PhD Scientific Days 2025

Poster Session I. - Q: Neurosciences

Sex-specific Long-term Behavioural and Neuroimmunological Consequences of Perinatal Brain Injury

Name of the presenter

Kelemen Hanga

Institute/workplace of the presenter

HUN-REN Institute of Experimental Medicine, Semmelweis University

Authors

Hanga Kelemen^1,2, András Buzás-Kaizler^1,2, Gyula Balla^1,2, Kornél Demeter¹, Zsolt Borhegyi¹, Éva Mikics¹

1: HUN-REN Institute of Experimental Medicine
2: Semmelweis University

Text of the abstract

Perinatal systemic inflammation and asphyxia (ASX) are major risk factors of neuropsychiatric disorders, often showing sex-specific outcomes - cognitive deficits more common in males and altered emotional processing in females. When these two conditions co-occur, they exacerbate clinical outcomes, suggesting shared pathophysiology. However, how prior inflammation sensitizes the brain to ASX remains unclear due to a lack of translational models. In this study, we examined the long-term behavioural and neuroimmune consequences of mild to moderate ASX in inflammation-sensitized C75BL/6 mice of both sexes.
Pups received s.c. IL-1β between postnatal days 2-6, followed by a non-invasive ASX insult on day 7. A comprehensive behavioural battery was conducted in young adulthood, followed by whole-brain microglial density mapping to determine neuroimmune alterations.
Behavioural testing revealed a significant phenotype shift of ASX+IL-1 males compared to controls, affecting domains of specific higher-order functions, including impulse control, emotional, and cognitive processing. In contrast, ASX+IL-1 females exhibited more subtle behavioural alterations, primarily characterized by disruptions in emotional regulation (heightened anxiety and passive stress coping). Whole-brain microglia density analysis revealed regional increase in ASX+IL-1 males, particularly in areas associated with the noted behavioural changes (e.g., mediodorsal thalamus, nucleus reuniens, basolateral amygdala). Females also exhibited neuroimmune alterations, notably in emotional regulation hubs like the infralimbic cortex and nucleus accumbens, despite milder behavioural symptoms.
These results demonstrate that early-life systemic inflammation significantly increases ASX vulnerability, leading to persistent, sex-specific behavioural deficits analogous to clinical outcomes. Accordingly, brain regions involved in higher-order processing show particular vulnerability to early-life injury and present lasting neuroimmune alterations. Our findings underline the translational utility of our preclinical model in elucidating the underlying pathophysiological mechanisms of perinatal brain injuries that contribute to neurodevelopmental disorders.
National Laboratory of Translational Neuroscience (Grant #RRF-2.3.1-21-2022-00011) and National Research, Development, and Innovation Office (Grant #K135292).