Sex differences in the developing brain impact stress-induced epileptogenicity following hyperthermia-induced seizures

Febrile seizures (FS) are common, affecting 2–5% of children between the ages of 3 months and 6 years. Complex FS occur in 10% of patients with FS and are strongly associated with mesial temporal lobe epilepsy. Current research suggests that predisposing factors, such as genetic and anatomic abnorma...

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Autores principales:	Daniele C. Wolf, Sébastien Desgent, Nathalie T. Sanon, Jia-Shu Chen, Lior M. Elkaim, Ciprian M. Bosoi, Patricia N. Awad, Alexe Simard, Muhammad T. Salam, Guillaume-Alexandre Bilodeau, Sandra Duss, Mohamad Sawan, Evan C. Lewis, Alexander G. Weil
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Sex differences Corticosterone Chronic stress Febrile seizures SHRP HPA Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/8731fe1d9396495487d22402c263a09b
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spelling	oai:doaj.org-article:8731fe1d9396495487d22402c263a09b2021-12-04T04:33:11ZSex differences in the developing brain impact stress-induced epileptogenicity following hyperthermia-induced seizures1095-953X10.1016/j.nbd.2021.105546https://doaj.org/article/8731fe1d9396495487d22402c263a09b2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0969996121002953https://doaj.org/toc/1095-953XFebrile seizures (FS) are common, affecting 2–5% of children between the ages of 3 months and 6 years. Complex FS occur in 10% of patients with FS and are strongly associated with mesial temporal lobe epilepsy. Current research suggests that predisposing factors, such as genetic and anatomic abnormalities, may be necessary for complex FS to translate to mesial temporal lobe epilepsy. Sex hormones are known to influence seizure susceptibility and epileptogenesis, but whether sex-specific effects of early life stress play a role in epileptogenesis is unclear. Here, we investigate sex differences in the activity of the hypothalamic–pituitary–adrenal (HPA) axis following chronic stress and the underlying contributions of gonadal hormones to the susceptibility of hyperthermia-induced seizures (HS) in rat pups. Chronic stress consisted of daily injections of 40 mg/kg of corticosterone (CORT) subcutaneously from postnatal day (P) 1 to P9 in male and female rat pups followed by HS at P10. Body mass, plasma CORT levels, temperature threshold to HS, seizure characteristics, and electroencephalographic in vivo recordings were compared between CORT- and vehicle (VEH)-injected littermates during and after HS at P10. In juvenile rats (P18-P22), in vitro CA1 pyramidal cell recordings were recorded in males to investigate excitatory and inhibitory neuronal circuits. Results show that daily CORT injections increased basal plasma CORT levels before HS and significantly reduced weight gain and body temperature threshold of HS in both males and females. CORT also significantly lowered the generalized convulsions (GC) latency while increasing recovery time and the number of electrographic seizures (>10s), which had longer duration. Furthermore, sex-specific differences were found in response to chronic CORT injections. Compared to females, male pups had increased basal plasma CORT levels after HS, longer recovery time and a higher number of electrographic seizures (>10s), which also had longer duration. Sex-specific differences were also found at baseline conditions with lower latency to generalized convulsions and longer duration of electrographic seizures in males but not in females. In juvenile male rats, the amplitude of evoked excitatory postsynaptic potentials, as well as the amplitude of inhibitory postsynaptic currents, were significantly greater in CORT rats when compared to VEH littermates. These findings not only validate CORT injections as a stress model, but also show a sex difference in baseline conditions as well as a response to chronic CORT and an impact on seizure susceptibility, supporting a potential link between sustained early-life stress and complex FS. Overall, these effects also indicate a putatively less severe phenotype in female than male pups. Ultimately, studies investigating the biological underpinnings of sex differences as a determining factor in mental and neurologic problems are necessary to develop better diagnostic, preventative, and therapeutic approaches for all patients regardless of their sex.Daniele C. WolfSébastien DesgentNathalie T. SanonJia-Shu ChenLior M. ElkaimCiprian M. BosoiPatricia N. AwadAlexe SimardMuhammad T. SalamGuillaume-Alexandre BilodeauSandra DussMohamad SawanEvan C. LewisAlexander G. WeilElsevierarticleSex differencesCorticosteroneChronic stressFebrile seizuresSHRPHPANeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENNeurobiology of Disease, Vol 161, Iss , Pp 105546- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Sex differences Corticosterone Chronic stress Febrile seizures SHRP HPA Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Sex differences Corticosterone Chronic stress Febrile seizures SHRP HPA Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Daniele C. Wolf Sébastien Desgent Nathalie T. Sanon Jia-Shu Chen Lior M. Elkaim Ciprian M. Bosoi Patricia N. Awad Alexe Simard Muhammad T. Salam Guillaume-Alexandre Bilodeau Sandra Duss Mohamad Sawan Evan C. Lewis Alexander G. Weil Sex differences in the developing brain impact stress-induced epileptogenicity following hyperthermia-induced seizures
