Sex Differences in Neurodevelopmental Outcome of Early Life Seizures in Rats
Abstract number :
3.063
Submission category :
1. Basic Mechanisms / 1F. Other
Year :
2023
Submission ID :
812
Source :
www.aesnet.org
Presentation date :
12/4/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Hana Kubova, PharmD – Institute of Physiology CAS
Anita Conti, PhD student – Institute of Physiology CAS; Alessandro Negri, PhD student – PhD student, Institute of Physiology CAS; Andrea Grigelova, PhD student – Institute of Physiology CAS; Anna Mikulecka, scientist – Institute of Physiology CAS
Rationale:
Seizures in newborns are associated with a high risk for subsequent epilepsy and adverse neurodevelopmental consequences. Studies in laboratory rodents demonstrate that seizures early in life can result in permanent behavioral abnormalities later in life, but dynamics of these changes as well as the role of sex in pattern and severity of behavioral alterations are examined only exceptionally.
Methods:
Starting at postnatal (P) day six Wistar rats of both sexes were exposed to flurothyl (FLU)-induced generalized tonic-clonic seizures (five seizures per day) for five consecutive days. Body weight was checked up to weaning and then before behavioral testing. Starting at P14, animals were submitted to battery of behavioral tests, selected according the level of maturation. The tests were performed in the following order: rotarod test (P18) - rotarod performance test (P23) - elevated plus maze (P25) - open field test (P30). As adults the same animals were tested in the open field test (P57), elevated plus maze (P59), and Morris water maze (P63 to P74).
Results:
Early life seizures resulted in growth retardation in both sexes. FLU-exposed animals gained significantly less weight up to P11. Mortality was 5% with no difference between males and females. Effects of early-life seizures on behavioral parameters were significantly sex dependent and differences were detected in both juvenile (pre-pubescent) and adult animals. In the rotarod test, males experiencing early life seizures spent longer time on the bar compared to controls in the second test, no such difference was found in females. Interestingly, early life seizures resulted in increased anxiety in males who spent more time in closed arms of EPM in both tests performed in juvenile and adult rats, but not in females. On contrary, early life seizures impaired learning abilities in Morris water maze more in females than in males. Female rats also chose different strategy solving this task spending more time swimming around walls of the maze. In general, both control and FLU-exposed female rats were more active and they moved longer distances in all test.
Conclusions:
Our data show the role of sex in the neurobehavioral outcome of early-life seizures not only in sexually mature animals but also in juveniles. These results clearly demonstrate the necessity of studying impact of early brain insults at different developmental stages and in both sexes.
Funding:
Supported by grant 23-05274S of the Czech Science Foundation, project National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107) (co-supported by EU) and Research Project RVO 67985823.
Basic Mechanisms