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 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. Cyp7b1 deficiency impaired remote spatial memory with recent memory mostly unaffected. The hippocampal dendritic spine densities were reduced in Cyp7b1-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 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.

神经活性类固醇，称为神经类固醇，是在大脑中局部合成的，会影响生物学功能，包括认知和行为。这些神经固醇是由胆固醇通过一系列细胞色素P450酶合成的，其中P450羟化酶的一个成员细胞色素P450-7b1（CYP7B1）催化7α-羟基化神经固醇，7α-羟基孕烯醇酮（7α-OH-Preg）和7α-羟基脱氢表雄酮（7α-OH-DHEA）。在这里，我们证明了在进行空间学习任务后，这些神经甾体在小鼠海马中的发生。Cyp7b1缺陷会损害远程空间记忆，而近期记忆几乎不会受到影响。Cyp7b1降低了海马树突棘密度缺陷的小鼠，并且训练后它们不再增加。此外，长期脑室内给予7α-OH-Preg和7α-OH-DHEA的混合物可挽救Cyp7b1缺陷小鼠的远程记忆功能。结论是长期维持空间记忆需要7α-羟基化神经甾体，我们建议这些神经甾体可能诱导突触重塑以维持海马功能。