Induced neuronal expression of class I major histocompatibility complex mRNA in acute and chronic inflammation models

Foster, Jane A.; Quan, Ning; Stern, Edra L; Kristensson, Krister; Herkenham, Miles

doi:10.1016/s0165-5728(02)00258-8

Cited by 50 publications

(34 citation statements)

References 55 publications

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“…MHCI levels are dynamic during development and are regulated by activity (3), and thus our results suggest a mechanism whereby changes in MHCI levels could link developmental stage and synaptic activity to physiological changes in the rules governing synaptic plasticity in vivo. Neuronal MHCI levels are also increased during inflammation (44), seizures (3), injury (45), and aging (46). By limiting NMDAR function, higher levels of MHCI under these conditions could prevent runaway potentiation and act as an endogenous neuroprotective against NMDAR-mediated excitotoxicity.…”

Section: Discussionmentioning

confidence: 99%

MHC class I modulates NMDA receptor function and AMPA receptor trafficking

Fourgeaud¹,

Davenport²,

Tyler

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Proteins of the major histocompatibility complex class I (MHCI) are known for their role in immunity and have recently been implicated in long-term plasticity of excitatory synaptic transmission. However, the mechanisms by which MHCI influences synaptic plasticity remain unknown. Here we show that endogenous MHCI regulates synaptic responses mediated by NMDA-type glutamate receptors (NMDARs) in the mammalian central nervous system (CNS). The AMPA/NMDA ratio is decreased at MHCI-deficient hippocampal synapses, reflecting an increase in NMDAR-mediated currents. This enhanced NMDAR response is not associated with changes in the levels, subunit composition, or gross subcellular distribution of NMDARs. Increased NMDAR-mediated currents in MHCI-deficient neurons are associated with characteristic changes in AMPA receptor trafficking in response to NMDAR activation. Thus, endogenous MHCI tonically inhibits NMDAR function and controls downstream NMDAR-induced AMPA receptor trafficking during the expression of plasticity.immune | GluR | hippocampus P roteins of the major histocompatibility complex class I (MHCI) are best known for their role in adaptive immunity, but several lines of evidence suggest they also have nonimmune functions in neurons (1, 2). MHCI is expressed by healthy neurons in the developing and adult CNS (3-7). Neuronal MHCI mRNA levels are dynamic during development and are regulated by electrical activity (3, 4) and by the cAMP-response element-binding protein (CREB) (8). MHCI protein is enriched in synaptic fractions (4) and is detected in hippocampal dendritic spines, where it colocalizes with PSD-95 (9).Studies in mice genetically deficient for cell-surface MHCI (β2m −/− TAP −/− mice) suggest a role for MHCI in activity-dependent plasticity. In MHCI-deficient mice, NMDA receptor (NMDAR)-dependent hippocampal long-term potentiation (LTP) is enhanced, whereas long-term depression (LTD) is abolished (4). Although the mechanisms by which MHCI mediates immune signaling have been relatively well characterized, nothing is known about how MHCI contributes to NMDAR-dependent plasticity in vitro or in vivo.In the adult hippocampus, plasticity induced by activation of NMDARs is expressed as changes in the trafficking and function of AMPA receptors (AMPARs) (10-13). In current models, the magnitude and kinetics of NMDAR activation determine whether potentiation or depression is induced, with large, transient NMDAR activation causing LTP and smaller, longer-lasting activation causing LTD (14, 15). Therefore, to better understand the role of endogenous MHCI in the induction or expression of synaptic plasticity, we examined the levels, distribution, trafficking, and function of AMPA-and NMDA-type receptors in MHCI-deficient hippocampal neurons.The current experiments reveal an unexpected role for postsynaptic MHCI in controlling NMDAR function. Loss of MHCI causes a drop in the AMPA/NMDA ratio and an enhancement of NMDAR-mediated responses at CA3-CA1 synapses. This enhancement cannot be attributed to changes in th...

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Section: Discussionmentioning

confidence: 99%

MHC class I modulates NMDA receptor function and AMPA receptor trafficking

Fourgeaud¹,

Davenport²,

Tyler

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Levels of IL-1␤, TNF-␣, proopiomelanocortin, and neuropeptide Y (NPY) mRNAs were assessed by in situ hybridizations using 35S-labeled RNA probes on frozen brain sections, as described previously (9). Brains were rapidly frozen in 2-methylbutane at Ϫ60°C, and stored at Ϫ70°C.…”

Section: Methodsmentioning

confidence: 99%

Role of gut-brain axis in persistent abnormal feeding behavior in mice following eradication of Helicobacter pylori infection

