Dataset Information

Chromatin organization in the female mouse brain fluctuates across the oestrous cycle.

ABSTRACT: Male and female brains differ significantly in both health and disease, and yet the female brain has been understudied. Sex-hormone fluctuations make the female brain particularly dynamic and are likely to confer female-specific risks for neuropsychiatric disorders. The molecular mechanisms underlying the dynamic nature of the female brain structure and function are unknown. Here we show that neuronal chromatin organization in the female ventral hippocampus of mouse fluctuates with the oestrous cycle. We find chromatin organizational changes associated with the transcriptional activity of genes important for neuronal function and behaviour. We link these chromatin dynamics to variation in anxiety-related behaviour and brain structure. Our findings implicate an immediate-early gene product, Egr1, as part of the mechanism mediating oestrous cycle-dependent chromatin and transcriptional changes. This study reveals extreme, sex-specific dynamism of the neuronal epigenome, and establishes a foundation for the development of sex-specific treatments for disorders such as anxiety and depression.

SUBMITTER: Jaric I

PROVIDER: S-EPMC6598989 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Chromatin organization in the female mouse brain fluctuates across the oestrous cycle.

Jaric Ivana I Rocks Devin D Greally John M JM Suzuki Masako M Kundakovic Marija M

Nature communications 20190628 1

Male and female brains differ significantly in both health and disease, and yet the female brain has been understudied. Sex-hormone fluctuations make the female brain particularly dynamic and are likely to confer female-specific risks for neuropsychiatric disorders. The molecular mechanisms underlying the dynamic nature of the female brain structure and function are unknown. Here we show that neuronal chromatin organization in the female ventral hippocampus of mouse fluctuates with the oestrous ...[more]

PMID: 31253786

Similar Datasets

Project description:Brain structure and function are sexually dimorphic. As neuroscience research has largely focused on the male brain and behavior, the female brain and, in particular, its inherent dynamics have been left underexplored. During the mammalian reproductive period, the female brain is exposed to fluctuating hormone levels over the cycles known as menstrual (in humans) or estrous (in rodents). Variation in estradiol levels has been shown to affect synaptic plasticity in the female brain, including changes in dendritic spine density systematically across the estrous cycle. Female emotionality and cognitive function vary with physiologically fluctuating sex hormone levels. However, the molecular mechanisms underlying the dynamic nature of the female brain structure and function are currently unknown. Here we show that neuronal chromatin organization in the female ventral hippocampus of mouse is dynamic and fluctuates across the estrous cycle. We find changes in chromatin organization associated with the transcriptional activity of nearby genes important for neuronal function, neurotransmission, synapse formation, and behavior. We also link these chromatin dynamics to variation in anxiety-like behavior and to fluctuations in dendritic spine and synaptic density in the ventral hippocampus. In terms of chromatin structure, within-female and between-sex variation are of similar magnitudes, emphasizing the importance of accounting for fluctuating sex-hormone levels in females in the studies of the brain epigenome and behavior. These results provide critical insights into the mechanisms underlying sex-hormone and sex-dependent variation in adult brain structure and function. The study also has implications for better understanding of sex-biased disorders such as depression and anxiety which are strongly associated with sex-hormone status in females and are twice as prevalent in women than in men. This study establishes a foundation for the development of sex-specific approaches to treat sex-biased neuropsychiatric disorders including depression and anxiety disorders.

Dataset Information

Chromatin organization in the female mouse brain fluctuates across the oestrous cycle.

Publications

Chromatin organization in the female mouse brain fluctuates across the oestrous cycle.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets