PhD Scientific Days 2023

Budapest, 22-23 June 2023

Neurosciences - Posters H

The Role of Inflammation-induced Sensitization in Long-term Behavioural Deficits in a Mouse Model of Perinatal Asphyxia

Hanga Kelemen1,2, Kornél Demeter1, Zsolt Borhegyi1, Éva Mikics1
1 Institute of Experimental Medicine, Budapest
2 Semmelweis University, Budapest

Text of the abstract

Introduction: Perinatal asphyxia (PA) represents is one of the leading causes of neonatal mortality and a significant contributor to long-lasting neuropsychiatric disorders and behavioral deficits. Targeted therapeutic possibilities are scarce and further limited by frequent cases of comorbidity with perinatal infections. Systemic inflammation increases vulnerability to CNS damage in the context of a hypoxic-ischaemic event, increasing the risk of cognitive disabilities on the long-term. Deciphering the neurobiological background of this sensitizing effect and developing targeted therapy is difficult on account of a lack of translationally relevant rodent models of PA. Pro-inflammatory cytokine IL-1 beta has been suggested to play key role in the pathophysiological cascades of both systemic inflammation and PA, as a possible contributor to the interactive effect leading to poor clinical outcome.

Aims: The objective of this study was to determine the long-term neuropsychiatric consequences of a mild asphyxia insult in inflammation-sensitized mice.

Methods: Male C57BL/6 mice pups received sequential s.c. IL-1 beta injections and/or a non-invasive asphyxia insult in normothermic conditions. Long-term behavioral outcome was assessed extensively by successive testing in an automated home cage training system (ATS) and IntelliCage System (IC). Thereafter, the animals took part in a wide range of behavioural tests for emotional and social profiling.

Results: While single-hit challenges of IL-1 or PA alone did not cause notable cognitive impairment, they showed significant conjoint effect on attention, impulse control and operant learning abilities in the ATS, while IC data indicated decreased spatial learning and cognitive flexibility in the double-hit (IL-1 + PA) group. Both groups subjected to PA showed higher anxiety scores in the open field and elevated plus maze and decreased sociability.

Conclusion: These results suggest that prior systemic inflammation sensitizes higher order emotionality and cognitive function-related brain areas to a mild PA insult, with a possible role of IL-1 beta in their synergistic negative effect on long-lasting neuropsychiatric sequelae.

Funding: This study was supported by the National Laboratory of Translational Neuroscience (Grant# RRF-2.3.1-21-2022-00011) and the National Research, Development and Innovation Office (Grant# K135292).