PhD Scientific Days 2024

Poster Session I - Neurosciences 2.

Perinatal brain injury leads to sexually dimorphic long-term behavioural deficits in mice

Előadó neve

Kelemen, Hanga

Neptun code

LDCH7F

Előadó munkahelye

Institute of Experimental Medicine

Előadó telefonszáma

+36705948234

Előadó e-mail címe

hanga_kelemen@yahoo.com

Az előadás címe

Perinatal brain injury leads to sexually dimorphic long-term behavioural deficits in mice

Szerző(k) neve és munkahelye

Hanga Kelemen¹, Gyula Balla¹, András Buzás-Kaizler¹, Kornél Demeter¹, Zsolt Borhegyi¹, Éva Mikics¹

1: Institute of Experimental Medicine

Bemutatás módja

Poszter

Szekció

Poster Session I - Neurosciences 2.

Language of the presentation

English

Preferred session

Neurosciences

Összefoglaló szövege

Hypoxic-ischaemic encephalopathy caused by perinatal asphyxia (PA) is a leading cause of neonatal mortality and a significant contributor to long-term neuropsychiatric deficits in cases of mild-moderate severity. In utero systemic inflammation is known to enhance PA-vulnerability, contributing to a cumulative negative effect on neuropsychiatric outcome, which often shows sex-dependent manifestations. However, the lack of translational preclinical models is hindering the exploration of causative mechanisms behind inflammatory presensitization-induced increase in PA-sensitivity. Proinflammatory cytokine IL-1β plays a key role in both pathophysiological cascades, possibly contributing to their interactive effects. Here we aimed to determine the long-term behavioural consequences and histological alterations of mild PA in inflammation-sensitized mice of both sexes. For this, C75BL/6 mouse pups received s.c. IL-1β between P2-P6 and/ or a non-invasive PA insult on P7, resulting in treatment groups of IL-1 + PA, IL-1, PA or control. Behavioural consequences were examined in automated (Automated Trainig System, IntelliCage) and classical paradigms through young adulthood. Afterwards, brain tissue was collected and unbiased histological analysis of Iba1(+) microglia was performed. Both sexes exhibited alterations in emotionality (higher anxiety and impulsivity) due to IL-1 and/or PA treatment. Cognitive domains were most significantly affected in males of IL-1 + PA group (diminished learning abilities and cognitive inflexibility). Females were more substantially affected in stress-coping. Histological analysis revealed long-lasting increase in microglia numbers in the mammillary body, basolateral amygdala and multiple thalamic nuclei of males, all related to cognitive and emotional functioning. Our results suggest that early-life inflammation and PA can solely lead to long-term behavioural deficits in a sex-specific manner, with a considerable aggravating effect of an IL-1 mediated inflammatory cascade on PA-vulnerability. Further analysis of long-lasting alterations in microglia functioning is needed to elucidate the underlying mechanisms behind the sexually dimorphic behavioural deficits in adulthood.
Funding: National Laboratory of Translational Neuroscience (Grant# RRF-2.3.1-21-2022-00011) and National Research, Development and Innovation Office (Grant# K135292).

University

Semmelweis University

Supervisor

Éva Mikics

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6909

Start

15:30

End

15:33