Environmental enrichment intervention for Rett syndrome: an individually randomised stepped wedge trial.
Environmental enrichment intervention for Rett syndrome: an individually randomised stepped wedge trial.
复制标题
DOI：
10.1186/s13023-017-0752-8
复制
发表时间：
2018-01-10
影响因子：
3.7
通讯作者：
Leonard H
中科院分区：
文献类型：
--
作者：
Downs J;Rodger J;Li C;Tan X;Hu N;Wong K;de Klerk N;Leonard H
Rett综合征是由MECP 2基因中的致病性突变引起的，对运动和认知发育具有重大影响。受损的MECP 2功能的影响之一是脑源性神经营养因子（BDNF）的产生减少，BDNF是正常神经元发育所需的蛋白质。当被安置在一个丰富的环境中时，MECP 2基因缺失的小鼠改善了运动能力，并增加了大脑中BDNF的水平。我们调查了环境丰富对Rett综合征女孩的粗大运动技能和血液BDNF水平的影响。一个由12名MECP 2突变且年龄小于6岁的女孩组成的遗传可变组参加了一项改良的个体随机阶梯楔形设计研究。进行了五次评估，两次在基线期，三次在干预期。使用Rett综合征粗大运动量表（最高评分为45分）对粗大运动功能进行了五次评估，两次在基线期，三次在干预期。在两次基线评估和干预期结束时测量BDNF的血液水平。干预措施包括运动学习和锻炼，并在六个月内补充社交，认知和其他感官体验。首次评估时，儿童的平均（SD）年龄为3岁（1岁1个月），范围为1岁6个月至5岁2个月。同样在基线时，平均（SD）粗大运动评分和血液BDNF水平分别为22.7/45（9.6）和165.0（28.8）ng/ml。调整协变量后，丰富的环境与治疗6个月后的大运动技能改善（系数8.2，95%CI 5.1，11.2）和血液BDNF水平增加321.4 ng/ml（95%CI 272.0，370.8）相关。生长、睡眠质量和情绪不受影响。行为干预，如环境丰富，可以减少Rett综合征的功能缺陷，有助于管理和进一步了解表观遗传机制的证据基础。环境富集将是一个重要的辅助评估新的药物疗法，使用BDNF途径，因为对加强突触和改善功能的影响。ACTRN12615001286538。
Rett syndrome is caused by a pathogenic mutation in the MECP2 gene with major consequences for motor and cognitive development. One of the effects of impaired MECP2 function is reduced production of Brain Derived Neurotrophic Factor (BDNF), a protein required for normal neuronal development. When housed in an enriched environment, MECP2 null mice improved motor abilities and increased levels of BDNF in the brain. We investigated the effects of environmental enrichment on gross motor skills and blood BDNF levels in girls with Rett syndrome. A genetically variable group of 12 girls with a MECP2 mutation and younger than 6 years participated in a modified individually randomised stepped wedge design study. Assessments were conducted on five occasions, two during the baseline period and three during the intervention period. Gross motor function was assessed using the Rett Syndrome Gross Motor Scale (maximum score of 45) on five occasions, two during the baseline period and three during the intervention period. Blood levels of BDNF were measured at the two baseline assessments and at the end of the intervention period. The intervention comprised motor learning and exercise supplemented with social, cognitive and other sensory experiences over a six-month period. At the first assessment, the mean (SD) age of the children was 3 years (1 year 1 month) years ranging from 1 year 6 months to 5 years 2 months. Also at baseline, mean (SD) gross motor scores and blood BDNF levels were 22.7/45 (9.6) and 165.0 (28.8) ng/ml respectively. Adjusting for covariates, the enriched environment was associated with improved gross motor skills (coefficient 8.2, 95%CI 5.1, 11.2) and a 321.4 ng/ml (95%CI 272.0, 370.8) increase in blood BDNF levels after 6 months of treatment. Growth, sleep quality and mood were unaffected. Behavioural interventions such as environmental enrichment can reduce the functional deficit in Rett syndrome, contributing to the evidence-base for management and further understanding of epigenetic mechanisms. Environmental enrichment will be an important adjunct in the evaluation of new drug therapies that use BDNF pathways because of implications for the strengthening of synapses and improved functioning. ACTRN12615001286538.
登录
查看更多内容
DOI：
10.1073/pnas.1311141111
发表时间：
2014-03-25
影响因子：
11.1
作者：
Khwaja, Omar S.;Ho, Eugenia;Kaufmann, Walter E.
通讯作者：
Kaufmann, Walter E.
DOI：
10.1186/1742-4933-7-2
发表时间：
2010-01-25
期刊：
Immunity & ageing : I & A
影响因子：
--
作者：
Dogliotti, Giada;Galliera, Emanuela;Corsi, Massimiliano M
通讯作者：
Corsi, Massimiliano M
影响因子：
1.9
作者：
Fehr, Stephanie;Bebbington, Ami;Downs, Jenny
通讯作者：
Downs, Jenny
影响因子：
9.9
作者：
Bebbington, A.;Anderson, A.;Leonard, H.
通讯作者：
Leonard, H.
影响因子：
4
作者：
Cuddapah VA;Pillai RB;Shekar KV;Lane JB;Motil KJ;Skinner SA;Tarquinio DC;Glaze DG;McGwin G;Kaufmann WE;Percy AK;Neul JL;Olsen ML
通讯作者：
Olsen ML