Intergenerational trauma transmission is associated with brain metabotranscriptome remodeling and mitochondrial dysfunction

• DOI: 10.1038/s42003-021-02255-2
• Publication Date: 2021-06-24T10:02:56Z
• Authors: Sammy Alhassen; Siwei Chen; Lamees Alhassen; Alvin Phan; Mohammad Khoudari; Angele De Silva; Huda Barhoosh; Zitong Wang; Chelsea Parrocha; Emily Shapiro; Charity Henrich; Zicheng Wang; Leon Mutesa; Pierre Baldi; Geoffrey W. Abbott; Amal Alachkar
• Keywords: Hypoxia; Depression

Abstract Intergenerational trauma increases lifetime susceptibility to depression and other psychiatric disorders. Whether intergenerational transmission is a consequence of in-utero neurodevelopmental disruptions versus early-life mother–infant interaction unknown. Here, we demonstrate that exposure during pregnancy induces in mouse offspring social deficits depressive-like behavior. Normal pups raised by traumatized mothers exhibited similar behavioral those induced their biological mothers. Good caregiving normal did not reverse prenatal trauma-induced behaviors, indicating two-hit stress mechanism comprising both abnormalities poor parenting. The were associated with profound changes the brain metabotranscriptome. Striking mitochondrial hypoxia marker epigenetic modifier 2-hydroxyglutaric acid brains neonates adults exposed prenatally indicated dysfunction mechanisms. Bioinformatic analyses revealed stress- hypoxia-response metabolic pathways neonates, which produced long-lasting alterations energy metabolism processes (DNA chromatin modifications). Most strikingly, early pharmacological interventions acetyl-L-carnitine (ALCAR) supplementation protection against depression.