Neuroscience
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Losses of working and long-term memory are hallmarks of human aging and may signal impending neurodegenerative disease. The maintenance of neural elements in brain systems that support memory, such as synapse formation in prefrontal cortex and hippocampus, are critical for cognitive health in aging. This paper reviews the biological basis for androgens as neuroprotectants or neuromodulators in aging and the importance of androgens on the brain systems important for memory. ⋯ In addition, the conversion of testosterone to its androgen metabolites or to estradiol may play a special role in the preservation of memory in aging. This paper reviews discrepancies between studies using animal models and studies of human cognition, and suggests new directions that are likely to be fruitful in the future for understanding the role of androgens in brain aging. This review suggests that studies of low androgen levels in older men may not index the same biological mechanisms and behavioral effects as the studies of gonadectomy in animal models.
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Progestins mediate the onset and duration of lordosis, the mating posture of female rodents, through actions in the hypothalamus and ventral tegmental area. In the hypothalamus, progesterone has traditional, "genomic" actions via intracellular progestin receptors. ⋯ Data are reviewed that support the notion that: 1) effects of 3alpha-hydroxy-5alpha-pregnan-20-one in the midbrain ventral tegmental area facilitate lordosis and other reproductively-relevant behaviors. 2) 3alpha-Hydroxy-5alpha-pregnan-20-one, formed in the ventral tegmental area from metabolism of progestins, produced peripherally by endocrine glands, or centrally from biosynthesis in glial cells mediates socio-sexual behaviors. 3) 3alpha-Hydroxy-5alpha-pregnan-20-one's actions at GABA(A)/benzodiazepine receptors, NMDA type glutamate receptors, and dopamine receptors in the ventral tegmental area are important for lordosis; however, effects at these substrates on socio-sexual behaviors have not been elucidated. Given 3alpha-hydroxy-5alpha-pregnan-20-one's involvement in stress responses, its putative role as a homeostatic regulator and in the pathophysiology and treatment of neuropsychiatric disorders is discussed.