroactive 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 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 the occurrence of these neurosteroids in the mouse hippocampus after spatial-learning tasks.Cyp7b1deficiency impaired remote spatial memory with recent memory mostly unaffected. The hippocampal dendritic spine densities were reduced inCyp7b1-deficient mice, and they were no more increased by the training. Furthermore, chronic intracerebroventricular administration of a mixture of 7α-OH-Preg and 7α-OH-DHEA rescued the deteriorated remote memory performance inCyp7b1-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.Graphical AbstractDisplay OmittedHighlights•LC-MS/MS analysis identified 7α-hydroxylated neurosteroids in the mouse hippocampus•The hippocampal neurosteroids were induced by spatial water maze training•KO of 7α-hydroxylating enzyme impaired remote memory and hippocampal spine density•Infusion of the 7α-hydroxylated steroids to the KO rescued impaired remote memoryBiological Sciences; Neuroscience; Cellular Neuroscience
