Stanford John A, Shuler Jeffrey M, Fowler Stephen C, Stanford Kimberly G, Ma Delin, Bittel Douglas C, Le Pichon Jean-Baptiste, Shapiro Steven M
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas.
Department of Pharmacology and Toxicology, University of Kansas, Lawrence, Kansas.
Pediatr Res. 2015 Mar;77(3):434-9. doi: 10.1038/pr.2014.199. Epub 2014 Dec 17.
Neonatal jaundice resulting from elevated unconjugated bilirubin occurs in 60-80% of newborn infants. Although mild jaundice is generally considered harmless, little is known about its long-term consequences. Recent studies have linked mild bilirubin-induced neurological dysfunction (BIND) with a range of neurological syndromes, including attention-deficit hyperactivity disorder. The goal of this study was to measure BIND across the lifespan in the Gunn rat model of BIND.
Using a sensitive force plate actometer, we measured locomotor activity and gait in jaundiced (jj) Gunn rats versus their nonjaundiced (Nj) littermates. Data were analyzed for young adult (3-4 mo), early middle-aged (9-10 mo), and late middle-aged (17-20 mo) male rats.
jj rats exhibited lower body weights at all ages and a hyperactivity that resolved at 17-20 mo of age. Increased propulsive force and gait velocity accompanied hyperactivity during locomotor bouts at 9-10 mo in jj rats. Stride length did not differ between the two groups at this age. Hyperactivity normalized, and gait deficits, including decreased stride length, propulsive force, and gait velocity, emerged in the 17-20-mo-old jj rats.
These results demonstrate that, in aging, hyperactivity decreases with the onset of gait deficits in the Gunn rat model of BIND.
由未结合胆红素升高引起的新生儿黄疸发生在60%-80%的新生儿中。虽然轻度黄疸通常被认为无害,但其长期后果却鲜为人知。最近的研究将轻度胆红素诱导的神经功能障碍(BIND)与一系列神经综合征联系起来,包括注意力缺陷多动障碍。本研究的目的是在BIND的Gunn大鼠模型中测量其一生的BIND情况。
我们使用灵敏的测力板活动计,测量黄疸(jj)Gunn大鼠与其非黄疸(Nj)同窝仔鼠的运动活动和步态。对年轻成年(3-4个月)、中年早期(9-10个月)和中年晚期(17-20个月)的雄性大鼠的数据进行了分析。
jj大鼠在所有年龄段体重均较低,且在17-20个月龄时多动症状消失。在9-10个月大的jj大鼠运动期间,推进力和步态速度增加伴随着多动。此时两组大鼠的步长没有差异。多动症状恢复正常,而在17-20个月大的jj大鼠中出现了步态缺陷,包括步长、推进力和步态速度下降。
这些结果表明,在衰老过程中,BIND的Gunn大鼠模型中多动随着步态缺陷的出现而减少。