Rapid nongenomic modulation by neurosteroids of dendritic spines in the hippocampus: Androgen, oestrogen and corticosteroid

Abstract

Memories are stored in synapses that consist of axon terminals and dendritic spines.Dendritic spines are postsynaptic structures of synapses and are essential for synaptic plasticity and cognition. Therefore, extensive investigations concerning the functions and structures of spines have been performed. Sex steroids and stress steroids have been shown to modulate hippocampal synapses. Although the rapid modulatory action of sex steroids on synapses has been studied in hippocampal neurones over several decades, the essential molecular mechanisms have not been fully understood.Here, a description of kinase-dependent signalling mechanisms is provided that can explain the rapid nongenomic modulation of dendritic spinogenesis in rat and mouse hippocampal slices by the application of sex steroids, including dihydrotestosterone, testosterone, oestradiol and progesterone. We also indicate the role of synaptic (classic) sex steroid receptors that trigger these rapid synaptic modulations. Moreover, we describe rapid nongenomic spine modulation by applying corticosterone, which is an acute stress model of the hippocampus. The explanations for the results obtained are mainly based on the optical imaging of dendritic spines. 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 recognise that most of rapid effects of exogenously applied oestrogen and androgen were observed in steroid-depleted conditions, including acute slices of the hippocampus, castrated male animals and ovariectomised female animals. Therefore, the previously observed effects can be considered as a type of recovery event, which may be essentially similar to hormone replacement therapy under hormone-decreased conditions. On the other hand, in gonadally intact young animals with high levels of endogenous sex hormones, further supplementation of sex hormones might not be effective, whereas the infusion of blockers for steroid receptors or kinases may be effective, with respect to suppressing sex hormone functions, thus providing useful information regarding molecular mechanisms. K E Y W O R D Sandrogens, cortisol/corticosterone, glucocorticoids, membrane/nuclear receptors, neuroactive steroids, oestrogens, steroids

The challenge hypothesis revisited: Focus on reproductive experience and neural mechanisms

“…Several studies indicate that androgens can promote spatial memory formation (Benice and Raber, 2009;McConnell et al, 2012;Wagner et al, 2018), but most have applied long-term manipulations through gonadectomy or implants. However, T can act rapidly to increase spine density in hippocampal CA1 neurons (Hatanaka et al, 2015;Murakami et al, 2018), which are important for the formation and retrieval of spatial memories. This suggests the possibility that T pulses could modulate spatial memory formation.…”

Anabolic-androgenic steroids cycle administration decreases anxious-like behavior but does not affect long-term memory acquisition in rats

“…The influence of testosterone on learning processes and the acquisition of various types of memory, in different experimental models, have been reported throughout the years. It is well known that testosterone and its metabolites, dihydrotestosterones, are able to modulate the behavioral biochemical metabolism, which reflects, among other effects, on the maintenance of the net hippocampal synaptic density, considered an important factor to allow the memory acquisition and learning (Murakami et al, 2018).…”

New perspectives for the action of steroids in the brain

“…These rapid synaptic modulations are mediated by sex steroid receptors, including rapid nongenomic effects. In the review by Murakami et al, the results from the optical imaging of dendritic spines are discussed, together with results obtained from other types of imaging techniques, including electron microscopic imaging.…”

“…The review by Sheppard et al19 examines recent developments in the study of the rapid effects of 17β-oestradiol and ER agonists on learning and memory tasks in female rodents, including the activation of intracellular signalling cascades and epigenetic processes.The rapid nongenomic modulation of dendritic spinogenesis in rat and mouse hippocampal slices is mediated by sex steroids, including dihydrotestosterone, testosterone, oestradiol and progesterone.These rapid synaptic modulations are mediated by sex steroid receptors, including rapid nongenomic effects. In the review by Murakami et al,20 the results from the optical imaging of dendritic spines are discussed, together with results obtained from other types of imaging techniques, including electron microscopic imaging.Relationships between spine modulation and the modulation of cognition are also discussed. The anti-inflammatory action of neuroactive steroids is discussed in the next 2 reviews.…”