Oestrogens and the structural and functional plasticity of neurons: implications for memory, ageing and neurodegenerative processes.

Oestrogens have numerous effects on the brain, beginning during gestation and continuing on into adulthood. Many of these actions involve areas of the brain that are not primarily involved in reproduction, such as the basal forebrain, hippocampus, caudate putamen, midbrain raphe and brainstem locus coeruleus. This paper describes three actions of oestrogens that are especially relevant to brain mechanisms involved in memory processes and their alterations during ageing and neurodegenerative diseases: (1) the regulation of cholinergic neurons by oestradiol in the rat basal forebrain, involving induction of choline acetyltransferase and acetylcholinesterase according to a sexually dimorphic pattern; (2) the regulation of synaptogenesis in the CA1 region of the hippocampus by oestrogens and progestins during the four- to five-day oestrus cycle of the female rat. Formation of new excitatory synapses is induced by oestradiol and involves N-methyl-D-aspartate receptors; removal of these synapses involves intracellular progestin receptors; (3) sex differences in hippocampal structure, which may help to explain differences in the strategies that male and female rats use to solve spatial navigation problems. During the period of development when testosterone is elevated in the male, aromatase and oestrogen receptors are also elevated, making it likely that this pathway is involved in the masculinization of hippocampal structure.