van Wijk N, Rijntjes E, van de Heijning B J M
Human and Animal Physiology Group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
Exp Physiol. 2008 Nov;93(11):1199-209. doi: 10.1113/expphysiol.2008.042416. Epub 2008 Jun 20.
A lack of thyroid hormone, i.e. hypothyroidism, during early development results in multiple morphological and functional alterations in the developing brain. In the present study, behavioural effects of perinatal and chronic hypothyroidism were assessed during development in both male and female offspring of hypothyroid rats. To induce hypothyroidism, dams and offspring were fed an iodide-poor diet and drinking water with 0.75% sodium perchlorate; dams starting 2 weeks prior to mating and pups either until the day of killing (chronic hypothyroidism) or only until weaning (perinatal hypothyroidism) to test for reversibility of the effects observed. Neuromotor competence, locomotor activity and cognitive function were monitored in the offspring until postnatal day 71 and were compared with age-matched control rats. Early neuromotor competence, as assessed in the grip test and balance beam test, was impaired by both chronic and perinatal hypothyroidism. The open field test, assessing locomotor activity, revealed hyperactive locomotor behavioural patterns in chronic hypothyroid animals only. The Morris water maze test, used to assess cognitive performance, showed that chronic hypothyroidism affected spatial memory in a negative manner. In contrast, perinatal hypothyroidism was found to impair spatial memory in female rats only. In general, the effects of chronic hypothyroidism on development were more pronounced than the effects of perinatal hypothyroidism, suggesting the early effects of hypothyroidism on functional alterations of the developing brain to be partly reversible and to depend on developmental timing of the deficiency.
在早期发育过程中缺乏甲状腺激素，即甲状腺功能减退，会导致发育中的大脑出现多种形态和功能改变。在本研究中，对甲状腺功能减退大鼠的雄性和雌性后代在发育过程中围产期和慢性甲状腺功能减退的行为影响进行了评估。为诱导甲状腺功能减退，给母鼠和幼崽喂食低碘饮食并饮用含0.75%高氯酸钠的水；母鼠在交配前2周开始，幼崽则要么一直持续到处死当天（慢性甲状腺功能减退），要么只持续到断奶（围产期甲状腺功能减退），以测试所观察到的影响的可逆性。在后代出生后第71天之前监测其神经运动能力、运动活动和认知功能，并与年龄匹配的对照大鼠进行比较。通过抓握试验和平衡木试验评估的早期神经运动能力，在慢性和围产期甲状腺功能减退的情况下均受损。评估运动活动的旷场试验显示，只有慢性甲状腺功能减退的动物出现运动行为亢进模式。用于评估认知表现的莫里斯水迷宫试验表明，慢性甲状腺功能减退对空间记忆有负面影响。相比之下，发现围产期甲状腺功能减退仅损害雌性大鼠的空间记忆。总体而言，慢性甲状腺功能减退对发育的影响比围产期甲状腺功能减退的影响更明显，这表明甲状腺功能减退对发育中大脑功能改变的早期影响部分是可逆的，并且取决于缺乏的发育时间。