description	Febrile seizures (FS) are common, affecting 2–5% of children between the ages of 3 months and 6 years. Complex FS occur in 10% of patients with FS and are strongly associated with mesial temporal lobe epilepsy. Current research suggests that predisposing factors, such as genetic and anatomic abnormalities, may be necessary for complex FS to translate to mesial temporal lobe epilepsy. Sex hormones are known to influence seizure susceptibility and epileptogenesis, but whether sex-specific effects of early life stress play a role in epileptogenesis is unclear. Here, we investigate sex differences in the activity of the hypothalamic–pituitary–adrenal (HPA) axis following chronic stress and the underlying contributions of gonadal hormones to the susceptibility of hyperthermia-induced seizures (HS) in rat pups. Chronic stress consisted of daily injections of 40 mg/kg of corticosterone (CORT) subcutaneously from postnatal day (P) 1 to P9 in male and female rat pups followed by HS at P10. Body mass, plasma CORT levels, temperature threshold to HS, seizure characteristics, and electroencephalographic in vivo recordings were compared between CORT- and vehicle (VEH)-injected littermates during and after HS at P10. In juvenile rats (P18-P22), in vitro CA1 pyramidal cell recordings were recorded in males to investigate excitatory and inhibitory neuronal circuits. Results show that daily CORT injections increased basal plasma CORT levels before HS and significantly reduced weight gain and body temperature threshold of HS in both males and females. CORT also significantly lowered the generalized convulsions (GC) latency while increasing recovery time and the number of electrographic seizures (>10s), which had longer duration. Furthermore, sex-specific differences were found in response to chronic CORT injections. Compared to females, male pups had increased basal plasma CORT levels after HS, longer recovery time and a higher number of electrographic seizures (>10s), which also had longer duration. Sex-specific differences were also found at baseline conditions with lower latency to generalized convulsions and longer duration of electrographic seizures in males but not in females. In juvenile male rats, the amplitude of evoked excitatory postsynaptic potentials, as well as the amplitude of inhibitory postsynaptic currents, were significantly greater in CORT rats when compared to VEH littermates. These findings not only validate CORT injections as a stress model, but also show a sex difference in baseline conditions as well as a response to chronic CORT and an impact on seizure susceptibility, supporting a potential link between sustained early-life stress and complex FS. Overall, these effects also indicate a putatively less severe phenotype in female than male pups. Ultimately, studies investigating the biological underpinnings of sex differences as a determining factor in mental and neurologic problems are necessary to develop better diagnostic, preventative, and therapeutic approaches for all patients regardless of their sex.
format	article
author	Daniele C. Wolf Sébastien Desgent Nathalie T. Sanon Jia-Shu Chen Lior M. Elkaim Ciprian M. Bosoi Patricia N. Awad Alexe Simard Muhammad T. Salam Guillaume-Alexandre Bilodeau Sandra Duss Mohamad Sawan Evan C. Lewis Alexander G. Weil
author_facet	Daniele C. Wolf Sébastien Desgent Nathalie T. Sanon Jia-Shu Chen Lior M. Elkaim Ciprian M. Bosoi Patricia N. Awad Alexe Simard Muhammad T. Salam Guillaume-Alexandre Bilodeau Sandra Duss Mohamad Sawan Evan C. Lewis Alexander G. Weil
author_sort	Daniele C. Wolf
title	Sex differences in the developing brain impact stress-induced epileptogenicity following hyperthermia-induced seizures
title_short	Sex differences in the developing brain impact stress-induced epileptogenicity following hyperthermia-induced seizures
title_full	Sex differences in the developing brain impact stress-induced epileptogenicity following hyperthermia-induced seizures
title_fullStr	Sex differences in the developing brain impact stress-induced epileptogenicity following hyperthermia-induced seizures
title_full_unstemmed	Sex differences in the developing brain impact stress-induced epileptogenicity following hyperthermia-induced seizures
title_sort	sex differences in the developing brain impact stress-induced epileptogenicity following hyperthermia-induced seizures
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/8731fe1d9396495487d22402c263a09b
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Sex differences in the developing brain impact stress-induced epileptogenicity following hyperthermia-induced seizures

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