Bacterial Lipopolysaccharide‐Induced Changes in FOS Protein Expression in the Rat Brain: Correlation with Thermoregulatory Changes and Plasma Corticosterone

Hare, Alice; Clarke, Geoff; Tolchard, Stephen

doi:10.1111/j.1365-2826.1995.tb00716.x

Cited by 69 publications

(47 citation statements)

References 57 publications

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“…Previous results from our group have demonstrated that peripheral administration of this dose, from this particular batch of LPS is insufficient to cause elevations in CRH mRNA within the PVN, thus suggesting that its actions are mediated via central mechanisms in this study [21]. We have further noted a significant increase in both c-fos mRNA and Fos protein in the PVN and the A1 and A2 regions of the brainstem, confirming previous results concerning activation of the HPA axis and c-fos mRNA and Fos peptide following central injection of immune modulators [11, 29, 30]. We have now extended these observations to examine the role of glucocorticoid hormones in modulating these effects.…”

Section: Discussionsupporting

confidence: 78%

Central LPS-Induced <i>c-fos</i> Expression in the PVN and the A1/A2 Brainstem Noradrenergic Cell Groups Is Altered by Adrenalectomy

et al. 1999

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The A1 and A2 brainstem noradrenergic cell groups project to the hypothalamic paraventricular nucleus (PVN), which is involved in integrating the stress response. Bi-directional communication between the brain and immune system is well established, with both neuroendocrine and immune responses being activated by lipopolysaccharide (LPS). The mechanisms underlying such activation and differences between alternative routes of administration remain unclear. We examined activation of the PVN and A1/A2 cell groups, by assessing c-fos mRNA, or counting Fos-positive neurons in either the PVN or in brainstem A1/A2 cell groups 3 h after intracerebroventricular (i.c.v.) LPS, in control and adrenalectomized (ADX) rats. We also measured corticotropin-releasing hormone (CRH) mRNA in the PVN, and plasma corticosterone (CORT) levels. A group of ADX/CORT-replaced animals received i.c.v. LPS, and CRH mRNA and Fos peptide in the PVN were analysed. ADX increased CRH mRNA in the PVN, as did LPS, but no enhancement of this response was seen in LPS/ADX animals. C-fos mRNA also increased in both the PVN and the A2 cell group following LPS, but this response was potentiated by ADX. Fos peptide-containing cells increased in the PVN and A2 following LPS, and this change was amplified by ADX. Only 11.25% of Fos was found in DBH-positive (putative noradrenergic) neurons, suggesting activation of neurons containing other transmitters. ADX/LPS/CORT animals showed numbers of Fos neurons in the brainstem, and CRH mRNA levels in the PVN which were comparable to intact/LPS animals. Central LPS activates the hypothalamo-pituitary-adrenal axis, a process mediated partly by brainstem noradrenergic neurons, suggesting the involvement of afferent/efferent pathways within the brain. Peripheral administration of LPS involves activation of vagal inputs leading to the nucleus tractus solitarius. We suggest that centrally administered LPS activates the A2 cell group by a mechanism independent of the vagus. In the absence of CORT, despite the lack of a CRH mRNA response, an exaggerated c-fos and peptide response to LPS is observed, which is reversed following CORT pretreatment.

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Section: Discussionsupporting

confidence: 78%

Central LPS-Induced <i>c-fos</i> Expression in the PVN and the A1/A2 Brainstem Noradrenergic Cell Groups Is Altered by Adrenalectomy

et al. 1999

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“…Lesion of the locus coeruleus attenuates fever induced by LPS or intracerebroventricular PGE 2 in rats under a subneutral environmental temperature (23°C), but not under a neutral temperature (28°C) (2). These results suggest a modulatory role of locus coeruleus noradrenergic neurons in the central mechanism of fever, potentially through their projections to the POA, although the POA receives fewer noradrenergic projections from the locus coeruleus than those from A1 or A2 neurons (49).…”

Section: Central Processing Of Pyrogenic Signals For Fever Developmentmentioning

confidence: 59%

“…Noradrenergic inputs to the POA are likely provided by A1, A2, and locus coeruleus neurons in the pons and the medulla oblongata (184). These noradrenergic neuronal populations express c-Fos in response to LPS injection (49). Lesion of the locus coeruleus attenuates fever induced by LPS or intracerebroventricular PGE 2 in rats under a subneutral environmental temperature (23°C), but not under a neutral temperature (28°C) (2).…”

Section: Central Processing Of Pyrogenic Signals For Fever Developmentmentioning

confidence: 99%

Central circuitries for body temperature regulation and fever

Nakamura

2011

American Journal of Physiology-Regulatory, Integrative and Comp

433

394

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Nakamura K. Central circuitries for body temperature regulation and fever. Am J Physiol Regul Integr Comp Physiol 301: R1207-R1228, 2011. First published September 7, 2011 doi:10.1152/ajpregu.00109.2011.-Body temperature regulation is a fundamental homeostatic function that is governed by the central nervous system in homeothermic animals, including humans. The central thermoregulatory system also functions for host defense from invading pathogens by elevating body core temperature, a response known as fever. Thermoregulation and fever involve a variety of involuntary effector responses, and this review summarizes the current understandings of the central circuitry mechanisms that underlie nonshivering thermogenesis in brown adipose tissue, shivering thermogenesis in skeletal muscles, thermoregulatory cardiac regulation, heat-loss regulation through cutaneous vasomotion, and ACTH release. To defend thermal homeostasis from environmental thermal challenges, feedforward thermosensory information on environmental temperature sensed by skin thermoreceptors ascends through the spinal cord and lateral parabrachial nucleus to the preoptic area (POA). The POA also receives feedback signals from local thermosensitive neurons, as well as pyrogenic signals of prostaglandin E 2 produced in response to infection. These afferent signals are integrated and affect the activity of GABAergic inhibitory projection neurons descending from the POA to the dorsomedial hypothalamus (DMH) or to the rostral medullary raphe region (rMR). Attenuation of the descending inhibition by cooling or pyrogenic signals leads to disinhibition of thermogenic neurons in the DMH and sympathetic and somatic premotor neurons in the rMR, which then drive spinal motor output mechanisms to elicit thermogenesis, tachycardia, and cutaneous vasoconstriction. Warming signals enhance the descending inhibition from the POA to inhibit the motor outputs, resulting in cutaneous vasodilation and inhibited thermogenesis. This central thermoregulatory mechanism also functions for metabolic regulation and stress-induced hyperthermia.

