Systemic administration of interleukin‐1β activates select populations of central amygdala afferents

Abstract

The central nucleus of the amygdala (CeA) is activated robustly by an immune challenge such as the systemic administration of the proinflammatory cytokine interleukin-1␤ (IL-1␤). Because IL-1␤ is not believed to cross the blood-brain barrier in any significant amount, it is likely that IL-1␤ elicits CeA cell recruitment by means of activation of afferents to the CeA. However, although many studies have investigated the origins of afferent inputs to the CeA, we do not know which of these also respond to IL-1␤. Therefore, to identify candidate neurons responsible for the recruitment of CeA cells by an immune challenge, we iontophoretically deposited a retrograde tracer, cholera toxin b-subunit (CTb), into the CeA of rats 7 days before systemic delivery of IL-1␤ (1 g/kg, i.a.). By using combined immunohistochemistry, we then quantified the number of Fos-positive CTb cells in six major regions known to innervate the CeA. These included the medial prefrontal cortex, paraventricular thalamus (PVT), ventral tegmental area, parabrachial nucleus (PB), nucleus tractus solitarius, and ventrolateral medulla. Our results show that after deposit of CTb into the CeA, the majority of double-labeled cells were located in the PB and the PVT, suggesting that CeA cell activation by systemic IL-1␤ is likely to arise predominantly from cell bodies located in these regions. These findings may have significant implications in determining the central pathways involved in generating acute central responses to a systemic immune challenge.

Bed Nucleus of the Stria Terminalis Subregions Differentially Regulate Hypothalamic–Pituitary–Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

“…Thus, CRHexpressing central amygdalar neurons (Champagne et al, 1998) may activate the HPA axis by connecting with the dorsomedial/ fusiform BST nuclei (Prewitt and Herman, 1998) that express CRH/Glu to form an excitatory, bisynaptic CRH-CRH/Glu signal to the PVNmp (Paull and Gibbs, 1983;Silverman et al, 1989). Alternatively, the central nucleus of the amygdala may stimulate HPA activation (Van de Kar et al, 1991;Buller and Day, 2002) via GABA-GABA transsynaptic disinhibition (Cullinan et al, 1993) (Fig. 11).…”

Neurobiology of inflammation-associated anorexia

“…NTS neurons activated in response to inflammation send projections to the lateral parabrachial nucleus (lPB), bed nucleus of the stria terminalis (BST), central amygdala (CeA) and paraventricular nucleus of the hypothalamus (PVN) (Ericsson et al, 1994; Tkacs and Li, 1999; Buller and Day, 2002; Crane et al, 2003; Gaykema et al, 2007) (Figure 1). The exact role of the aforementioned structures in feeding behavior remains understudied, however, it is known that these structures all receive visceral- and gustatory-related information and are, individually or collectively, implicated in hypophagic behaviors such as stress-induced anorexia (Koob, 1999), satiety/aversion (Reilly and Trifunovic, 2000; Sclafani et al, 2001; Ferreira et al, 2006; Becskei et al, 2007), food avoidance and preference (Kelley et al, 2003; Ferreira et al, 2006).…”

Theoretical aspects of autism: biomarkers—a review

“…The activation of brain microglia can occur by way of macrophage/lymphocyte interactions and by IL-1β (a cytokine) infiltration into the brain, demonstrated by the effect of systemic infection on cognitive decline in Alzheimer's disease (Holmes et al, 2003). The amygdala is regarded as a critical limbic site for integration and processing of autonomic, endocrine, and behavior-related information (Davis et al, 1994;Buller and Day, 2002). Considering the available information, a unifying concept for autism would be to measure glutamate and immune cytokines to characterize autism.…”