Hyperthermia-induced seizures followed by repetitive stress are associated with age-dependent changes in specific aspects of the mouse stress system

Author(s)

Umeoka, Eduardo H. L. ^{[1, 2]} ; Robinson, Edward J. ^{[1, 3]} ; Turimella, Sada Lakshmi ^[1] ; van Campen, Jolien S. ^{[1, 4]} ; Motta-Teixeira, Livia C. ^[5] ; Sarabdjitsingh, R. Angela ^[1] ; Garcia-Cairasco, Norberto ^{[2, 6]} ; Braun, Kees ^[4] ; de Graan, Pierre N. ^[1] ; Joels, Marian ^{[1, 7]}

Affiliation

^[1] Univ Utrecht, Dept Translat Neurosci, Brain Ctr Rudolf Magnus, Univ Med Ctr Utrecht, Utrecht - Netherlands

^[2] Univ Sao Paulo, Neurosci & Behav Sci Dept, Ribeirao Preto Sch Med, Ribeirao Preto, SP - Brazil

^[3] Univ Amsterdam, Swammerdam Inst Life Sci, Amsterdam - Netherlands

^[4] Univ Med Ctr Utrecht, Dept Pediat Neurol, Brain Ctr Rudolf Magnus, Utrecht - Netherlands

^[5] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Physiol Dept, Ribeirao Preto Sch Med, Ribeirao Preto, SP - Brazil

^[7] Univ Groningen, Univ Med Ctr Groningen, Groningen - Netherlands

• Document type: Journal article
• Source: Journal of Neuroendocrinology; v. 31, n. 4 APR 2019.
• Web of Science Citations: 1

Abstract

Stress is among the most frequently self-reported factors provoking epileptic seizures in children and adults. It is still unclear, however, why some people display stress-sensitive seizures and others do not. Recently, we showed that young epilepsy patients with stress-sensitive seizures exhibit a dysregulated hypothalamic-pituitary-adrenal (HPA)-axis. Most likely, this dysregulation gradually develops, and is triggered by stressors occurring early in life (early-life stress {[}ELS]). ELS may be particularly impactful when overlapping with the period of epileptogenesis. To examine this in a controlled and prospective manner, the present study investigated the effect of repetitive variable stressors or control treatment between postnatal day (PND) 12 and 24 in male mice exposed on PND10 to hyperthermia (HT)-induced prolonged seizures (control: normothermia). A number of peripheral and central indices of HPA-axis activity were evaluated at pre-adolescent and young adult age (ie, at PND25 and 90, respectively). At PND25 but not at PND90, body weight gain and absolute as well as relative (to body weight) thymus weight were reduced by ELS (vs control), whereas relative adrenal weight was enhanced, confirming the effectiveness of the stress treatment. Basal and stress-induced corticosterone levels were unaffected, though, by ELS at both ages. HT by itself did not affect any of these peripheral markers of HPA-axis activity, nor did it interact with ELS. However, centrally we did observe age-specific interaction effects of HT and ELS with regard to hippocampal glucocorticoid receptor mRNA expression, neurogenesis with the immature neurone marker doublecortin and the number of hilar (ectopic) granule cells using Prox1 staining. This lends some support to the notion that exposure to repetitive stress after HT-induced seizures may dysregulate central components of the stress system in an age-dependent manner. Such dysregulation could be one of the mechanisms conferring higher vulnerability of individuals with epilepsy to develop seizures in the face of stress. (AU)

• FAPESP's process: 16/18941-4 - Effects of maternal melatonin deprivation during pregnancy and lactation on the offspring neuroimmune system
• Grantee: Lívia Clemente Motta Teixeira
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 11/13412-0 - Behavioral and morphologic characterization related to hypothalamic-pituitary-adrenal (HPA) axis activity in Wistar audiogenic rats after chronic seizures
• Grantee: Eduardo Henrique de Lima Umeoka
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/21401-0 - Effect of multiple stresses during early-life on hyperthermia-induced epileptogenesis in young and adult mice
• Grantee: Eduardo Henrique de Lima Umeoka
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate