Article

Belarbi K, Arellano C, Ferguson R, Jopson T, Rosi S. Chronic neuroinflammation impacts the recruitment of adult-born neurons into behaviorally relevant hippocampal networks. Brain Behav Immun 26: 18-23

Brain and Spinal Injury Center, University of California, San Francisco, CA, USA.
Brain Behavior and Immunity (Impact Factor: 5.89). 07/2011; 26(1):18-23. DOI: 10.1016/j.bbi.2011.07.225
Source: PubMed

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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Available from: Susanna Rosi, Mar 26, 2014
    • "In addition, peripheral LPS injection to rats in early life had no effect on neurogenesis in later life, but a second LPS challenge in adulthood impaired neurogenesis (Dinel et al., 2014). However, it has also been shown that chronic intracerebroventricular (i.c.v.) administration of LPS to adult rats for 28 days did not affect the number of newly born neurons but only more subtly altered their migration pattern through the GCL and decreased the expression of the behaviourally-induced immediate early gene arc (Belarbi et al., 2012). While these data collectively demonstrate a detrimental effect of inflammation on hippocampal neurogenesis, the degree of damage may depend upon the dose, route and duration of exposure to LPS, and the time during the lifespan at which it is administered. "
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    ABSTRACT: Adult hippocampal neurogenesis is believed to be integral for certain forms of learning and memory. Dysregulation of hippocampal neurogenesis has been shown to be an important mechanism underlying the cognitive impairment associated with normal aging, as well as the cognitive deficits evident in preclinical models of Alzheimer's disease and other neurodegenerative diseases. Neuroinflammation is a significant pathological feature of these conditions; it contributes to the observed cognitive decline, and recent evidence demonstrates that it also negatively affects hippocampal neurogenesis. Conversely, during the past twenty years, it has been robustly shown that exercise is a potent inducer of hippocampal neurogenesis, and it is believed that the positive beneficial effect of exercise on cognitive function is likely due to its pro-neurogenic effects. However, the interplay between exercise- and neuroinflammatory-induced changes in hippocampal neurogenesis and associated cognitive function has only recently begun to receive attention. Here we review the current literature on exercise-induced effects on hippocampal neurogenesis, cognitive function and neuroinflammation, and consider exercise as a potential pro-neurogenic and anti-inflammatory intervention for cognition.
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    • "Although electrophysiological or optogenetics approaches will be needed to demonstrate the newborn granule neuron- CA2 functional connectivity and whether these connections could affect hippocampal behavior, these experiments provide further confirmation of their existence and possibility of function. Indeed, our data suggest that both neuroprotective and deleterious stimuli modulate this connection simultaneously to both AHN and hippocampal-dependent memory regulation (Belarbi et al., 2012; Cassilhas et al., 2012). Our findings reveal a novel mechanism of hippocampal plasticity, which may have important functional and behavioral consequences. "
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    • "Conditions stimulating cell proliferation enhance the number of early postmitotic cells in the DG (Brandt et al., 2003), affecting mainly the septal part. Innate neuroinflammation due to experimental allergic encephalomyelitis (EAE) or lipopolysaccharide (LPS)-induced, enhance the proliferation of NPCs in DG (Ekdahl et al., 2003,2009; Das and Basu, 2008; Pluchino et al., 2008; Huehnchen et al., 2011; Voloboueva and Giffard, 2011; Belarbi et al., 2012; Giannakopoulou et al., 2013), being more intense in the septal DG. Although the exact molecular mechanisms that regulate NPCs proliferation and differentiation are largely unknown, several factors have been shown to affect DG neurogenesis. "
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