Chronic neuroinflammation impacts the recruitment of adult-born neurons into behaviorally relevant hippocampal networks - PubMed (original) (raw)

Chronic neuroinflammation impacts the recruitment of adult-born neurons into behaviorally relevant hippocampal networks

Karim Belarbi et al. Brain Behav Immun. 2012 Jan.

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.

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Figures

Fig. 1

Fig. 1

Impact of chronic neuroinflammation on neurogenesis and the migration of adult-born neurons two months after LPS infusion terminated. (A) Numbers of activated microglia (OX-6 immunoreactive) within the DG of aCSF- and LPS-treated rats (***p=0.0001 vs. aCSF). (B) The number of BrdU-labeled neurons in the DG enclosed blade did not significantly differ between aCSF-treated and LPS-treated animals (p=0.7577). (C) Index of migration calculated as im = m / w × 100, “m” is the distance between the center of the nucleus and the subgranular zone; “w” is the width of the granule cell layer. (D) The index of migration was higher in LPS-treated rats than in aCSF-treated rats (*p=0.0192).

Fig. 2

Fig. 2

Impact of chronic neuroinflammation on the expression of behaviorally-induced Arc in existing and adult-born neurons measured two months after LPS infusion terminated. (A) Representative image of double immunofluorescence staining for activated microglia (OX-6 positive) (blue) and Arc protein (red) in the DG of an LPS-treated animal. Nuclei were counterstained with SYTOX Green. (B) There was a significant correlation between the density of activated microglia and the percentage increase of exploration-induced Arc in the DG of LPS-treated rats, above that of aCSF-treated rats (r=0.7063; p=0.0334). (C) Triple immunofluorescence staining for NeuN (Blue), BrdU (green) and Arc (red). The white arrow points to a triple-labeled cell (scale = 10 μm). (D) In aCSF-treated rats, the percentage of BrdU-labeled neurons expressing Arc was higher than the percentage of neurons that expressed Arc in the already existing population of granule cells (**p<0.01). In LPS-treated animals, the percentage of BrdU-labeled neurons expressing Arc was not significantly different than that of the already existing population of neurons. The proportion of BrdU-labeled neurons expressing Arc was significantly lower in LPS-treated animals than in aCSF-treated animals (##p<0.01).

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