Rapid non-genomic modulation by neurosteroids of dendritic spines in the hippocampus: androgen, estrogen and corticosteroid

Abstract

Memories are stored in synapses which consist of axon terminals and dendritic spines. Dendritic spines are postsynaptic structures of synapses and essential for synaptic plasticity and cognition. Therefore, extensive investigations about functions and structures of spines have been performed. Sex steroids and stress steroids have been shown to modulate hippocampal synapses.

Although rapid modulatory action of sex steroids on synapses has been studied in hippocampal neurons over several decades, its essential molecular mechanisms have not been fully understood. We here describe kinase-dependent signaling mechanisms which can well explain the rapid non-genomic modulation of dendritic spinogenesis in rat and mouse hippocampal slices by application of sex steroids, including dihydrotestosterone (DHT), testosterone (T), estradiol (E2) and progesterone (PROG). We also indicate the role of synaptic (classic) sex steroid receptors which trigger these rapid synaptic modulations. Moreover, we describe rapid non-genomic spine modulation by applying corticosterone (CORT), which is an acute stress model of the hippocampus.

The explanations of results are mainly based on the results from optical imaging of dendritic spines, and comparisons are also performed with results obtained from other types of imaging, including electron microscopic imaging. Relationships between spine modulation and modulation of cognition are discussed.

We can realize that most of rapid effects of exogenously applied estrogen and androgen were observed in steroid-depleted conditions, including acute slices of the hippocampus, castrated male animals and ovariectomized female animals. Therefore, the previously observed effects can be recognized as a kind of recovery events which may be essentially similar to hormone replacement therapy in hormone-declined condition. On the other hand in gonadally intact young animals with high level of endogenous sex hormones, further supplementation of sex hormones might not be effective, but rather infusion of blockers for steroid receptors or kinases may be effective to suppress sex hormone functions, leading to find useful information regarding molecular mechanisms.

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