Sarkisova K Y, Gabova A V
Institute of Higher Nervous Activity and Neurophysiology Russian Academy of Sciences, Moscow, Russia.
Genes Brain Behav. 2018 Sep;17(7):e12477. doi: 10.1111/gbb.12477. Epub 2018 Apr 30.
WAG/Rij rats, a genetic animal model of absence epilepsy with comorbidity of depression, exhibit behavioral depression-like symptoms and spontaneous generalized spike-wave discharges (SWDs) in the EEG at the age of 6 to 8 months. The aim of the present study was to test the hypothesis that maternal care is an environmental factor which, along with genetic predisposition, may contribute to the expression of absence seizures and depression-like comorbidity later in life. To achieve this, a cross-fostering procedure was used. EEG and behavior in the forced swimming test were analyzed in WAG/Rij and Wistar offspring reared by their own mothers (non-cross-fostered), foster mothers of the same strain (in-fostered) or another strain (cross-fostered) at the age of 7 to 8 months. Maternal care and forced swimming test behavior were assessed in the dams. WAG/Rij mothers showed depression-like behavior and reduced maternal care irrespective of litter size and litter composition (own or foster pups) compared with Wistar dams. WAG/Rij offspring reared by Wistar dams with a high level of maternal care exhibited less and shorter SWDs and reduced depression-like comorbidity in adulthood compared with age-matched WAG/Rij offspring reared by their own or foster WAG/Rij mothers with a low level of maternal care. Moreover, rearing by Wistar mothers delayed the onset of absence epilepsy in WAG/Rij rats. Adoption by WAG/Rij dams did not change EEG and behavior in Wistar rats. Our study demonstrates that improvement of early care-giving environment can be used as a disease-modifying treatment to counteract epileptogenesis and behavioral comorbidities in genetic absence epilepsy.
WAG/Rij大鼠是一种伴有抑郁症共病的失神癫痫的遗传动物模型，在6至8个月大时表现出行为性抑郁样症状以及脑电图中的自发性全身性棘波-慢波放电（SWDs）。本研究的目的是检验以下假设：母亲的照料是一种环境因素，它与遗传易感性一起，可能导致日后生活中失神发作和抑郁样共病的表现。为了实现这一目标，采用了交叉寄养程序。对7至8个月大的由自己母亲抚养（非交叉寄养）、同品系的养母抚养（品系内寄养）或另一品系的养母抚养（交叉寄养）的WAG/Rij和Wistar后代进行了脑电图和强迫游泳试验中的行为分析。对母鼠的母性照料和强迫游泳试验行为进行了评估。与Wistar母鼠相比，WAG/Rij母鼠无论产仔大小和产仔组成（亲生或寄养幼崽）如何，均表现出抑郁样行为且母性照料减少。与由母性照料水平低的亲生或寄养WAG/Rij母亲抚养的年龄匹配的WAG/Rij后代相比，由母性照料水平高的Wistar母鼠抚养的WAG/Rij后代在成年期表现出较少且较短的SWDs，抑郁样共病也减少。此外，由Wistar母亲抚养可延迟WAG/Rij大鼠失神癫痫的发作。被WAG/Rij母鼠收养并未改变Wistar大鼠的脑电图和行为。我们的研究表明，改善早期照料环境可作为一种疾病修饰治疗方法，以对抗遗传性失神癫痫中的癫痫发生和行为共病。
