Protective Effects of p38 MAPK Inhibitor SB202190 against Hippocampal Apoptosis and Spatial Learning and Memory Deficits in a Rat Model of Vascular Dementia

Shen, Yang; Guang-an, Zhou; Liu, Hong; Zhang, Bo; Li, Juan; Cui, Ruiting; Du, Yifeng

doi:10.1155/2013/215798

Cited by 50 publications

(27 citation statements)

References 33 publications

(41 reference statements)

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“…8). A blockade of the p38 MAPK signaling pathway by SB202190 following permanent BCCAO reduced apoptosis of hippocampal neurons and rescued spatial learning and memory deficits [21]. In our study, we found that application of the p38 MAPK inhibitor SB203580 also rescued the cognitive impairment of VD rats.…”

Section: Discussionsupporting

confidence: 64%

Contribution of p38 MAPK to the Ameliorating Effect of Enriched Environment on the Cognitive Deficits Induced by Chronic Cerebral Hypoperfusion

Yuwang

Wang

et al. 2016

Cell Physiol Biochem

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Background/Aims: An enriched environment (EE) ameliorates learning and memory impairments induced by chronic cerebral hypoperfusion, and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway exerts both beneficial and deleterious effects on the nervous system during the progression of ischemia. Methods: The present study investigated whether p38 MAPK participates in the process by which EE exposure ameliorates the cognitive deficits induced by chronic cerebral hypoperfusion. Results: EE exposure significantly enhanced the cognitive performance of vascular dementia (VD) model rats, and p38 MAPK protein decreased in parallel with cognitive improvements. Inhibition of p38 MAPK function by its selective inhibitor SB203580 improved the cognition index of VD rats and upregulated p38 MAPK expression with p38 MAPK antisense oligodeoxynucleotides. This impaired cognition in VD rats could not be rescued by EE exposure. Conclusion: p38 MAPK participates in the process by which EE exposure ameliorates cognitive deficits induced by chronic cerebral hypoperfusion.

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Section: Discussionsupporting

confidence: 64%

Contribution of p38 MAPK to the Ameliorating Effect of Enriched Environment on the Cognitive Deficits Induced by Chronic Cerebral Hypoperfusion

Yuwang

Wang

et al. 2016

Cell Physiol Biochem

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“…Activation of p38 MAP kinase has also been identified in neurons exposed to 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), neurotoxins that triggers ROS production and are implicated in the mechanism of cell death (Du et al, 2001; Choi et al, 2004). In vivo studies in animal models of vascular dementia also showed activation of p38 MAP kinase in the hippocampus resulting in neurological dysfunction (Yang et al, 2013). Similarly a growing number of studies have established a role of ERK MAP kinase in neuronal injury following depletion of intracellular GSH level or induction of oxidative stress by H 2 O 2 (Du et al, 2002; de Bernardo et al, 2004; Luo et al, 2007; Numakawa et al, 2007; Tuerxun et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Aging is associated with dimerization and inactivation of the brain-enriched tyrosine phosphatase STEP

Rajagopal

Deb

Poddar

et al. 2016

Neurobiology of Aging

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The striatal-enriched tyrosine phosphatase (STEP) is involved in the etiology of several age-associated neurological disorders linked to oxidative stress and is also known to play a role in neuroprotection by modulating glutamatergic transmission. However, the possible effect of aging on STEP level and activity in the brain is still unclear. In this study, using young (1 month), adult (4 month) and aged (18 month) rats we show that aging is associated with increase in dimerization and loss of activity of STEP. Increased dimerization of STEP is primarily observed in the cortex and hippocampus and is associated with depletion of both reduced and total glutathione levels, suggesting an increase in oxidative stress. Consistent with this interpretation studies in cell culture models of glutathione depletion and oxidative stress also demonstrates formation of dimers and higher order oligomers of STEP that involves intermolecular disulfide bond formation between multiple cysteine residues. Conversely, administration of N-acetyl cysteine, a major antioxidant that enhances glutathione biosynthesis, attenuates STEP dimerization both in the cortex and hippocampus. The findings indicate that loss of this intrinsic protective response pathway with age-dependent increase in oxidative stress may be a contributing factor for the susceptibility of the brain to age-associated neurological disorders.

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“…The kinase proteins include cAMP-dependent protein kinases (PKA), phosphatidylinositol triphosphate-dependent kinase (PI-3K), protein kinase B (AKT or PKB), protein kinase C isoforms (PKC), calcium-calmodulin-dependent protein kinases (CAMK), glycogen synthase kinase-3β (GSK3β), stress activated mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal protein kinase (JNK) and p38 kinase (p38K), and receptor-mediated tyrosine kinases. In addition, the activities of these kinases are generally altered in pathological conditions, including neurodegenerative diseases (Ferraris et al, 2013; Ron and Messing, 2013; Yang et al, 2013; Yin et al, 2013). These kinases can work independently or together synergistically or antagonize each other’s activities.…”

Section: Consequences Of Increased Nitroxidative Stressmentioning

confidence: 99%

Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress

et al. 2016

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Mitochondria are important for providing cellular energy ATP through the oxidative phosphorylation pathway. They are also critical in regulating many cellular functions including the fatty acid oxidation, the metabolism of glutamate and urea, the anti-oxidant defense, and the apoptosis pathway. Mitochondria are an important source of reactive oxygen species leaked from the electron transport chain while they are susceptible to oxidative damage, leading to mitochondrial dysfunction and tissue injury. In fact, impaired mitochondrial function is commonly observed in many types of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, alcoholic dementia, brain ischemia-reperfusion related injury, and others, although many of these neurological disorders have unique etiological factors. Mitochondrial dysfunction under many pathological conditions is likely to be promoted by increased nitroxidative stress, which can stimulate post-translational modifications (PTMs) of mitochondrial proteins and/or oxidative damage to mitochondrial DNA and lipids. Furthermore, recent studies have demonstrated that various antioxidants, including naturally occurring flavonoids and polyphenols as well as synthetic compounds, can block the formation of reactive oxygen and/or nitrogen species, and thus ultimately prevent the PTMs of many proteins with improved disease conditions. Therefore, the present review is aimed to describe the recent research developments in the molecular mechanisms for mitochondrial dysfunction and tissue injury in neurodegenerative diseases and discuss translational research opportunities.

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Protective Effects of p38 MAPK Inhibitor SB202190 against Hippocampal Apoptosis and Spatial Learning and Memory Deficits in a Rat Model of Vascular Dementia

Cited by 50 publications

References 33 publications

Contribution of p38 MAPK to the Ameliorating Effect of Enriched Environment on the Cognitive Deficits Induced by Chronic Cerebral Hypoperfusion

Contribution of p38 MAPK to the Ameliorating Effect of Enriched Environment on the Cognitive Deficits Induced by Chronic Cerebral Hypoperfusion

Aging is associated with dimerization and inactivation of the brain-enriched tyrosine phosphatase STEP

Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress

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