Tanay Shah
Research Mentor: Gabriel Corfas
Mentor Department: Kesge Hearing Research Institute, Medicine
Author(s): Tanay Shah, Dr. Gabriel Corfas, Dr. Beatriz C Borges Del Grande
Session: Session 6 (3:00 PM – 3:50 PM)
Presentation Type: Poster 17
Abstract
Based on previous data from the Corfas Lab, social isolation of mice between 21 and 35 post natal days reduces the expression of Neuregulin 1 (NRG1) in the prefrontal cortex (PFC), resulting in lower rates of PFC myelination and impaired PFC function. This trophic factor, NRG1, and its isoforms, Type I, II, and III, has been shown to affect myelination, synaptic plasticity, neural development, and various other neural processes. Other studies have shown memory, behavior, and physiology in mice are affected by housing conditions. When mice are reintroduced to a social environment, these changes aren’t reversed, meaning that epigenetic mechanisms may play a role in long lasting effects of social isolation. We investigated the roles of histone deacetylation, a mechanism for epigenetics in the impact of social isolation on PFC NRG1. We evaluated the effect that social isolation has on the expression and enzymatic activity of histone deacetylases (HDACs). In addition, we evaluated acetylation marks in PFC neurons and if reducing the activity of HDAC during social isolation reverses the impact that it has on NRG1 expression. Immediately after weaning (P21), male mice were divided into two groups: regular housing (RH), consisting of five mice per cage, and socially isolated (SI), consisting of one mouse per cage. After two weeks (P35), mice were euthanized, and the PFC was dissected to study mRNA and protein expression. Another set of CamK2a-creERT:: HDAC3 fl/fl mice and its controls were treated with 100mg/kp ip tamoxifen from P18-P21, before the isolation period. Socially isolated mice had higher HDAC activity and reduced expression of AcH4K8 in the PFC. When HDAC3 was removed from CamK2a+ expressing neurons, the reduction in NRG1 was attenuated, suggesting a role of HDAC3 on regulation of PFC NRG1 expression during SI.
