Moderate Hypogonadism Enhances Hippocampal Neurotransmission, Augments Memory and Learning and Modulates Neurogenesis in Adult Male Rats.

The study aimed to test whether the decrease in testosterone level during aging is the
underlying mechanism for the deterioration in memory and cognitive functions. This
was achieved through determination of hippocampal neurotransmission by in vivo
determination of extracellular dopamine and serotonin in CA1 hippocampal region
and brain derived neurotorphic factor (BDNF) synthesis in both normal and
unilateral castrated rats (an experimental model for hypogonadism) and 2 and 4 days
after single dose of exemestane (5mg/kg, p.o.). In addition, learning and memory
processes were determined using Morris water maze. Results showed that unilateral
castration resulted in significant decrease in testosterone level, disturbing the
testosterone/estradiol ratio and enhanced hippocampal neurotransmission. Besides,
these effects were accompanied with an enhanced learning and memory and
significant decrease in the level of BDNF expression. Whereas, exemestane treatment
increased testosterone level and inhibited DA and 5-HT release, significantly
increased BDNF expression and inhibited learning and memory processes in both
normal and unilateral castrated groups. The study indicated that moderate
hypogonadism has a positive effect on hippocampal neurotransmission, learning and
memory due to the imbalance of testosterone/estradiol in favor of estradiol. On the
other hand, exemestane effects might be due to imbalance of testosterone/estradiol
ratio in favor of testosterone. In addition, it seems that the beneficial effects of
physiological levels of testosterone are indirectly due its conversion to estradiol.
Moreover, the study indicated that moderate decline in endogenous testosterone in
healthy aged individuals is not the underlying mechanism of the age-related
deterioration in the cognitive function.