Identification and characterization of receptors for tumor necrosis factor-α in the brain

Kinouchi, Keiko; Brown, George P.; Pasternak, Gavril W.; Donner, David B.

doi:10.1016/0006-291x(91)92113-x

Cited by 172 publications

(67 citation statements)

References 7 publications

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“…Although it is conceivable that the timelimited nature of SERT activation in these experiments was a product of our methodology (ie these cytokines might induce more prolonged activation of SERT in vivo), it is tempting to consider that the brevity of this effect reflects the capability of time-limited cytokine exposure to induce short-term reductions in 5-HT availability. Both TNF-a and IL-1b mRNA and protein are known to be present in specific CNS neuronal populations (Breder et al, 1988(Breder et al, , 1993Ignatowski and Spengler, 1994;Ignatowski et al, 1997), and receptors for these cytokines have differential brain regional distributions (Farrar et al, 1987;Takao et al, 1990;Ban et al, 1991;Kinouchi et al, 1991;Cunningham et al, 1992). Brief local exposure to these cytokines results in both documented neuronal and behavioral effects.…”

Section: Discussionmentioning

confidence: 99%

The Proinflammatory Cytokines Interleukin-1beta and Tumor Necrosis Factor-Alpha Activate Serotonin Transporters

Zhu

Blakely

Hewlett

2006

Neuropsychopharmacol

482

317

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Proinflammatory cytokines and serotonergic homeostasis have both been implicated in the pathophysiology of major psychiatric disorders. We have demonstrated that activation of p38 mitogen-activated protein kinase (MAPK) induces a catalytic activation of the serotonin transporter (SERT) arising from a reduction in the SERT K m for 5-hydroxytryptamine (5-HT). As inflammatory cytokines can activate p38 MAPK, we hypothesized that they might also activate neuronal SERT. Indeed, Interleukin-1beta (IL-1b) and tumor necrosis factor alpha (TNF-a) stimulated serotonin uptake in both the rat embryonic raphe cell line, RN46A, and in mouse midbrain and striatal synaptosomes. In RN46A cells, IL-1b stimulated 5-HT uptake in a dose-and time-dependent manner, peaking in 20 min at 100 ng/ml. This was abolished by IL-1ra (20 ng/ml), an antagonist of the IL-1 receptor, and by SB203580 (5 mM), a p38 MAPK inhibitor. TNF-a also dose-and time-dependently stimulated 5-HT uptake that was only partially blocked by SB203580. Western blots showed that IL-1b and TNF-a activated p38 MAPK, in an SB203580-sensitive manner. IL-1b induced an SB203580-sensitive decrease in 5-HT K m with no significant change in V max . In contrast, TNF-a stimulation decreased 5-HT K m and increased SERT V max . SB203580 selectively blocked the TNF-a-induced change in SERT K m . In mouse midbrain and striatal synaptosomes, maximal stimulatory effects on 5-HT uptake occurred at lower concentrations (IL-1b, 10 ng/ml; TNF-a, 20 ng/ml), and over shorter incubation times (10 min). As with RN46A cells, the effects of IL-1b and TNF-a were completely (IL-1b) or partially (TNF-a) blocked by SB203580. These results provide the first evidence that proinflammatory cytokines can acutely regulate neuronal SERT activity via p38 MAPK-linked pathways.

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Section: Discussionmentioning

confidence: 99%

The Proinflammatory Cytokines Interleukin-1beta and Tumor Necrosis Factor-Alpha Activate Serotonin Transporters

Zhu

Blakely

Hewlett

2006

Neuropsychopharmacol

482

317

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“…Animal studies have identified TNF receptors in the murine brain and elaborate IL-1 nerve fibers within the hypothalamus of rats. Rat astrocytes have also been shown to produce of TNF in vivo (Lieberman et al, 1989;Kinouchi et al, 1991;Hill et al, 1996). Additional studies have implicated several cytokines, namely IL-1, 2,6 and granulocyte-macrophage CSF in hippocampal neurotransmitter modulation (Bianchi et al, 1998).…”

Section: Cellular Theoriesmentioning

confidence: 99%

Impaired cognitive function and mental performance in mild dehydration

2003

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Dehydration is a reliable predictor of impaired cognitive status. Objective data, using tests of cortical function, support the deterioration of mental performance in mildly dehydrated younger adults. Dehydration frequently results in delirium as a manifestation of cognitive dysfunction. Although, the occurrence of delirium suggests transient acute global cerebral dysfunction, cognitive impairment may not be completely reversible. Animal studies have identified neuronal mitochondrial damage and glutamate hypertransmission in dehydrated rats. Additional studies have identified an increase in cerebral nicotinamide adenine dinucleotide phosphate-diaphorase activity (nitric oxide synthase, NOS) with dehydration. Available evidence also implicates NOS as a neurotransmitter in long-term potentiation, rendering this a critical enzyme in facilitating learning and memory. With ageing, a reduction of NOS activity has been identified in the cortex and striatum of rats. The reduction of NOs synthase activity that occurs with ageing may blunt the rise that occurs with dehydration, and possibly interfere with memory processing and cognitive function. Dehydration has been shown to be a reliable predictor of increasing frailty, deteriorating mental performance and poor quality of life. Intervention models directed toward improving outcomes in dehydration must incorporate strategies to enhance prompt recognition of cognitive dysfunction.

