Transcriptomic analysis reveals distinct adaptive molecular mechanism in the hippocampal CA3 from rats susceptible or not-susceptible to hyperthermia-induced seizures

Transcriptomic analysis reveals distinct adaptive molecular mechanism in the hippocampal CA3 from rats susceptible or not-susceptible to hyperthermia-induced seizures

Febrile seizures during early childhood are a relevant risk factor for the development of mesial temporal lobe epilepsy. Nevertheless, the molecular mechanism induced by febrile seizures that render the brain susceptible or not-susceptible to epileptogenesis remain poorly understood. Because the tem...

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Bibliographic Details
Published in:Scientific reports Vol. 13; no. 1; p. 10265
Main Authors: Bando, Silvia Y., Bertonha, Fernanda B., Menezes, Pedro H. N., Takahara, André K., Khaled, Nathália A., Santos, Paula, S. Junqueira, Mara, Cesar, Roberto M., Moreira-Filho, Carlos A.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 24-06-2023
Nature Publishing Group
Nature Portfolio
Subjects:
692/617/375
692/617/375/178
Animal models
Animals
Child, Preschool
Children
Convulsions & seizures
Disease Susceptibility
Epilepsy
Hippocampus
Humanities and Social Sciences
Humans
Hyperthermia
Hyperthermia, Induced
Immune response
Inflammation
MicroRNAs
MicroRNAs - genetics
miRNA
Molecular modelling
multidisciplinary
Neurogenesis
Rats
Risk factors
Science
Science (multidisciplinary)
Seizures
Seizures, Febrile - genetics
Temporal lobe
Therapeutic targets
Transcriptome
Transcriptomics
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Summary:Febrile seizures during early childhood are a relevant risk factor for the development of mesial temporal lobe epilepsy. Nevertheless, the molecular mechanism induced by febrile seizures that render the brain susceptible or not-susceptible to epileptogenesis remain poorly understood. Because the temporal investigation of such mechanisms in human patients is impossible, rat models of hyperthermia-induced febrile seizures have been used for that purpose. Here we conducted a temporal analysis of the transcriptomic and microRNA changes in the ventral CA3 of rats that develop (HS group) or not-develop (HNS group) seizures after hyperthermic insult on the eleventh postnatal day. The selected time intervals corresponded to acute, latent, and chronic phases of the disease. We found that the transcriptional differences between the HS and the HNS groups are related to inflammatory pathways, immune response, neurogenesis, and dendritogenesis in the latent and chronic phases. Additionally, the HNS group expressed a greater number of miRNAs (some abundantly expressed) as compared to the HS group. These results indicate that HNS rats were able to modulate their inflammatory response after insult, thus presenting better tissue repair and re-adaptation. Potential therapeutic targets, including genes, miRNAs and signaling pathways involved in epileptogenesis were identified.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-37535-w