Testosterone and Adult Neurogenesis

Abstract

It is now well established that neurogenesis occurs throughout adulthood in select brain regions, but the functional significance of adult neurogenesis remains unclear. There is considerable evidence that steroid hormones modulate various stages of adult neurogenesis, and this review provides a focused summary of the effects of testosterone on adult neurogenesis. Initial evidence came from field studies with birds and wild rodent populations. Subsequent experiments with laboratory rodents have tested the effects of testosterone and its steroid metabolites upon adult neurogenesis, as well as the functional consequences of induced changes in neurogenesis. These experiments have provided clear evidence that testosterone increases adult neurogenesis within the dentate gyrus region of the hippocampus through an androgen-dependent pathway. Most evidence indicates that androgens selectively enhance the survival of newly generated neurons, while having little effect on cell proliferation. Whether this is a result of androgens acting directly on receptors of new neurons remains unclear, and indirect routes involving brain-derived neurotrophic factor (BDNF) and glucocorticoids may be involved. In vitro experiments suggest that testosterone has broad-ranging neuroprotective effects, which will be briefly reviewed. A better understanding of the effects of testosterone upon adult neurogenesis could shed light on neurological diseases that show sex differences.

Keywords: BDNF; adult neurogenesis; androgen; dentate gyrus; hippocampus; neuroprotection; spatial memory; sub-ventricular zone; testosterone.

Figure 1

Key sex steroid synthesis pathways found in the gonads and the brain. Enzyme name abbreviations are as follows: P450 side-chain cleavage enzyme (P455scc), 17α-hydroxylase [P450(17α)], 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), 3α-hydroxysteroid dehydrogenase (3α-HSD), and P450 aromatase (P450arom) [48,52,54].