RESUMO
BACKGROUND: Chronic stress significantly contributes to mood- and anxiety disorders. Previous data suggest a correlative connection between vitamin B12 supplementation, depression, and stress resilience. However, the underlying mechanisms are still poorly understood. METHODS: Using the chronic variable stress mouse model coupled with RNA-sequencing, we determined vitamin B12-induced transcriptional changes related to stress resilience. By viral-mediated gene transfer and in vivo epigenome editing, we reveal a functional pathway linking vitamin B12, DNA methylation, and depressive-like symptoms. RESULTS: We identified Transthyretin (Ttr) as a sex-specific key target of vitamin B12 in chronic stress. Accordingly, TTR expression was increased postmortem in the prefrontal cortex of male, but not female, depressed patients. Virally altered Ttr in the prefrontal cortex functionally contributed to stress- and depression-related behaviors, changes in dendritic spine morphology, and gene expression. In stressed mice, vitamin B12 reduced DNAme in the Ttr promoter region. Importantly, using in vivo epigenome editing to alter DNAme in the brains of living mice for the first time, we establish a direct causal link between DNAme on Ttr and stress-associated behaviors. DISCUSSION: Using state-of-the-art techniques, this study uncovers a mechanistic link between vitamin B12 supplementation, Ttr, and markers of chronic stress and depression, encouraging further studies into dietary interventions for mood disorders.
RESUMO
Un equipo multidisciplinario inicia en la Unidad de Neonatología de un hospital público el programa de Apoyo al Desarrollo Biopsicosocial. En familias de RN que permanecen en UCI, hospitalizados más de 20 días, embarazos no controlados y en aquellas en quienes se observan dificultades emocionales para el vínculo, se investiga factores de riesgo y protección en salud mental. Con un enfoque de vulnerabilidad-resiliencia se estudian factores biológicos, psicológicos y sociocomunitarios que intervienen en el desarrollo de un vínculo de apego seguro, detectándose una alta frecuencia de alteraciones de la salud mental susceptibles de tratamiento, en un momento del ciclo vital familiar que ofrece una ventana de oportunidad para el cambio. Es un trabajo exploratorio de investigación acción, que ha ofrecido contención emocional y apoyo a las familias estudiadas.
A multidisciplinary team works on a newborn unit at a public hospital beginning a Biopsycosocial development help program. In families of UCI babies, over 20 days hospitalization babies, uncontrolled pregnancies and observed bonding difficulties on goes a mental health research under vulnerability-resilience paradigm. Biological, psychological and sociocomunitary factors involved in attachment are studied, founding high frecuency of treatable mental health problems, in a very sensible moment of family life cicle, proper to changes. It is an exploratory action research, that offered emotional holding and support on studied families.