LINK: frontiersin.org/neuroscience/agi … 0015/html/
Some hippocampally-influenced affective and/or cognitive processes decline with aging. The role of androgens in this process is of interest. Testosterone (T) is aromatized to estrogen, and reduced to dihydrotestosterone (DHT), which is converted to 5α-androstane, 3α, 17α-diol (3α-diol). To determine the extent to which some age-related decline in hippocampally-influenced behaviors may be due to androgens, we examined the effects of variation in androgen levels due to age, gonadectomy, and androgen replacement on cognitive (inhibitory avoidance, Morris water maze) and affective (defensive freezing, forced swim) behavior among young (4-months), middle-aged (13-months), and aged (24-months) male rats. Plasma and hippocampal levels of androgens were determined. In experiment 1, comparisons were made between 4-, 13-, and 24-month old rats that were intact or gonadectomized (GDX) and administered a T-filled or empty silastic capsule. There was age-related decline in performance of the inhibitory avoidance, water maze, defensive freezing, and forced swim tasks, and hippocampal 3α-diol levels. Chronic, long-term (1-4 weeks) T-replacement reversed the effects of GDX in 4- and 13-month old, but not 24-month old, rats in the inhibitory avoidance task. Experiments 2 and 3 assessed whether acute subcutaneous T or 3α-diol, respectively, could reverse age-associated decline in performance. 3α-diol, but not T, compared to vehicle, improved performance in the inhibitory avoidance, water maze, forced swim, and defensive freezing tasks, irrespective of age. Thus, age is associated with a decrease in 3α-diol production and 3α-diol administration reinstates cognitive and affective performance of aged male rats.
Does this explain brain fog, apart from the many other side effecs?
T can also be reduced with the 5α-reductase enzyme to dihydrotesterone (DHT), which is subsequently converted by 3α-hydroxy-steroid dehydrogenase (3α−HSD) to the nonaromatizable metabolite, 5α-androstane, 17α-diol (3α-diol). 3α-diol administration, systemically or to the hippocampus of GDX rats, enhances cognitive performance in the inhibitory avoidance, place learning, and object recognition tasks, and decreases anxiety in the elevated plus maze and open field tasks (Frye and Lacey, 2001; Frye et al., 2001; Edinger and Frye, 2004, 2005, 2007; Edinger et al., 2004). Further, blocking T’s metabolism to 3α-diol with indomethacin decreases cognitive performance and increases anxiety behavior of gonadally-intact and/or DHT-replaced rats (Frye and Edinger, 2004; Frye et al., 2004). Together, these findings suggest that T’s beneficial effects on cognitive performance and affective behavior may be due, in part, to its metabolism to 3α-diol in the hippocampus of young rodents.