RGD Reference Report - Reduction of hippocampal apoptosis by intracerebroventricular administration of extracellular signal-regulated protein kinase and/or p38 inhibitors in amyloid beta rat model of Alzheimer's disease: involvement of nuclear-related factor-2 and nuclear factor-kappaB. - Rat Genome Database

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Reduction of hippocampal apoptosis by intracerebroventricular administration of extracellular signal-regulated protein kinase and/or p38 inhibitors in amyloid beta rat model of Alzheimer's disease: involvement of nuclear-related factor-2 and nuclear factor-kappaB.

Authors: Ashabi, G  Alamdary, SZ  Ramin, M  Khodagholi, F 
Citation: Ashabi G, etal., Basic Clin Pharmacol Toxicol. 2013 Mar;112(3):145-55. doi: 10.1111/bcpt.12000. Epub 2012 Oct 5.
RGD ID: 10412685
Pubmed: PMID:22913737   (View Abstract at PubMed)
DOI: DOI:10.1111/bcpt.12000   (Journal Full-text)

In the present study, we examined the effects of intracerebroventricular administration of extracellular signal-regulated protein kinase- (ERK) and p38-specific inhibitors, U0126 and PD169316, respectively, on apoptosis induced by amyloid beta (Abeta) in rats. To investigate the effects of these compounds, we evaluated intracellular signalling pathways of apoptosis, as well as inflammatory and antioxidant pathways, 7 and 20 days after Abeta injection. We found that caspase-3 and Bax/Bcl-2 ratio, two hallmarks of apoptosis, were significantly decreased in the rats pre-treated with U0126 and PD169316, 7 days after Abeta injection. This observation was in agreement with the results of immunostaining analysis of the hippocampus that showed decreased levels of terminal transferase dUTP nick end labelling positive cells in the hippocampus of U0126 and PD169316 pre-treated rats, compared with the Abeta-injected group. We also chased the changes in the levels of calpain-2 and caspase-12, two ER factors, in the Abeta-injected and treatment groups. Decreased levels of calpain-2 and caspase-12 in U0126 and PD169316 pre-treated rats confirmed the protective effects of these inhibitors. Furthermore, we studied the effect of two stress-sensing transcription factors, nuclear-related factor-2 (Nrf2) and nuclear factor-small ka, CyrillicB (NF-small ka, CyrillicB), in Abeta-injected as wells as U0126 and PD169316 pre-treated rats. U0126 and PD169316 activated Nrf2 and suppressed NF-small ka, CyrillicB pathways, 7 days after Abeta injection. These antioxidant and inflammatory pathways restored to the vehicle level within 20 days. Taken together, our findings reinforce and extend the notion of the potential neuroprotective role of ERK and/or p38 inhibitors against the neuronal toxicity induced by Abeta.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease treatmentISONfe2l2 (Rattus norvegicus)10412685; 10412685 RGD 
Alzheimer's disease treatmentIEP 10412685 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nfe2l2  (NFE2 like bZIP transcription factor 2)

Genes (Mus musculus)
Nfe2l2  (nuclear factor, erythroid derived 2, like 2)

Genes (Homo sapiens)
NFE2L2  (NFE2 like bZIP transcription factor 2)


Additional Information