title: Activation of the anti-inflammatory reflex blocks lipopolysaccharide-induced decrease in synaptic inhibition in the temporal cortex of the rat.
abstract: Stress is a potential trigger for a number of neuropsychiatric conditions, including anxiety syndromes and schizophrenic psychoses. The temporal neocortex is a stress-sensitive area involved in the development of such conditions. We have recently shown that aseptic inflammation and mild electric shock shift the balance between synaptic excitation and synaptic inhibition in favor of the former in this brain area (Garcia-Oscos et al., 2012), as well as in the prefrontal cortex (Garcia-Oscos et al., 2014). Given the potential clinical importance of this phenomenon in the etiology of hyperexcitable neuropsychiatric illness, this study investigates whether inactivation of the peripheral immune system by the "anti-inflammatory reflex" would reduce the central response to aseptic inflammation. For a model of aseptic inflammation, this study used i.p. injections of the bacterial toxin lipopolysaccharide (LPS; 5 µM) and activated the anti-inflammatory reflex either pharmacologically by i.p. injections of the nicotinic α7 receptor agonist PHA543613 or physiologically through electrical stimulation of the left vagal nerve (VNS). Patch-clamp recording was used to monitor synaptic function. Recordings from LPS-injected Sprague Dawley rats show that activation of the anti-inflammatory reflex either pharmacologically or by VNS blocks or greatly reduces the LPS-induced decrease of the synaptic inhibitory-to-excitatory ratio and the saturation level of inhibitory current input-output curves. Given the ample variety of pharmacologically available α7 nicotinic receptor agonists as well as the relative safety of clinical VNS already approved by the FDA for the treatment of epilepsy and depression, our findings suggest a new therapeutic avenue in the treatment of stress-induced hyperexcitable conditions mediated by a decrease in synaptic inhibition in the temporal cortex.
authors: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, Texas; Department of Psychiatry, University of Texas Southwestern, Dallas, Texas.
authors: Francisco
authors: F
authors: Garcia-Oscos
authors: David
authors: D
authors: Peña
authors: Mohammad
authors: M
authors: Housini
authors: Derek
authors: D
authors: Cheng
authors: Diego
authors: D
authors: Lopez
authors: Roberto
authors: R
authors: Cuevas-Olguin
authors: Nadia
authors: N
authors: Saderi
authors: Roberto
authors: R
authors: Salgado Delgado
authors: Luis
authors: L
authors: Galindo Charles
authors: Humberto
authors: H
authors: Salgado Burgos
authors: Stefan
authors: S
authors: Rose-John
authors: Gonzalo
authors: G
authors: Flores
authors: Michael P
authors: MP
authors: Kilgard
authors: Marco
authors: M
authors: Atzori
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001703:Biophysics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use; D004195:Disease Models, Animal; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000628:therapy*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011812:Quinuclidines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013702:Temporal Lobe / Q000166:cytology / Q000187:drug effects*; D055536:Vagus Nerve Stimulation / Q000379:methods
chemical_list: D000893:Anti-Inflammatory Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008070:Lipopolysaccharides; C513163:N-(1-azabicyclo(2.2.2)oct-3-yl)furo(2,3-c)pyridine-5-carboxamide; D011812:Quinuclidines
keywords: GABA; PHA543613; VNS; nicotinic α7; vagal nerve stimulation