RGD Reference Report - Phosphorylation of histone H2A.X as an early marker of neuronal endangerment following seizures in the adult rat brain. - Rat Genome Database

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Phosphorylation of histone H2A.X as an early marker of neuronal endangerment following seizures in the adult rat brain.

Authors: Crowe, SL  Tsukerman, S  Gale, K  Jorgensen, TJ  Kondratyev, AD 
Citation: Crowe SL, etal., J Neurosci. 2011 May 25;31(21):7648-56. doi: 10.1523/JNEUROSCI.0092-11.2011.
RGD ID: 8693708
Pubmed: PMID:21613478   (View Abstract at PubMed)
PMCID: PMC3118469   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.0092-11.2011   (Journal Full-text)

The phosphorylated form of histone H2A.X (gamma-H2AX) is a well documented early, sensitive, and selective marker of DNA double-strand breaks (DSBs). Previously, we found that excessive glutamatergic activity increased gamma-H2AX in neurons in vitro. Here, we evaluated gamma-H2AX formation in the adult rat brain following neuronal excitation evoked by seizure activity in vivo. We found that brief, repeated electroconvulsive shock (ECS)-induced seizures (three individual seizures within 60 min) did not trigger an increase gamma-H2AX immunostaining. In contrast, a cluster of 5-7 individual seizures evoked by kainic acid (KA) rapidly (within 30 min) induced gamma-H2AX in multiple neuronal populations in hippocampus and entorhinal cortex. This duration of seizure activity is well below threshold for induction of neuronal cell death, indicating that the gamma-H2AX increase occurs in response to sublethal insults. Moreover, an increase in gamma-H2AX was seen in dentate granule cells, which are resistant to cell death caused by KA-evoked seizures. With as little as a 5 min duration of status epilepticus (SE), gamma-H2AX increased in CA1, CA3, and entorhinal cortex to a greater extent than that observed after the clusters of individual seizures, with still greater increases after 120 min of SE. Our findings provide the first direct demonstration that DNA DSB damage occurs in vivo in the brain following seizures. Furthermore, we found that the gamma-H2AX increase caused by 120 min of SE was prevented by neuroprotective preconditioning with ECS-evoked seizures. This demonstrates that DNA DSB damage is an especially sensitive indicator of neuronal endangerment and that it is responsive to neuroprotective intervention.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
status epilepticus  ISOH2ax (Rattus norvegicus)8693708; 8693708protein:increased phosphorylation:brainRGD 
status epilepticus  IDA 8693708protein:increased phosphorylation:brainRGD 

Objects Annotated

Genes (Rattus norvegicus)
H2ax  (H2A.X variant histone)

Genes (Mus musculus)
H2ax  (H2A.X variant histone)

Genes (Homo sapiens)
H2AX  (H2A.X variant histone)


Additional Information