RGD Reference Report - Epigenetic modulation of neuronal apoptosis and cognitive functions in sepsis-associated encephalopathy. - Rat Genome Database

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Epigenetic modulation of neuronal apoptosis and cognitive functions in sepsis-associated encephalopathy.

Authors: Fang, J  Lian, Y  Xie, K  Cai, S  Wen, P 
Citation: Fang J, etal., Neurol Sci. 2014 Feb;35(2):283-8. doi: 10.1007/s10072-013-1508-4. Epub 2013 Aug 8.
RGD ID: 9681446
Pubmed: PMID:23925573   (View Abstract at PubMed)
DOI: DOI:10.1007/s10072-013-1508-4   (Journal Full-text)

Sepsis-associated encephalopathy (SAE), which associates with neuronal apoptosis and cognitive disorders, is a common complication of systemic sepsis. However, the mechanism involving its modulation remains to be elucidated. Recent studies showed that histone deacetylases (HDACs) were implicated in neurodegeneration and cognitive functions. The current study was designed to investigate whether septic brain is epigenetically modulated by HDACs, using cecal ligation and peroration (CLP) rats and primary hippocampal neuronal cultures. We found that hippocampal acetylated histone 3 (AcH3), acetylated histone 4 (AcH4), cytoplasmic HDAC4 and Bcl-XL were inhibited in septic brain. Hippocampal Bax and nuclear HDAC4 expressions were enhanced in CLP rats. Administration of HDACs inhibitor, trichostatin A (TSA) or suberoylanilide hydroxamic acid (SAHA) rescued the changes of Bcl-XL and Bax in vivo, and decreased apoptotic cells in vitro. In addition, HDAC4 shRNA transfection significantly enhanced AcH3, AcH4 and Bcl-XL, but suppressed Bax. Neuronal apoptosis was also reduced by transfection of HDAC4 shRNA. Furthermore, CLP rats exhibited significant spatial learning and memory deficits, which could be ameliorated by application of TSA or SAHA without influence on locomotive activity. These results reveal that epigenetic modulation is involved in septic brain, and the inhibition of HDACs may serve as a potential therapeutic approach for SAE treatment.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Sepsis  ISOHdac4 (Rattus norvegicus)9681446; 9681446 RGD 
Sepsis  IEP 9681446 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of neuron apoptotic process  IMP 9681446 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hdac4  (histone deacetylase 4)

Genes (Mus musculus)
Hdac4  (histone deacetylase 4)

Genes (Homo sapiens)
HDAC4  (histone deacetylase 4)


Additional Information