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“…Neurons, akin to a number of other cell types, can express both p55 and p75 TNFRs (19,26,27); the genes for these receptors are located on human chromosomes 12 and 1, respectively. Based on amino acid sequencing, there is a 28% overall homology between p55 and p75 TNFRs.…”

Section: Knockout Of P75 Tnf Receptor Increases Human Neurondegeneratmentioning

confidence: 99%

“…These results were further supported by similar results obtained using anti-human p75 TNFR-neutralizing antibody, suggesting that p75 TNFR may play a critical role in the ability of neurons to respond to insults. In addition, treating human neurotypic cells with ASO in vitro has proven to be a useful technique to suppress specific gene expression and to enable study of the functional significance of the corresponding protein (24,25).Neurons, akin to a number of other cell types, can express both p55 and p75 TNFRs (19,26,27); the genes for these receptors are located on human chromosomes 12 and 1, respectively. Based on amino acid sequencing, there is a 28% overall homology between p55 and p75 TNFRs.…”

mentioning

confidence: 99%

Inhibition of p75 Tumor Necrosis Factor Receptor by Antisense Oligonucleotides Increases Hypoxic Injury and β-Amyloid Toxicity in Human Neuronal Cell Line

Shen

Shiosaki

1997

Journal of Biological Chemistry

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Recent evidence indicates that tumor necrosis factor-␣ (TNF-␣) is up-regulated following brain injury andin neurodegenerative disorders such as stroke, multiple sclerosis, Parkinson's disease, and Alzheimer's disease. TNF-␣ elicits its biological effects through two distinct TNF receptor (TNFR) subtypes: p55 TNFR (TNFR1) and p75 TNFR (TNFR2). Studies have demonstrated that the p55 TNFR contributes to cell death, whereas the role of the p75 TNFR in neuronal viability is unclear. To better understand the role of p75 TNFR, we treated human neuronal SH-SY5Y cells with phosphorothioate-modified antisense oligonucleotides (ASO) for p75 TNFR and established that ASO inhibited p75 TNFR expression. Treatment of SH-SY5Y cells with ASO alone did not affect cell viability, whereas treatment with both ASO and human TNF-␣ significantly increased cell death relative to treatment with TNF-␣ alone. Moreover, addition of ASO significantly increased the level of cell injury observed following hypoxic conditions or exposure of ␤-amyloid peptide. These results indicate that inhibition of p75 TNFR using ASO increases the vulnerability of neurotypic cells to insults and suggest that the p75 TNFR may not be required for normal neuronal cell viability but rather plays a protective role following injury.Tumor necrosis factor-␣ (TNF-␣), 1 an inflammatory mediator, is recently reported to be up-regulated following brain trauma (1, 2) and ischemic injury (3, 4), and in multiple sclerosis (5, 6), Parkinson's disease (7), and Alzheimer's disease (8). Studies have shown that TNF-␣ can elicit either a trophic or toxic effect, which is dependent on the target cell type. For example, TNF-␣ is toxic to human oligodendrocytes (9) and neuronal cells (10, 11), but it is trophic to rat hippocampal neurons (12). Since TNF-␣ elicits its biological effects through activation of two distinct receptors, p55 TNFR and p75 TNFR, both of which have been cloned (13-15), we hypothesized that the distinct TNF receptor subtypes might contribute to the multiple biological functions of TNF-␣. Reports indicate that the p55 TNFR may contribute to cell death (16), whereas the role of the p75 TNFR in neuronal cell function is not clear. Here we show that inhibition of p75 TNFR by antisense oligonucleotides (ASO) increased the magnitude of neuronal cell death induced by TNF-␣, hypoxic injury or ␤-amyloid peptide (A␤) as measured by lactate dehydrogenase (LDH) release. This novel finding provides evidence that the p75 TNFR might play a protective role following neuronal insult. EXPERIMENTAL PROCEDURESCell Cultures-Human neuronal-like cells, SH-SY5Y, were cultured in a 1:1 ratio of minimum Eagle's medium/F-12 medium, 15% fetal calf serum (Life Technologies, Inc.), and 10 M retinoic acid (RA, Sigma). The cells were seeded at 25,000 cells/well in a 24-well plate for cytotoxicity assays or 3 ϫ 10 6 cells in Petri dishes for radioimmunoprecipitation study. The medium was replaced every 3 days. Treatments were given to the cells in serum-free medium with 1:100 N2-supplement (Li...

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Identification and characterization of receptors for tumor necrosis factor-α in the brain

Cited by 172 publications

References 7 publications

The Proinflammatory Cytokines Interleukin-1beta and Tumor Necrosis Factor-Alpha Activate Serotonin Transporters

The Proinflammatory Cytokines Interleukin-1beta and Tumor Necrosis Factor-Alpha Activate Serotonin Transporters

Impaired cognitive function and mental performance in mild dehydration

Inhibition of p75 Tumor Necrosis Factor Receptor by Antisense Oligonucleotides Increases Hypoxic Injury and β-Amyloid Toxicity in Human Neuronal Cell Line

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