Biology subjects

Naler, L. B.

Publications and source records attributed to Naler, L. B..

2 recordsLinked to original sources

bioRxiv2021

Prolonged epigenetic and synaptic plasticity alterations following single exposure to a psychedelic in mice

Clinical evidence suggests a potential therapeutic effect of classic psychedelics for the treatment of depression. The most outstanding and distinct characteristic is the rapid and sustained antidepressant action with one single exposure to the drug. However, the biological substrates and key mediators of psychedelics enduring action remain unknown. Here, we show that a single administration of the psychedelic DOI produced fast-acting effects on frontal cortex dendritic spine structure and acceleration of fear extinction via the 5-HT2A receptor. Additionally, a single dose of DOI led to changes in chromatin organization particularly at enhancer regions of genes involved in synaptic assembly that stretched for days after the psychedelic exposure. DOI-induced alterations in neuronal epigenome overlapped with genetic loci associated with schizophrenia, depression and attention deficit hyperactivity disorder. Together, these data support the notion that epigenetic-driven changes in synaptic plasticity operate as the mechanistic substrate of psychedelics long-lasting antidepressant action but also warn on the limitations in individuals with underlying risk for psychosis.

neuroscience↗

bioRxiv2020

Cell-type-specific epigenomic variations associated with BRCA1 mutation in pre-cancer human breast tissues

BRCA1 germline mutation carriers are predisposed to breast cancers. Epigenomic regulations have been known to strongly interact with genetic variations and potentially mediate biochemical cascades involved in tumorigenesis. Due to the cell-type specificity of epigenomic features, profiling of individual cell types is critical for understanding the molecular events in various cellular compartments within complex breast tissue. Here we report cell-type-specific profiling of genome-wide histone modifications including H3K27ac and H3K4me3 in basal, luminal progenitor, mature luminal, and stromal cells extracted from pre-cancer BRCA1 mutation carriers and non-carriers, conducted using a low-input technology that we developed. We discover that basal and stromal cells present the most extensive epigenomic differences between mutation carriers (BRCA1mut/+) and non-carriers (BRCA1+/+) while luminal progenitor and mature luminal cells are relatively unchanged with the mutation. Furthermore, the epigenomic changes in basal cells due to BRCA1 mutation appear to facilitate their transformation into luminal progenitor cells. Our findings shed light on the pre-cancer epigenomic dynamics due to BRCA1 mutation and how they may contribute to eventual development of predominantly basal-like breast cancer.

genomics↗