Scientists from Middlebury College (USA) studied how testosterone affects the survival of new nerve cells in the brains of adult male rats. The work was published in the journal Neuroscience. This is a preclinical animal study, so the findings cannot be directly transferred to humans.
The adult brain produces new neurons from stem cells - a process called neurogenesis. It occurs mainly in the hippocampus, the region responsible for learning, memory and stress regulation. About half of newborn cells die in the first month before they can integrate into the brain's network.
Testosterone, the main male sex hormone, declines with age. Low levels are linked to an increased risk of memory decline and dementia, although clinical trials of testosterone therapy in older men have produced conflicting results.
In earlier experiments, removal of the testes in rats did not change the number of new cells but sharply reduced their survival. Daily testosterone injections for 30 days restored the measure. Shorter courses had no effect, while a brief surge of the hormone at an early stage of cell development, on the contrary, improved survival. The authors set out to determine whether the duration of exposure or the sensitivity of cells at certain periods matters.
The new experiment involved adult male Sprague-Dawley rats. All animals were castrated to control hormone levels and housed individually. Each received a synthetic substance, BrdU, which incorporates into the DNA of dividing cells and makes it possible to track specifically the generation of cells born at the time of injection.
The rats were then divided into groups: some received testosterone at a high physiological dose, others received neutral oil. Injections were given at different times: during the first half of the cell maturation period, during the second half, or for all 30 days. Later, blood was taken from the animals and the brain was examined under a microscope, counting surviving labeled cells.
It turned out that across the dentate gyrus of the hippocampus (the area where new neurons are born), only the full 30-day course of testosterone produced a significant increase in surviving cells. Later administration showed a trend toward an increase that did not reach statistical significance, while early administration had no effect.
Separate analysis of the dorsal (upper/anterior) and ventral (lower/posterior) parts showed that in the dorsal zone, responsible for spatial memory, testosterone increased survival both with the full course and with late administration. In the ventral zone, associated with stress, there was no effect in any regimen.
Most surviving labeled cells in all groups matured into neurons. This means the hormone did not change the proportion of cells becoming neurons but increased their total number.
The authors are cautious in their conclusions: the work was conducted on castrated rats in isolation, which does not replicate the gradual age-related decline in the hormone in men. The statistics on timing rely on small groups, and molecular mechanisms were not studied. Nevertheless, the researchers suggest that testosterone may help preserve new neurons at later stages of their development, and this should be taken into account in future clinical work.