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“…The expression of Fos protein in central autonomic nuclei by CCK and LPS exhibits a similar pattern (23,49). Both activate the central nucleus of the amygdala and hypothalamic structures, including the paraventricular nucleus (26,80,82), which has a role in temperature regulation (1,26). Furthermore, in the rat, CCK is found abundantly in the preoptic anterior hypothalamus (47), an area long known for thermoregulatory integration (5), which has connections with the nucleus of the solitary tract (NTS; 68).…”

Section: Discussionmentioning

confidence: 85%

CCK₂receptor nullification attenuates lipopolysaccharide-induced sickness behavior

Weiland¹,

Voudouris²,

Kent³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Weiland, Tracey J., Nicholas J. Voudouris, and Stephen Kent. CCK2 receptor nullification attenuates lipopolysaccharide-induced sickness behavior. Am J Physiol Regul Integr Comp Physiol 292: R112-R123, 2007. First published July 20, 2006; doi:10.1152/ajpregu.00156.2006.-Systemic infection produces a highly regulated set of responses such as fever, anorexia, adipsia, inactivity, and cachexia, collectively referred to as sickness behavior. Although the expression of sickness behavior requires immune-brain communication, the mechanisms by which peripheral cytokines signal the brain are unclear. Several mechanisms have been proposed for neuroimmune communication, including the interaction of cytokines with peripheral nerves. A critical role has been ascribed to the vagus nerve in mediating sickness behavior after intraperitoneally delivered immune activation, and converging evidence suggests that this communication may involve neurochemical intermediaries afferent and/or efferent to this nerve. Mice lacking functional CCK 2/gastrin receptors (CCK2KO) and wild-type (WT) controls were administered LPS (50, 500, or 2,500 g/kg; serotype 0111:B4; ip). Results indicate a role for CCK2 receptor activation in the initiation and maintenance of LPS-induced sickness behavior. Compared with WT controls, CCK 2KO mice were significantly less affected by LPS on measures of body temperature, activity, body weight, and food intake, with the magnitude of effects increasing with increasing LPS dose. Although activation of CCK 2 receptors at the level of the vagus nerve cannot be excluded, a possible role for these receptors in nonvagal routes of immune-brain communication is suggested. cholecystokinin; lipopolysaccharide; infection; vagus; fever THE GUT-BRAIN PEPTIDE, CCK, exhibits great potential as a neurochemical intermediary of vagus-to-brain signaling. CCK binds to CCK 1 and CCK 2 receptors; the former are primarily localized in peripheral organs and some discrete areas of the brain, whereas CCK 2 receptors are the predominant subtype in the brain (55). Both subtypes are present on the vagus nerve and vagal afferent connections, including the brainstem and hypothalamus (46,51). Thus the peripheral and central positioning of CCK receptors provides an anatomical basis for CCK to play a role in vagally mediated neuroimmune communication.A constellation of findings points to a role for CCK in immune regulation, including a protective function in septic shock induced by LPS (41, 42), a compound of the outer cell wall of Gram-negative bacteria (60). CCK induces monocyte chemotaxis both in vitro and in vivo (16, 65) and stimulates production of proinflammatory cytokines, TNF, IL-1␤, IL-6, and IL-8 (16). Peripheral administration of CCK induces a pattern of c-fos expression that is similar to that seen after administration of the immune activators, LPS, or IL-1␤ (19). Increases in plasma CCK have been reported in the rat after intraperitoneal IL-1␣ (18) or intravenous IL-1␤ (40). However, limitations in assay sensitivity and specificity r...

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Bacterial Lipopolysaccharide‐Induced Changes in FOS Protein Expression in the Rat Brain: Correlation with Thermoregulatory Changes and Plasma Corticosterone

Cited by 69 publications

References 57 publications

Central LPS-Induced <i>c-fos</i> Expression in the PVN and the A1/A2 Brainstem Noradrenergic Cell Groups Is Altered by Adrenalectomy

Central LPS-Induced <i>c-fos</i> Expression in the PVN and the A1/A2 Brainstem Noradrenergic Cell Groups Is Altered by Adrenalectomy

Central circuitries for body temperature regulation and fever

CCK₂receptor nullification attenuates lipopolysaccharide-induced sickness behavior

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Bacterial Lipopolysaccharide‐Induced Changes in FOS Protein Expression in the Rat Brain: Correlation with Thermoregulatory Changes and Plasma Corticosterone

Cited by 69 publications

References 57 publications

Central LPS-Induced <i>c-fos</i> Expression in the PVN and the A1/A2 Brainstem Noradrenergic Cell Groups Is Altered by Adrenalectomy

Central LPS-Induced <i>c-fos</i> Expression in the PVN and the A1/A2 Brainstem Noradrenergic Cell Groups Is Altered by Adrenalectomy

Central circuitries for body temperature regulation and fever

CCK2receptor nullification attenuates lipopolysaccharide-induced sickness behavior

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CCK₂receptor nullification attenuates lipopolysaccharide-induced sickness behavior