title: Chronic neuroinflammation impacts the recruitment of adult-born neurons into behaviorally relevant hippocampal networks.
abstract: Growing evidence suggests that adult-born granule cells integrate into hippocampal networks and are required for proper cognitive function. Although neuroinflammation is involved in many disorders associated with cognitive impairment, it remains unknown whether it impacts the recruitment of adult-born neurons into behaviorally relevant hippocampal networks. Under similar behavioral conditions, exploration-induced expression of the immediate-early gene Arc in hippocampal cells has been linked to cellular activity observed by electrophysiological recording. By detecting exploration-induced Arc protein expression, we investigated whether neuroinflammation alters the recruitment of adult-born neurons into behaviorally relevant hippocampal networks. Neuroinflammation was induced in rats by intra-cerebroventricular infusion of lipopolysaccharide for 28 days. Animals received bromodeoxyuridine injections starting on day 29 (5 days) and were euthanized two months later. Persistent lipopolysaccharide-induced neuroinflammation was reliably detected by microglial activation in the hippocampus. Neuroinflammation did not impact the number of adult-born neurons but did alter their migration pattern through the granule cell layer. There was a positive correlation between the density of activated microglia and alterations in the fraction of existing granule neurons expressing Arc, suggesting that neuroinflammation induced a long-term disruption of hippocampal network activity. The proportion of adult-born neurons expressing behaviorally induced Arc was significantly lower in lipopolysaccharide-treated rats than in controls. This observation supports the fact that neuroinflammation significantly impacts adult-born neurons recruitment into hippocampal networks encoding spatial information.
authors.affiliation: Brain and Spinal Injury Center, University of California, San Francisco, CA, USA.
authors.forename: Karim
authors.initials: K
authors.lastname: Belarbi
authors.forename: Carla
authors.initials: C
authors.lastname: Arellano
authors.forename: Ryan
authors.initials: R
authors.lastname: Ferguson
authors.forename: Timothy
authors.initials: T
authors.lastname: Jopson
authors.forename: Susanna
authors.initials: S
authors.lastname: Rosi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000473:pathology; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology; D002908:Chronic Disease; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects; D009415:Nerve Net / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009443:Neuritis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000276:immunology* / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D011999:Recruitment, Neurophysiological / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein