Sex-specific Developmental Differences of Flurothyl-induced Early Life Seizures on Learning and Memory in Rats
Abstract number :
2.511
Submission category :
1. Basic Mechanisms / 1A. Epileptogenesis of acquired epilepsies
Year :
2024
Submission ID :
1407
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Andrea Grigelova, MSc. – Institute of Physiology CAS
Alex Kratina, MSc. – Institute of Physiology, CAS
Anna Mikulecka, RNDr, PhD – Institute of Physiology CAS
Hana Kubova, PharmD, PhD, DSc – Institute of Physiology CAS
Rationale: Early life seizures (ELS) are linked to an increased risk of developing epilepsy and other adverse neurodevelopmental outcomes. Research using laboratory rodents indicates that ELS can lead to enduring behavioral changes in adulthood. Given the known sexual dimorphism in brain development, it is plausible that ELS may affect immature males and females differently. However, the impact of sex on the progression, pattern, and severity of these behavioral changes has been only partially studied.
Methods: From postnatal day 6 (P6) to P10, male and female Wistar rats were exposed 5x per day to flurothyl (FLU), inducing recurrent generalized tonic-clonic seizures. Body weights were recorded daily until weaning at P28. From P12 onward, a series of age-appropriate behavioral tests were performed to assess sex-, age-, and treatment-related changes across various behavioral domains (see Image 1). The Morris Water Maze (MWM) was used to evaluate the impact of ELS and previous testing experience on spatial learning and memory functions. Three groups of animals with different experience were tested at different ages in the MWM across three separate sessions: Group 1 - animals subjected to all behavioral tests (P47-P51); Group 2 - animals subjected to all behavioral tests except 1st session of MWM (P90-P94); Group 3 - animals naive to testing, subjected only to 3rd session of MWM (P137-P141).
Results: The impact of ELS on behavioral parameters varied by sex and age. MWM results indicated that ELS had a more pronounced effect on learning and memory retention in female rats. FLU-exposed female rats showed increased difficulty in locating the hidden platform, suggesting impaired spatial learning or the adoption of alternative strategies. FLU-exposed rats also spent significantly more time engaging in thigmotaxis, rather than directly navigating to the platform. Additionally, both control and FLU-exposed female rats exhibited higher overall activity levels compared to males, covering longer distances during tests. Previous experience with testing improved memory retention in MWM.
Conclusions: Our findings suggest that ELS impair cognitive functions differently in females and in animals naïve to previous testing, highlighting the influence of sex and cognitive stimulation in shaping behavior related to learning and memory formation/retention. These findings underscore the importance of considering sex differences in the assessment of neurodevelopmental outcomes following ELS and suggest that female rats may be more affected. This highlights the need for incorporating sex differences into ELS research and intervention strategies.
Funding: Supported by grant 23-05274S from the Czech Science Foundation, the National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107, co-supported by the EU), and Research Project RVO 67985823.
Basic Mechanisms