Berčík

Verdú²,

Foster³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Here, we investigate the role of the gut-brain axis in gastric dysfunction during and after chronic H. pylori infection. Control and chronically H. pylori-infected Balb/c mice were studied before and 2 mo after bacterial eradication. Gastric motility and emptying were investigated using videofluoroscopy image analysis. Gastric mechanical viscerosensitivity was assessed by cardioautonomic responses to distension. Feeding patterns were recorded by a computer-assisted system. Plasma leptin, ghrelin, and CCK levels were measured using ELISA. IL-1␤, TNF-␣, proopiomelanocortin (POMC), and neuropeptide Y mRNAs were assessed by in situ hybridizations on frozen brain sections. Gastric inflammation was assessed by histology and immunohistochemistry. As shown previously, H. pylori-infected mice ate more frequently than controls but consumed less food per bout, maintaining normal body weight. Abnormal feeding behavior was accompanied by elevated plasma ghrelin and postprandial CCK, higher TNF-␣ (median eminence), and lower POMC (arcuate nucleus) mRNA. Infected mice displayed delayed gastric emptying and visceral hypersensitivity. Eradication therapy normalized gastric emptying and improved gastric sensitivity but had no effect on eating behavior. This was accompanied by persistently increased TNF-␣ in the brain and gastric CD3 ϩ T-cell counts. In conclusion, chronic H. pylori infection in mice alters gastric emptying and mechanosensitivity, which improve after bacterial eradication. A feeding pattern reminiscent of early satiety persists after H. pylori eradication and is accompanied by increased TNF-␣ in the brain. The results support a role for altered gut-brain pathways in the maintenance of postinfective gut dysfunction.inflammation; gut-brain axis; gastric emptying; visceral sensitivity FUNCTIONAL GI DISORDERS SUCH as irritable bowel disease (IBS) and functional dyspepsia (FD) have traditionally been viewed as psychosomatic. The concept that previous infection can trigger the development of functional GI disease is now accepted. A large cohort study identified bacterial gastroenteritis as the most significant risk factor identified to date for the development of IBS (24). IBS symptoms have been reported to develop in a significant proportion of subjects with documented Campylobacter, Salmonella, E. coli, or Shigella infection (12,32,37). A similar case has been also made for functional dyspepsia (18,33). These studies were restricted to acute enteric infections.Accumulating evidence suggests that changes in the bacterial content in the gut can affect the central nervous system (CNS) (10, 13). Most of these studies have dealt with the effect of acute infection and early CNS changes that occurred before the onset of the inflammatory response to the infection. The effect of chronic GI infection and inflammation on the CNS has not yet been investigated. Previous studies suggested that vagal sensory afferents are responsible for the rapid changes that occur in the brain within hours of a GI infection (13). However, multiple...

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“…Neurons express MHC Class I protein during acute inflammation and changes in electrical activity, e.g. after axotomy, cytokine treatment and viral infection (Corriveau et al, 1998;Foster et al, 2002;Lind˚a et al, 1998;Maehlen et al, 1988;Neumann, 2001;Schultzberg et al, 1989;Thams et al, 2008). The expression of MHC Class I in neurons seems to be more strictly regulated than the expression by microglia, the latter often classified as the best antigen-presenting cells in the nervous system (Neumann, 2001).…”

Section: Introductionmentioning

confidence: 99%

Evidence of hypothalamic degeneration in the anorectic anx/anx mouse

Nilsson

Thams

Lindfors

et al. 2010

Glia

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Mice homozygous for the anorexia (anx) mutation are characterized by poor food intake and death by three to five weeks after birth. By P21 these mice display lower density of hypothalamic neuropeptides, including Agouti gene-related protein (AGRP). The AGRP/neuropeptide Y (NPY) system of the anx/anx mice develops normally until postnatal day (P) 12, then the normal increase in fiber density ceases, in some areas even distinctly decreases. This overlaps with activation of microglia, indicating an inflammatory and/or degenerative process. Here we studied, by in situ hybridization and immunohistochemistry (IHC), the expression of major histocompatibility complex (MHC) class I-related molecules and markers for cellular reactivity in hypothalamus of anx/anx mice. MHC class I transcript and -related proteins were found in arcuate nucleus (Arc), presumably both in neurons and glia, the latter also in areas innervated by AGRP (NPY) neurons. In the anx/anx hypothalamus, using TUNEL labeling, significantly higher number of apoptotic cells were found compared with +/+ mice, and active caspase 6 immunoreactivity was detected in degenerating NPY-fibers as well as signs of "microglia-associated cell death". In addition, Y1 receptor-labeled processes and soma of pro-opiomelanocortin (POMC) neurons, were markedly decreased at P21. These results support the hypothesis of degeneration of hypothalamic arcuate neuron populations in the anx/anx mice, whereby the AGRP system may be first affected, the changes in the POMC system being secondary in this process.

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Induced neuronal expression of class I major histocompatibility complex mRNA in acute and chronic inflammation models

Cited by 50 publications

References 55 publications

MHC class I modulates NMDA receptor function and AMPA receptor trafficking

MHC class I modulates NMDA receptor function and AMPA receptor trafficking

Role of gut-brain axis in persistent abnormal feeding behavior in mice following eradication of Helicobacter pylori infection

Evidence of hypothalamic degeneration in the anorectic anx/anx mouse

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