| First Author | Corbett BF | Year | 2017 |
| Journal | Cell Rep | Volume | 20 |
| Issue | 2 | Pages | 344-355 |
| PubMed ID | 28700937 | Mgi Jnum | J:255467 |
| Mgi Id | MGI:6107726 | Doi | 10.1016/j.celrep.2017.06.040 |
| Citation | Corbett BF, et al. (2017) DeltaFosB Regulates Gene Expression and Cognitive Dysfunction in a Mouse Model of Alzheimer's Disease. Cell Rep 20(2):344-355 |
| abstractText | Alzheimer''s disease (AD) is characterized by cognitive decline and 5- to 10-fold increased seizure incidence. How seizures contribute to cognitive decline in AD or other disorders is unclear. We show that spontaneous seizures increase expression of DeltaFosB, a highly stable Fos-family transcription factor, in the hippocampus of an AD mouse model. DeltaFosB suppressed expression of the immediate early gene c-Fos, which is critical for plasticity and cognition, by binding its promoter and triggering histone deacetylation. Acute histone deacetylase (HDAC) inhibition or inhibition of DeltaFosB activity restored c-Fos induction and improved cognition in AD mice. Administration of seizure-inducing agents to nontransgenic mice also resulted in DeltaFosB-mediated suppression of c-Fos, suggesting that this mechanism is not confined to AD mice. These results explain observations that c-Fos expression increases after acute neuronal activity but decreases with chronic activity. Moreover, these results indicate a general mechanism by which seizures contribute to persistent cognitive deficits, even during seizure-free periods. |
