Document
Generically Dependent Continuant
RDF description of The stress-induced cytokine interleukin-6 decreases the inhibition/excitation ratio in the rat temporal cortex via trans-signaling - http://orbis.uaslp.mx/vivo/individual/scopus3134
Article
Deutsche Forschungsgemeinschaft, DFG: SFB877, SFB654, SFB841, A1
Information Content Entity
The stress-induced cytokine interleukin-6 decreases the inhibition/excitation ratio in the rat temporal cortex via trans-signaling
γ-aminobutyric acid (GABA); 2-Br-hexadecanoic acid; Brefeldin A; dynamin inhibitory peptide; foot-shock; gp130; interleukin-6 (IL-6); lipopolysaccharide (LPS); patch-clamp; PI3K/AKT; postsynaptic; rat; stress; temporal cortex; trans-signaling; wortmannin 2 br hexadecanoic acid; brefeldin A; dynamin; glycoprotein gp 130; interleukin 6; lipopolysaccharide; muscimol; palmitic acid; unclassified drug; wortmannin; animal experiment; animal model; article; cell migration; controlled study; electric shock; excitatory postsynaptic potential; footshock; GABAergic transmission; inhibitory postsynaptic potential; internalization; nonhuman; patch clamp; priority journal; rat; stress; temporal cortex; Androstadienes; Animals; Brefeldin A; Cytokine Receptor gp130; Disease Models, Animal; Drug Interactions; Electric Stimulation; Excitatory Postsynaptic Potentials; Inhibitory Postsynaptic Potentials; Interleukin-6; Lipopolysaccharides; Muscimol; Oligopeptides; Palmitates; Rats; Stress, Psychological; Temporal Lobe
Background: Although it is known that stress elevates the levels of pro-inflammatory cytokines and promotes hyper-excitable central conditions, a causal relationship between these two factors has not yet been identified. Recent studies suggest that increases in interleukin 6 (IL-6) levels are specifically associated with stress. We hypothesized that IL-6 acutely and directly induces cortical hyper-excitability by altering the balance between synaptic excitation and inhibition. Methods: We used patch-clamp to determine the effects of exogenous or endogenous IL-6 on electrically evoked postsynaptic currents on a cortical rat slice preparation. We used control subjects or animals systemically injected with lipopolysaccharide or subjected to electrical foot-shock as rat models of stress. Results: In control animals, IL-6 did not affect excitatory postsynaptic currents but selectively and reversibly reduced the amplitude of inhibitory postsynaptic currents with a postsynaptic effect. The IL-6-induced inhibitory postsynaptic currents decrease was inhibited by drugs interfering with receptor trafficking and/or internalization, including wortmannin, Brefeldin A, 2-Br-hexadecanoic acid, or dynamin peptide inhibitor. In both animal models, stress-induced decrease in synaptic inhibition/excitation ratio was prevented by prior intra-ventricular injection of an analog of the endogenous IL-6 trans-signaling blocker gp130. Conclusions: Our results suggest that stress-induced IL-6 shifts the balance between synaptic inhibition and excitation in favor of the latter, possibly by decreasing the density of functional γ-aminobutyric acid A receptors, accelerating their removal and/or decreasing their insertion rate from/to the plasma membrane. We speculate that this mechanism could contribute to stress-induced detrimental long-term increases in central excitability present in a variety of neurological and psychiatric conditions. © 2012 Society of Biological Psychiatry.
brefeldin A, 20350-15-6; muscimol, 2763-96-4; palmitic acid, 57-10-3; wortmannin, 19545-26-7; 2-bromopalmitate, 18263-25-7; Androstadienes; Brefeldin A, 20350-15-6; Cytokine Receptor gp130, 133483-10-0; Interleukin-6; Lipopolysaccharides; Muscimol, 2763-96-4; Oligopeptides; Palmitates; peptide P4; wortmannin, 19545-26-7