Perinatal protein malnutrition results in genome-wide disruptions of 5-hydroxymethylcytosine at regions that can be restored to control levels by an enriched environment
Year: 2020
Type: article
Abstract: Maternal malnutrition remains one of the major adversities affecting brain development and long-term mental health outcomes, increasing the risk to develop anxiety and depressive disorders. We have previously shown that malnutrition-induced anxiety-like behaviours can be rescued by a social and sensory stimulation (enriched environment) in male mice. Here, we expand these findings to adult female mice and profiled genome-wide ventral hippocampal 5hmC levels related to malnutrition-induced anxiety-like behaviours and their rescue by an enriched environment. This approach revealed 508 differentially hydroxymethylated genes associated with protein malnutrition and that several genes (N = 34) exhibited a restored 5hmC abundance to control levels following exposure to an enriched environment, including genes involved in neuronal functions like dendrite outgrowth, axon guidance, and maintenance of neuronal circuits (e.g. Fltr3, Itsn1, Lman1, Lsamp, Nav, and Ror1) and epigenetic mechanisms (e.g. Hdac9 and Dicer1). Sequence motif predictions indicated that 5hmC may be modulating the binding of transcription factors for several of these transcripts, suggesting a regulatory role for 5hmC in response to perinatal malnutrition and exposure to an enriched environment. Together, these findings establish a role for 5hmC in early-life malnutrition and reveal genes linked to malnutrition-induced anxious behaviours that are mitigated by an enriched environment.
Source: Epigenetics
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: Brain and Behavior Research Foundation, University of Wisconsin-Madison, National Alliance for Research on Schizophrenia and Depression, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, School of Medicine and Public Health, University of Wisconsin-Madison, Agencia Nacional de Promoción Científica y Tecnológica, National Institute of Mental Health
Awards: G2158387732, G2579832231, G439370629, G4696623542, G5586110661, G627779561, Regulación epigenética y el desarrollo de capacidades cognitivas y socio-emotivas en condiciones de estrés perinatal, Rol de la funcionalidad glial en el comportamiento de tipo ansioso y depresivo derivados de adversidades tempranas., G7075202080, Ecological footprint of bottom trawling in the Atlantic Patagonian shelf: quantification of disturbance and expected impacts on seabed habitats and communities, G8144929599, G8506066860
OpenAlex ID: W3106466980