PDF(Pubmed)
Abstract：
OBJECTIVE: Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild-intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams.
METHODS: Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 μg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated.
RESULTS: A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone.
CONCLUSIONS: Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.
METHODS: Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 μg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated.
RESULTS: A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone.
CONCLUSIONS: Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.
摘要：
目的：左旋甲状腺素（LEV）单药治疗不能完全改善甲状腺功能减退引起的认知和行为障碍，而运动和LEV的联合治疗可能会改善这些缺陷。这项研究旨在确定轻度强度的强迫运动和LEV治疗对甲状腺功能减退的男性后代的焦虑状况和认知功能的影响。
方法：将24只雌性大鼠随机分为假（健康）组和甲状腺功能减退组，然后与雄性大鼠交配。阴道斑块的存在证实怀孕（妊娠日，GD0）。6-丙基-2-硫氧嘧啶(PTU，从GD6到出生后第21天（PND），将100ppm）添加到甲状腺功能减退组的饮用水中。假手术组接受自来水。在PND21上，母亲的血清T4水平，和10只幼崽进行测量以确认甲状腺功能减退。将64只雄性幼崽静置30天，然后分为八组，分别接受生理盐水或LEV（50μg/kg，i.p.）有或没有强迫轻度强度运动。经过14天的干预，类似焦虑的行为，空间学习和记忆，评估海马脑源性神经营养因子（BDNF）水平。
结果：产前和产后PTU诱导的甲状腺功能减退模型增加了焦虑样行为，空间学习和记忆受损，雄性子代大鼠海马BDNF水平降低。LEV单独增加BDNF水平并改善空间学习。单靠运动就能增加BDNF水平,改善空间学习和记忆，减少了焦虑样的行为。与单独运动或LEV相比，运动加LEV更有效地改善了焦虑样行为和空间学习。
结论：实际上，这些临床前发现突出了运动和LEV方案联合治疗甲状腺功能亢进患者的重要性.
方法：将24只雌性大鼠随机分为假（健康）组和甲状腺功能减退组，然后与雄性大鼠交配。阴道斑块的存在证实怀孕（妊娠日，GD0）。6-丙基-2-硫氧嘧啶(PTU，从GD6到出生后第21天（PND），将100ppm）添加到甲状腺功能减退组的饮用水中。假手术组接受自来水。在PND21上，母亲的血清T4水平，和10只幼崽进行测量以确认甲状腺功能减退。将64只雄性幼崽静置30天，然后分为八组，分别接受生理盐水或LEV（50μg/kg，i.p.）有或没有强迫轻度强度运动。经过14天的干预，类似焦虑的行为，空间学习和记忆，评估海马脑源性神经营养因子（BDNF）水平。
结果：产前和产后PTU诱导的甲状腺功能减退模型增加了焦虑样行为，空间学习和记忆受损，雄性子代大鼠海马BDNF水平降低。LEV单独增加BDNF水平并改善空间学习。单靠运动就能增加BDNF水平,改善空间学习和记忆，减少了焦虑样的行为。与单独运动或LEV相比，运动加LEV更有效地改善了焦虑样行为和空间学习。
结论：实际上，这些临床前发现突出了运动和LEV方案联合治疗甲状腺功能亢进患者的重要性.
