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

Vascular dementia (VaD) is a common age-related neurodegenerative disease resulting from chronic hypoxia. In the present study, we examined the protective effects of p38 MAPK inhibitor SB202190 against hippocampal apoptosis and spatial learning and memory deficits in a chronic hypoperfusion rat mode...

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Publicado en:BioMed Research International Vol. 2013; pp. 215798 - 215799
Autores principales: Yang, Shen, Zhou, Guangan, Liu, Hong, Zhang, Bo, Li, Juan, Cui, Ruiting, Du, Yifeng
Formato: research Journal Article
Publicado: Wiley-Blackwell 2013
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2013
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        atl: Protective Effects of p38 MAPK Inhibitor SB202190 against Hippocampal Apoptosis and Spatial Learning and Memory Deficits in a Rat Model of Vascular Dementia.
      aug:
        au:
          Yang, Shen
          Zhou, Guangan
          Liu, Hong
          Zhang, Bo
          Li, Juan
          Cui, Ruiting
          Du, Yifeng
        affil: Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan 250012, China ; Department of Neurology, Taian Central Hospital, Taian 271000, China.
      sug:
        subj:
          Imidazoles Administration and Dosage
          Learning Disorders Drug Therapy
          Memory Disorders Drug Therapy
          Pyridines Administration and Dosage
          Transferases Metabolism
          Animal Studies
          Apoptosis Drug Effects
          Dementia, Vascular Drug Therapy
          Dementia, Vascular Physiopathology
          Genes Drug Effects
          Hippocampus Drug Effects
          Human
          Learning Disorders Physiopathology
          Memory Disorders Physiopathology
          Models, Biological
          Neurons Drug Effects
          Neurons Metabolism
          Proteins
          Rats
          Transferases
          Transferases Antagonists and Inhibitors
      ab: Vascular dementia (VaD) is a common age-related neurodegenerative disease resulting from chronic hypoxia. In the present study, we examined the protective effects of p38 MAPK inhibitor SB202190 against hippocampal apoptosis and spatial learning and memory deficits in a chronic hypoperfusion rat model of VaD established by permanent bilateral carotid occlusion (2-VO). Sixty rats were randomly divided into sham-operated, VaD model, and VaD plus SB202190 groups (n = 20/group). After sham/2-VO surgery, rats were administered 0.1% DMSO (sham-operated and VaD groups) or SB202190 by intracerebroventricular injection. One week after inhibitor/vehicle treatment, hippocampal p38 MAPK phosphorylation was higher in the model group than in the SB202190 group (P < 0.01). Compared to the model group, the SB202190 group exhibited significantly shorter escape latencies in the Morris water maze hidden platform trials (P < 0.01) and longer times in the original platform quadrant during probe trials (P < 0.01). The SB202190 group also showed significantly reduced neuronal apoptosis in the hippocampus compared to VaD model rats (P < 0.01) as well as higher (antiapoptotic) Bcl-2 expression and lower (proapoptotic) caspase-3 expression (P < 0.01 for both). In conclusion, blockade of the p38 MAPK signaling pathway by SB202190 following permanent 2-OV reduced apoptosis of hippocampal neurons and rescued spatial learning and memory deficits.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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