Neurometabolite mapping highlights elevated myo-inositol profiles within the developing brain in down syndrome.
Neurometabolite mapping highlights elevated myo-inositol profiles within the developing brain in down syndrome.
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神经代谢物图谱突出显示唐氏综合症患者发育中大脑内肌醇含量升高。
DOI：
10.1016/j.nbd.2021.105316
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发表时间：
2021-06
影响因子：
6.1
通讯作者：
De Vita E
中科院分区：
文献类型：
--
作者：
Patkee PA;Baburamani AA;Long KR;Dimitrova R;Ciarrusta J;Allsop J;Hughes E;Kangas J;McAlonan GM;Rutherford MA;De Vita E
唐氏综合征（DS）或21三体的神经发育表型是可变的，包括广泛的认知障碍和早发性阿尔茨海默病（AD）的高风险。在DS中，脑内感兴趣的关键代谢物是肌醇（mIns）。NA+/mIns共转运蛋白位于人21号染色体上，在DS中过表达。在DS成人中，脑mIns升高先前与认知障碍相关，并被认为是进展为AD的风险标志物。然而，目前尚不清楚大脑mIns是否在发育早期增加。本研究的目的是估计DS和年龄匹配对照组发育中大脑中的mIns浓度水平和关键脑代谢物[N-乙酰天冬氨酸（NAA）、胆碱（Cho）和肌酸（Cr）]。我们在新生儿DS（n = 12）和年龄匹配的对照组（n = 26）出生后（月经后36-45周）扫描体内磁共振波谱（MRS）。此外，我们在早期（受孕后10-20周）离体胎儿脑组织样品中使用质谱法，这些样品来自DS（n = 14）和对照（n = 30）病例。相对于[Cho]和[Cr]，我们报告称，与年龄匹配的典型发育对照组相比，DS新生儿体内基底神经节/丘脑中[mIns]的比例升高。甘氨酸浓度比[Gly]/[Cr]和[Cho]/[Cr]也出现升高。与对照组相比，我们观察到DS的离体胎仔皮质脑组织中[mIns]升高。总之，早在受孕后10周，大脑mIns的水平就明显较高，并且从月经后36周开始可以在体内测量。未来的工作将确定代谢物的这种早期差异是否与儿童期的认知结果有关，或者是否可作为早期干预的潜在治疗生物标志物。胎儿皮质DS脑中肌醇升高。在新生儿DS脑使用MR波谱检测到升高的肌醇。DS新生儿脑中也存在胆碱/肌酸和甘氨酸/肌酸升高。
The neurodevelopmental phenotype in Down Syndrome (DS), or Trisomy 21, is variable including a wide spectrum of cognitive impairment and a high risk of early-onset Alzheimer's disease (AD). A key metabolite of interest within the brain in DS is Myo-inositol (mIns). The NA+/mIns co-transporter is located on human chromosome 21 and is overexpressed in DS. In adults with DS, elevated brain mIns was previously associated with cognitive impairment and proposed as a risk marker for progression to AD. However, it is unknown if brain mIns is increased earlier in development. The aim of this study was to estimate mIns concentration levels and key brain metabolites [N-acetylaspartate (NAA), Choline (Cho) and Creatine (Cr)] in the developing brain in DS and aged-matched controls. We used in vivo magnetic resonance spectroscopy (MRS) in neonates with DS (n = 12) and age-matched controls (n = 26) scanned just after birth (36–45 weeks postmenstrual age). Moreover, we used Mass Spectrometry in early (10–20 weeks post conception) ex vivo fetal brain tissue samples from DS (n = 14) and control (n = 30) cases. Relative to [Cho] and [Cr], we report elevated ratios of [mIns] in vivo in the basal ganglia/thalamus, in neonates with DS, when compared to age-matched typically developing controls. Glycine concentration ratios [Gly]/[Cr] and [Cho]/[Cr] also appear elevated. We observed elevated [mIns] in the ex vivo fetal cortical brain tissue in DS compared with controls. In conclusion, a higher level of brain mIns was evident as early as 10 weeks post conception and was measurable in vivo from 36 weeks post-menstrual age. Future work will determine if this early difference in metabolites is linked to cognitive outcomes in childhood or has utility as a potential treatment biomarker for early intervention. Myo-inositol is elevated in fetal cortical DS brain. Elevated myo-inositol was detected in the neonatal DS brain using MR spectroscopy. Elevated Choline/Creatine and Glycine/Creatine was also present in DS neonatal brain.
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影响因子：
3.7
作者：
Fenili D;Weng YQ;Aubert I;Nitz M;McLaurin J
通讯作者：
McLaurin J
影响因子：
3.3
作者：
Girard, N;Fogliarini, C;Cozzone, P
通讯作者：
Cozzone, P
DOI：
10.1073/pnas.1606348113
发表时间：
2016-06-07
影响因子：
11.1
作者：
Dai, Gucan;Yu, Haijie;Hille, Bertil
通讯作者：
Hille, Bertil
影响因子：
3.3
作者：
Kim, H;Thompson, RB;Allen, PS
通讯作者：
Allen, PS
影响因子：
3.5
作者：
Evangelou, I. E.;du Plessis, A. J.;Limperopoulos, C.
通讯作者：
Limperopoulos, C.