Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 43, Issue -, Pages 149-158Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2014.07.020
Keywords
Interleukin 6; Anti-inflammatory reflex; Lipopolysaccharide; GABA; Vagal nerve stimulation
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Funding
- NINDS NIH HHS [R01 NS040408] Funding Source: Medline
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The ratio between synaptic inhibition and excitation (sl/E) is a critical factor in the pathophysiology of neuropsychiatric disease. We recently described a stress-induced interleukin-6 dependent mechanism leading to a decrease in sl/E in the rodent temporal cortex. The aim of the present study was to determine whether a similar mechanism takes place in the prefrontal cortex, and to elaborate strategies to prevent or attenuate it. We used aseptic inflammation (single acute injections of lipopolysaccharide, LPS, 10 mg/kg) as stress model, and patch-clamp recording on a prefrontal cortical slice preparation from wild-type rat and mice, as well as from transgenic mice in which the inhibitor of IL-6 trans-signaling sgp130Fc was produced in a brain-specific fashion (sgp130Fc mice). The anti-inflammatory reflex was activated either by vagal nerve stimulation or peripheral administration of the nicotinic alpha(7) receptor agonist PHA543613. We found that the IL-6-dependent reduction in prefrontal cortex synaptic inhibition was blocked in sgp130Fc mice, or - in wild-type animals - upon application sgp130Fc. Similar results were obtained by activating the anti-inflammatory reflex - a neural circuit regulating peripheral immune response - by stimulation of the vagal nerve or through peripheral administration of the alpha(7) nicotinic receptor agonist PHA543613. Our results indicate that the prefrontal cortex is an important potential target of IL-6 mediated transsignaling, and suggest a potential new avenue in the treatment of a large class of hyperexcitable neuropsychiatric conditions, including epilepsy, schizophrenic psychoses, anxiety disorders, autism spectrum disorders, and depression. (C) 2014 Published by Elsevier Inc.
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