Evidence for Altered Control of Hypothalamic CRF in Immune‐Mediated Diseasesa

Harbuz, Michael S.; Jessop, David S.; Chowdrey, Hardial S.; Blackwell, J. M.; Larsen, Philip J.; Lightman, Stafford L.

doi:10.1111/j.1749-6632.1995.tb44701.x

Cited by 33 publications

(21 citation statements)

References 35 publications

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“…Similarly in the present study, we have noted that the Nramp1 mutant mice had reduced CRH mRNA associated with infectious disease susceptibility and behavioural stress responses. Although we do not know whether the responses in rats come under Nramp1 control, these data provide further evidence for the important protective role of the HPA axis in response to infection and disease and support accumulating evidence of the role of CRH in mediating these effects [53-57]. …”

Section: Discussionsupporting

confidence: 72%

Nramp1 is expressed in neurons and is associated with behavioural and immune responses to stress

et al. 2001

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The gene Nramp1 encoding the natural resistance-associated macrophage protein (Nramp1) influences susceptibility to intracellular infections and autoimmune diseases, and the humoral response to stress. Nramp1 functions as a proton/divalent cation antiporter in the membranes of late endosomes/lysosomes, regulating cytoplasmic iron levels in macrophages. The Drosophila homologue of Nramp1 is expressed in sensory neurons and macrophages, and influences taste behaviour directly through divalent cation transport. Here we demonstrate that murine Nramp1 is also expressed on neurons as well as microglial cells in the brain and influences the behavioural response to stress, hypothalamus-pituitary-adrenal (HPA) axis activation and mortality following Toxoplasma gondii infection in control and prestressed mice. We hypothesise that, although differences in HPA activation translate into differences in adrenal enlargement and basal circulating corticosterone levels, the primary influence of Nramp1 is at the level of the neuronal response to stress. These results provide new insight into the possible roles of divalent cation transporters of the Nramp gene family in regulating metal ion homeostasis in the brain and its pathological implications.

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Section: Discussionsupporting

confidence: 72%

Nramp1 is expressed in neurons and is associated with behavioural and immune responses to stress

et al. 2001

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“…4b). In chronic stress, SP decreases CRF mRNA in the PVN and increases plasma ACTH and corticosterone levels as a consequence of increased AVP activity in the pituitary gland [5]. In contrast to AA, EAE did not increase AVP in the ME, thus explaining the lower plasma ACTH and corticosterone levels in the treated groups.…”

Section: Discussionmentioning

confidence: 74%

“…In this same stress model, there is an increase in arginine vasopressin (AVP) levels in the median eminence (ME) [2] and in AVP mRNA in corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) [4]. In contrast, CRF mRNA levels decrease in response to repeated stimulation [5]. This effect is dependent on the action of substance P (SP) in parvocellular neurons of the PVN [8] in vivo [6] and in vitro [7].…”

Section: Introductionmentioning

confidence: 91%

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Hypothalamic Response to Experimental Allergic Encephalomyelitis: Role of Substance P

Ruocco

Fernandes²,

Namer³

et al. 2003

Neuroimmunomodulation

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Adjuvant-induced arthritis (AA) is thought to be a model for experimental chronic stress that has as main features decreased adrenocorticotropin hormone (ACTH) plasma levels and a rise in median eminence content of arginine vasopressin (AVP) due to the activity of substance P. In experimental allergic encephalomyelitis (EAE), another chronic stress model, the role of substance P action is not clear. In this paper we tried to clarify the role of substance P in Lewis rats, which are susceptible to this disease. EAE was induced using myelin basic protein plus complete Freund’s adjuvant injected into the hind limbs. One day later injections of an antagonist to substance P (RP 67580), saline, and substance P were administered daily for 12–14 days through a stainless steel cannula into the lateral ventricle of the brain, and then the rats were killed. The rats were divided into groups of controls, sham, diseased controls (no intracerebroventricular injections) and EAE (injected intracerebroventricularly). Plasma was used for the quantification of ACTH and corticosterone but not AVP which was assayed in hypothalamic median eminence extracts. In noninjected diseased rats the plasma levels of ACTH and corticosterone were significantly higher than in noninjected control rats, whereas the AVP concentrations in the median eminence were unchanged. The substance P antagonist did not affect the levels of these hormones in plasma or the median eminence. Substance P decreased the plasma levels of ACTH and corticosterone but did not increase the median eminence content of vasopressin. Administration of the antagonist 30 min before an equivalent dose of substance P increased the plasma levels of the two hormones, but did not change the content of AVP. Based on the lack of response to the antagonist RP 67580 we suggest that the substance P has different roles in EAE and AA at least in the later stages of EAE (after 11 days of immunization).

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“…Changes in hypothalamic CRH also occur as a result of negative feedback regulation by stressinduced circulating glucocorticoids. For this reason, hypothalamic CRH declines on day 14 after the onset of chronic autoimmune CFA-induced arthritis (22).…”

Section: Figurementioning

confidence: 99%

Series Introduction: The immuno-neuroendocrine interface

Melmed¹

2001

J. Clin. Invest.

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Evidence for Altered Control of Hypothalamic CRF in Immune‐Mediated Diseasesa

Cited by 33 publications

References 35 publications

Nramp1 is expressed in neurons and is associated with behavioural and immune responses to stress

Nramp1 is expressed in neurons and is associated with behavioural and immune responses to stress

Hypothalamic Response to Experimental Allergic Encephalomyelitis: Role of Substance P

Series Introduction: The immuno-neuroendocrine interface

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