Hippocampal 7α-Hydroxylated Neurosteroids Are Raised by Training and Bolster Remote Spatial Memory with Increase of the Spine Densities

Abstract

Summary 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.

Are there sex differences in spatial reference memory in the Morris water maze? A large-sample experimental study

“…Here, we have found sex differences in habituation, revealing that female rats reached the platform faster than males. These results reflect the need to include habituation in spatial memory tasks, which is commonly performed in a similar way to this study (Anderson et al, 2013 ; Arias et al, 2012 ; Conejo et al, 2010 ), only to swimming activity (Bert et al, 2002 ; Nategh et al, 2015 ) or to platform exploration (Maehata et al, 2020 ). Regarding habituation analysis, we can hypothesize that the swimming speed was higher in females not only during the acquisition trials, but also during the habituation.…”

Artemisia argyi exhibits anti-aging effects through decreasing the senescence in aging stem cells

“…The spatial recognition ability and memory of the animal was assessed using Morris water maze test [ 45 ]. The setup consists of a large circular pool (diameter 160cm; height 30cm) and filled with water (25° C) in which an escape platform (12 cm in width) was hidden 0.5 cm below the water surface and visibility was reduced by adding milk to water.…”

“…The spatial recognition ability and memory of the animal was assessed using Morris water maze test [45].…”

25-Hydroxycholesterol in health and diseases

“…At the direct neuronal level, recent studies have investigated the effects of Cyp7b1 deletion in mice and reported few or no impact on cognitive functions and neuronal morphology despite the high level of 25-HC in plasma ( 147 , 148 ). However, direct treatment of neurons with 25-HC decreases neurites, neurons viability, metabolism, and disrupts hippocampal synaptic transmission via N-methyl-D-aspartate receptor -mediated metaplasticity ( 149 , 150 ).…”