Biology subjects

Miguel, P. M.

Publications and source records attributed to Miguel, P. M..

2 recordsLinked to original sources

bioRxiv2026

Multilevel sex-specific neurobiological signatures of early life adversity

Stress exposure early in life is an established risk factor for adult psychiatric illness, yet these disorders - including anxiety disorders and depression - show significant sex-dependence in prevalence, symptomatology, and treatment response. The biology underlying these differences remains largely unexplored and may contribute to the clinical heterogeneity in anxiety and depression. Here, we characterize the lasting impact of developmental stress on adulthood neurobiology and behavior in mice by combining analyses of multiple levels of brain function, including whole-brain c-Fos mapping, manganese-enhanced MRI and transcriptomics with advanced behavioral phenotyping. Across levels of investigation, we find distinct and often opposite effects of developmental stress depending on sex. These results together showcase the strong influence of sex on how early life adversity affects the onset of stress-related disorders. This work emphasizes the necessity of considering sex when investigating developmental and neurobiological underpinnings of stress-related disorders and displays a vast range of lasting effects of developmental stress on the brain, which provides a valuable resource for future studies aiming to improve psychiatric treatments.

neuroscience↗

bioRxiv2025

Insulin modulates mPFC gene expression and emotional behavior in a sex-specific manner following fetal growth restriction

Exposure to prenatal adversity (e.g., stress, malnutrition) is a major risk factor for lifelong vulnerability to neuropsychiatric and metabolic disorders, and alterations in the function of peripheral hormones in the brain are suggested as a possible and unexplored mechanism. Although insulin is well known for its peripheral metabolic functions, it also influences brain development and emotional regulation, particularly within the medial prefrontal cortex (mPFC). Here, we identify insulin signaling as a key mechanistic link between prenatal stress and long-term alterations in brain function and behavior. Using a validated rat model of prenatal adversity (prenatal food restriction, FR), we found that insulin administration selectively modulates gene expression in FR animals at P0, P21 and P90, affecting pathways involved in neurodevelopment and stress regulation, such as Wnt/{beta}-catenin signaling. Targeted insulin infusion into the mPFC of adult animals reversed behavioral phenotypes induced by FR in a sex- and context-dependent manner, decreasing emotional reactivity to environmental cues. These findings offer novel insight into the neurodevelopmental role of insulin and suggest that insulin signaling may serve as a therapeutic target to mitigate the long-term brain and behavioral consequences of prenatal adversity.

genomics↗