Fig. 3

Suggested non-genomic, intracellular mechanisms driving dendritic spine changes and neurogenesis by estrogens. We hypothesize that estrogens bind to estrogen receptors (membrane bound or intracellular) which go on to activate cell signalling pathways, including, but not limited to the ERK, PI3K, JNK, and/or mTOR pathways. Cross-talk between these pathways is common. These have downstream effects on a number of intracellular mechanisms, including protein synthesis and actin polymerization. Through actin polymerization and protein synthesis, novel spines or “silent” synapses are created, which can become mature synapses following neuronal activity. If unused, the novel spines do not mature and are instead re-internalized. Other intracellular mechanisms, such as epigenetic or post-translational protein modifications and mediation of neurotransmitters and/or receptors, are likely also involved. The contributions of cell signalling pathways and other intracellular mechanisms in the effects of estrogens on neurogenesis remain to be explored