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Review
, 34 Suppl 1 (Suppl 1), S143-61

Neurosteroids' Effects and Mechanisms for Social, Cognitive, Emotional, and Physical Functions

Affiliations
Review

Neurosteroids' Effects and Mechanisms for Social, Cognitive, Emotional, and Physical Functions

Cheryl A Frye. Psychoneuroendocrinology.

Abstract

Hormones are trophic factors that integrate central and peripheral nervous system functions, and can influence social, cognitive, emotional and physical (SCEP) processes. Greater understanding of behavioral and neurobiological underpinnings of mental, cognitive, and/or physical changes with maturation is becoming increasingly important as the world's population ages. There are individual differences in how people age, but the factors that influence these differences are not well understood. Social supports are one factor that may influence the trajectory of age-related processes. The loss of close relationships, especially among older persons, is one of the greatest risk factors for mental and physical decline. Progesterone, secreted by the ovaries, or produced de novo in the brain, is readily converted centrally to 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), and can influence SCEP, through rapid, non-classical steroid-mediated actions. Our hypothesis is that 3alpha,5alpha-THP is a key trophic factor in SCEP and development. Our research has demonstrated that 3alpha,5alpha-THP facilitates social and sexual behavior of rodents, which evokes further increases in 3alpha,5alpha-THP in midbrain and hippocampus, brain areas involved in SCEP. The role of 3alpha,5alpha-THP to influence social and/or sexual experience, and thereby SCEP, is discussed in this review. Further understanding of these neurobiological and/or behavioral factors may lead to findings that ultimately can promote health and prevent disease.

Figures

Figure 1
Figure 1
Sexual behavior correlates with 3α,5α-THP levels in the midbrain of young (diestrous or proestrous) or ovx (estradiol (E) and progesterone (P) with or without inhibition of 3α,5α-THP formation, or 3α,5α-THP) rats. Bars represent lordosis quotients (mean±SEM) and dots represent 3α,5α-THP levels (ng/g±SEM) in midbrain.
Figure 2
Figure 2
Anti-depression behavior in the Porsolt forced swim task is greater among intact male and female adult rats compared to juvenile male and females rats. It is greater among proestrous or pregnant rats, compared to diestrous or post-partum rats. As well, it is greater among middle-aged reproductively competent rats compared to middle-aged rats that are reproductively senescent or transition to senescence. * indicates different from respective juvenile, diestrous, post-partum, or reproductively-senescent control, p < 0.05.
Figure 3
Figure 3
Anti-anxiety behavior on the elevated plus maze correlates with 3α,5α-THP in hippocampus of young (diestrous or proestrous), mid-aged (reproductively-competent or reproductively-senescent), or OVX (progesterone (P) with/without 3α,5α-THP inhibition, or 3α,5α-THP administration) rats. Bars represent open arm time (seconds±SEM) and dots represent 3α,5α-THP levels (ng/g±SEM) in hippocampus.
Figure 4
Figure 4
Cognitive performance on the object recognition task correlates with 3α,5α-THP levels in the cortex of young (diestrous or proestrous), mid-aged (reproductively-competent or reproductively-senescent), or OVX (progesterone (P) with/without 3α,5α-THP inhibition, or 3α,5α-THP administration) rats. Bars represent time with the novel object (seconds±SEM) and dots represent 3α,5α-THP levels (ng/g±SEM) in cortex.
Figure 5
Figure 5
Depicts 3α,5α-THP levels in serum, midbrain, hippocampus, diencephalon, and cortex of proestrous or diestrous rats that engaged in paced mating or not (top), proestrous rats that engaged in exploratory (open field and elevated plus maze) or social (partner preference and social interaction) or no tasks with paced mating (middle), and proestrous rats that engage in only one task from above (open field, elevated plus maze, partner preference, social interaction, or no task) with paced mating (bottom). Line indicates performance of non-mated diestrous (top) or proestrous (middle, bottom) control. * indicates different from control, p < 0.05.
Figure 6
Figure 6
Ovariectomized, vehicle or estradiol (E)-primed multiparous rats have greater anti-anxiety behavior in the elevated plus maze than do nulliparous rats. Line indicates performance of nulliparous, vehicle-administered control. * indicates different from control, p < 0.05.
Figure 7
Figure 7
Naturally-cycling, proestrous or multiparous rats outperform diestrous nulliparous rats in the object recognition task. Line indicates performance of diestrous, nulliparous control. * indicates different from control, p < 0.05.
Figure 8
Figure 8
Among middle-aged rats, reproductively-competent rats had greater lordosis and proceptivity in a paced-mating task than did rats that were reproductively-senescent or transitioning to reproductive-senescence. Line indicates performance of reproductively-competent rats.
Figure 9
Figure 9
Among middle-aged rats, reproductively-competent rats had greater cognitive performance in the object recognition task (left) and were faster to locate a hidden platform in the Morris water maze (right) compared to rats that were reproductively-senescent or transitioning to reproductive-senescence. Line indicates performance of reproductively-competent rats.* indicates different from control (p < 0.05). # indicates tendency to be different from control (p < 0.10).
Figure 10
Figure 10
Among middle-aged rats, reproductively-competent rats had greater anti-anxiety behavior in an elevated plus maze than did rats that were reproductively-senescent or transitioning to reproductive-senescence. Line indicates performance of reproductively-competent rats. * indicates different from control, p < 0.05.
Diagram 1
Diagram 1
Sources of 3α,5α-THP in the CNS include de novo biosynthesis in glial cells and metabolism of peripheral or central P.
Diagram 2
Diagram 2
Depicts cholesterol transport into mitochondrion via PBR and enzymatic processes involved in neurosteroidogenesis.

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