Special Lecture | Lombroso Lecture: Seizure-induced Epigenetic Regulation of Cognition in Alzheimer's Disease

OVERVIEW:

Recurrent seizures accompany a number of neurological disorders and are associated with cognitive deficits. However, the mechanisms by which seizures impair cognition have yet to be fully defined, particularly for conditions in which seizures are relatively infrequent, such as Alzheimer's disease (AD). This lecture will review recent studies demonstrating that seizures induce activity-dependent expression of ∆FosB, a transcription factor with an unusually long half-life, which epigenetically suppresses the expression of target genes that are critical for plasticity and memory. Chromatin-immunoprecipitation (ChIP) sequencing studies indicate that ∆FosB regulates several domains of neuronal function including excitability and neurotransmission, chromatin remodeling, neurogenesis, and cellular stress. These studies shed light on mechanisms by which even infrequent seizures can lead to persistent changes in neuronal function and cognition in Alzheimer's disease, with implications for other neurological disorders.