Proinflammatory cytokines and apoptosis following glutamate-induced excitotoxicity mediated by p38 MAPK in the hippocampus of neonatal rats

Chaparro-Huerta, V.; Rivera-Cervantes, M.C.; Flores-Soto, M.E.; Gómez‐Pinedo, Ulises; Beas‐Zárate, Carlos

doi:10.1016/j.jneuroim.2005.04.025

Cited by 80 publications

(64 citation statements)

References 34 publications

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“…Indeed, IL-6, IL-8, IL-1β, TNF-α, and MCP-1 levels are elevated in HD and are predicted to augment inflammatory signals in the brain. These factors could also contribute directly to neuronal dysfunction, as receptors for many of these molecules are expressed on neurons, some of which transduce proapoptotic signaling pathways (57,58). Consistent with this hypothesis, myeloid cells in mice mutant for the chemokine receptor Cx3cr1 are impaired in migration, leading to increased IL-1β levels and decreased synaptic plasticity (55,59).…”

Section: Figurementioning

confidence: 84%

Mutant huntingtin impairs immune cell migration in Huntington disease

Kwan¹,

et al. 2012

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In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.

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Section: Figurementioning

confidence: 84%

Mutant huntingtin impairs immune cell migration in Huntington disease

Kwan¹,

et al. 2012

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“…In addition, MAPK signaling is involved in the upregulation of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, in the hippocampus and microglia. Blockade of MAPK signaling using a specific inhibitor resulted in a reduction of the increased expression of proinflammatory cytokines induced by a stimulator [32,33]. Therefore, many studies have suggested that the inhibition of microglial activation and inflammatory responses might contribute to the prevention of white matter and hippocampal lesions [20,34].…”

Section: Discussionmentioning

confidence: 99%

Cardiotonic pill attenuates white matter and hippocampal damage via inhibiting microglial activation and downregulating ERK and p38 MAPK signaling in chronic cerebral hypoperfused rat

Lee

Bang

Han

et al. 2013

BMC Complement Altern Med

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BackgroundThe cardiotonic pill (CP) is a herbal medicine composed of Salvia miltiorrhiza (SM), Panax notoginseng (PN), and Dryobalanops aromatica Gaertner (DAG) that is widely used to treat cardiovascular diseases. The present experiment was conducted to examine the effects of CP on white matter and hippocampal damage induced by chronic cerebral hypoperfusion.MethodsChronic cerebral hypoperfusion was induced in male Wistar rats by permanent bilateral common carotid artery occlusion (BCCAo). Daily oral administration of CP (200 mg/kg) began 21 days after BCCAo and continued for 42 days. The levels of microglial activation and myelin basic protein (MBP) were measured in the white matter and hippocampus of rats with chronic BCCAo, and the expression levels of mitogen-activated protein kinases (MAPKs) and inflammatory markers such as cyclooxygenase-2, interleukin-1β, and interleukin-6 were examined.ResultsMBP expression was reduced in the white matter and hippocampal regions of rats that received BCCAo. In contrast, reduced levels of MBP were not observed in BCCAo rats given CP treatments. The administration of CP alleviated microglial activation, the alteration of ERK and p38 MAPK signaling, and inflammatory mediator expression in rats with chronic BCCAo.ConclusionThese results suggest that CP may have protective effects against chronic BCCAo-induced white matter and hippocampal damage by inhibiting inflammatory processes including microglial activation and proinflammatory mediator expression, and downreguating the hyperphosphorylation of ERK and p38 MAPK signaling.

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“…One possibility is the activation of the proapoptotic signalling molecule tumour necrosis factor alpha (TNF-a), since TNF-a production can be attenuated by blockade of p38 (Chaparro-Huerta et al 2005). TNF-a activates caspase-8, which can in turn trigger either Fig.…”

Section: Discussionmentioning

confidence: 99%

5-Hydroxyanthranilic Acid, a Tryptophan Metabolite, Generates Oxidative Stress and Neuronal Death via p38 Activation in Cultured Cerebellar Granule Neurones

Smith

Stone

2009

Neurotox Res

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The essential amino acid tryptophan is primarily metabolised through the kynurenine pathway, some components of which may be neurotoxic. We have now examined the potential toxicity of several kynurenine metabolites in relation to the generation of oxidative stress and activation of cell death signalling pathways in cultured cerebellar granule neurons. 3-Hydroxykynurenine (3HK), 3-hydroxyanthranilic acid (3HAA) and 5-hydroxyanthranilic acid (5HAA) induced cell death which increased with exposure time and compound concentration. The neurotoxic effects of 3HK, 3HAA and 5HAA were prevented by catalase, but not by superoxide dismutase. In addition, Western blot analysis demonstrated p38 activation due to 3HK or 5HAA treatment, although caspase-3 activation was not evident in either case. The results indicate that kynurenine metabolites can be neurotoxic via a caspase-3 independent mechanism, and that the minor metabolite 5HAA is as potent a toxin as the better documented compounds 3HK and 3HAA.

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Proinflammatory cytokines and apoptosis following glutamate-induced excitotoxicity mediated by p38 MAPK in the hippocampus of neonatal rats

Cited by 80 publications

References 34 publications

Mutant huntingtin impairs immune cell migration in Huntington disease

Mutant huntingtin impairs immune cell migration in Huntington disease

Cardiotonic pill attenuates white matter and hippocampal damage via inhibiting microglial activation and downregulating ERK and p38 MAPK signaling in chronic cerebral hypoperfused rat

5-Hydroxyanthranilic Acid, a Tryptophan Metabolite, Generates Oxidative Stress and Neuronal Death via p38 Activation in Cultured Cerebellar Granule Neurones

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