Language
English
Publication Date
7-1-2026
Journal
Neurobiology of Stress
DOI
10.1016/j.ynstr.2026.100825
PMID
42291690
PMCID
PMC13254890
PubMedCentral® Posted Date
5-28-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Early life adversity (ELA) can increase incidences of psychopathology later in life, partly through aberrant expression of the brain-derived neurotrophic factor (Bdnf) gene. One mechanism whereby ELA can alter Bdnf expression is through DNA methylation, typically reducing expression. Previously, our lab has utilized a predator odor model of ELA, whereby dams with their pups are exposed to either 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a synthetic derivative of fox feces, or butyric acid (BTA) as a noxious control for the first three postnatal weeks. Developmental exposure to TMT reduced adolescent freezing to TMT, suggesting the presence of the caregiver may be buffering later fear responses. However, the contribution of the caregiver versus mere developmental exposure remains unclear. In the present study, pups with or without their dams present were exposed to either TMT or BTA for the first three weeks of life. We subsequently assessed TMT-induced freezing, general anxiety-like behaviors in the open-field test, and collected brain tissue from the medial prefrontal cortex , amygdala, and periaqueductal gray at key developmental timepoints to assess Bdnf expression and DNA methylation. Results indicated that maternal separation increased freezing to TMT in males, lowered 40 kHz vocalizations, increased anxiety-like behavior, and produced epigenetic changes of Bdnf in a region and age-specific manner. Together, our data illustrate the powerful effects of brief disruptions in the caregiving environment on brain methylation and behavior. Such data help deepen our understanding of neurobiological mechanisms impacted by ELA and a potential underlying root cause of psychopathology.
Keywords
Predator odor, Maternal separation, Epigenetic, DNA methylation, mPFC, Amygdala, PAG
Published Open-Access
yes
Recommended Citation
Bigham, Olivia; Ayers, Luke W; Rosen, Jeffrey B; et al., "Maternal Separation Increases Anxiety-Like Phenotypes, Fear Responses, and Alters Bdnf Methylation in a Predator Odor Exposure Model of Early Life Adversity" (2026). Faculty, Staff and Students Publications. 8258.
https://digitalcommons.library.tmc.edu/baylor_docs/8258