Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuropeptide corticotropin-releasing factor (CRF) coordinates the endocrine responses to stress as a major physiological regulator of the hypothalamic-pituitary-adrenal axis. We assessed the effect of the non-peptidergic CRF receptor 1 antagonist CP-154,526 on stress-induced changes in context-dependent fear conditioning and hippocampal synaptic plasticity. The learning impairment of mice trained immediately after 1 h immobilization could be overcome by preinjection of CP-154,526 before exposure to immobilization. Exposure to acute stress reduced the amount of autophosphorylated Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in the hippocampal CA1 area. When animals were pretreated with CP-154,526 before immobilization, the amount of hippocampal autophosphorylated CaMKII was elevated. Electrophysiological studies in the hippocampal CA1 region of stressed animals revealed no significant effects of the CP-154,526 pretreatment on long-term potentiation but a significant elevation of paired-pulse facilitation (PPF) was observed. The CP-154,526-induced enhancements in fear conditioning and PPF could be prevented by the selective CaMKII inhibitor KN-62. Our results demonstrated that learning impairment after acute stress was antagonized by CP-154,526 pretreatment.
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PMID:The corticotropin-releasing factor receptor 1 antagonist CP-154,526 reverses stress-induced learning deficits in mice. 1252 51

The phosphorylation of calcium/calmodulin-dependent protein kinase (CaMK) II, induced by an increase in the intracellular Ca2+ concentration, is involved in the alteration of brain functions such as memory formation. In the present study, we examined the influence of various immobilization stress paradigms on the phosphorylation of CaMKII (phospho-CaMKII) and CaMKII levels in the rat hippocampus. Immunoblot and immunohistochemical analyses were performed to examine the levels of CaMKII and phospho-CaMKII. Real-time quantitative polymerase chain reaction (PCR) was performed to analyse the mRNA levels of N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subtypes. Acute (single) and repeated (4 d), but not chronic (14 d), stress exposure of 45 min or longer duration significantly increased phospho-CaMKII levels without affecting the levels of CaMKII. Pre-treatment with NBQX, a selective AMPA receptor antagonist, significantly prevented this stress-induced increase. In contrast, two NMDA receptor antagonists, LY235959 and MK-801, showed no inhibitory effect on phospho-CaMKII levels during acute stress. Neither acute nor chronic stress changed mRNA levels of NMDA and AMPA receptors. These results demonstrate that immobilization stress promotes the phosphorylation of CaMKII. The increase in the intracellular Ca2+ concentration by the activation of AMPA receptors may play a role in the stress-induced phospho-CaMKII in the rat hippocampus.
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PMID:Influence of immobilization stress on the levels of CaMKII and phospho-CaMKII in the rat hippocampus. 1512 74

Because stress represents a major precipitating event for psychiatric disorders, it is important to identify molecular mechanisms that may be altered in vulnerable individuals when exposed to stress. Here, we studied GluR-A(-/-) mice, animals with compromised AMPA receptor signaling, and characterized by a schizophrenic as well as depressive phenotype to investigate changes occurring in response to an acute stress. Wild-type and GluR-A(-/-) mice were exposed to a single immobilization stress and sacrificed immediately after the end of the stress for the analysis of activity regulated genes and of glutamatergic synapse responsiveness. The acute stress produced a marked increase in the hippocampal expression of Arc (activity-regulated cytoskeletal-associated protein) in GluR-A(-/-) , but not in wild-type mice, which was associated with a similar increase of phospho-CaMKII, a partner in the action of Arc. When looking at the glutamatergic response to stress in wild-type animals, we found that stress increased GluR-A phosphorylation on serine831, an effect that was paralleled by a significant increase of the phosphorylation of the main NMDA receptor subunits, that is, NR-1 and NR-2B. Conversely, the stress-induced modulation of NMDA receptor subunits was not observed in GluR-A(-/-) mice. We suggest that enhanced stress responsiveness in GluR-A(-/-) mice may be due, at least in part, to their inability to activate NMDA-mediated glutamatergic neurotransmission, suggesting that the integrity of AMPA/NMDA receptor function may be important for successful coping under stressful conditions.
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PMID:AMPA GluR-A receptor subunit mediates hippocampal responsiveness in mice exposed to stress. 2057 99

The plasticity of excitatory synapses is an essential brain process involved in cognitive functions, and dysfunctions of such adaptations have been linked to psychiatric disorders such as depression. Although the intracellular cascades that are altered in models of depression and stress-related disorders have been under considerable scrutiny, the molecular interplay between antidepressants and glutamatergic signaling remains elusive. Using a combination of electrophysiological and single nanoparticle tracking approaches, we here report that the cognitive enhancer and antidepressant tianeptine (S 1574, [3-chloro-6-methyl-5,5-dioxo-6,11-dihydro-(c,f)-dibenzo-(1,2-thiazepine)-11-yl) amino]-7 heptanoic acid, sodium salt) favors synaptic plasticity in hippocampal neurons both under basal conditions and after acute stress. Strikingly, tianeptine rapidly reduces the surface diffusion of AMPA receptor (AMPAR) through a Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent mechanism that enhances the binding of AMPAR auxiliary subunit stargazin with PSD-95. This prevents corticosterone-induced AMPAR surface dispersal and restores long-term potentiation of acutely stressed mice. Collectively, these data provide the first evidence that a therapeutically used drug targets the surface diffusion of AMPAR through a CaMKII-stargazin-PSD-95 pathway, to promote long-term synaptic plasticity.
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PMID:Regulation of AMPA receptor surface trafficking and synaptic plasticity by a cognitive enhancer and antidepressant molecule. 2273 25