Abstract
Modulation of synapses under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. We tried to test whether rapid CORT effects involve activation of essential kinases as non-genomic processes. We demonstrated rapid effects (~1 h) of CORT on the density of thorns, by imaging Lucifer Yellow-injected neurons in adult male rat hippocampal slices. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. The application of CORT at 100, 500, and 1000 nM induced a rapid increase in the density of thorns in the stratum lucidum of CA3 pyramidal neurons. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, including MAPK, PKA, or PKC, suppressed CORT-induced enhancement of thorn-genesis. On the other hand, GSK-3β was not involved in the signaling of thorn-genesis. Blocking AMPA receptors suppressed the CORT effect. Expression of CA3 synaptic/extranuclear GR was demonstrated by immunogold electron microscopic analysis. From these results, stress levels of CORT (100–1000 nM) might drive the rapid thorn-genesis via synaptic/extranuclear GR and multiple kinase pathways, although a role of nuclear GRs cannot be completely excluded.
Highlights
Functions and architectures of mammalian hippocampus are altered or modulated under the stressful conditions
We investigated the effect of CORT on the modulation of the thorn density in the hippocampus CA3 stratum lucidum
In CORT-treatment group, the enhancing effect was significant at 1 μM CORT (3.2 thorns/μm) compared with 10 nM (2.4 thorns/μm), 30 nM CORT (30 nM) (2.9 thorns/μm), 100 nM CORT (100 nM) (3.0 thorns/μm), and 500 nM CORT (500 nM) (3.3 thorns/μm) CORT
Summary
Functions and architectures of mammalian hippocampus are altered or modulated under the stressful conditions. The chronic stress-induced increase in CORT slowly produces neuronal cell damage in the hippocampus. Chronic restraint stress has induced retraction of thorny excrescences, which has subsequently been reversed after water maze training. Water maze training alone has increased the volume of thorny excrescence as well as the number of thorns per thorny excrescence (Stewart et al, 2005). These slow steroid effects may be mediated by nuclear receptors. Upon binding of steroids to nuclear GR, GR forms dimer and bind to the glucocorticoid response element of genes, resulting in modulation of protein synthesis
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