Postmortem Analyses in a Patient With Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD): II. Histological, Lipid, and Gene Expression Outcomes in Regional Brain Tissue.
Postmortem Analyses in a Patient With Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD): II. Histological, Lipid, and Gene Expression Outcomes in Regional Brain Tissue.
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DOI：
10.1177/0883073820987742
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发表时间：
2021-11
影响因子：
1.9
通讯作者：
SSADH Deficiency Investigators Consortium (SDIC)
中科院分区：
文献类型：
--
作者：
Walters DC;Lawrence R;Kirby T;Ahrendsen JT;Anderson MP;Roullet JB;Murphy EJ;Gibson KM;SSADH Deficiency Investigators Consortium (SDIC)
我们已经扩展了以前的代谢措施，在死后组织（额叶和顶叶，脑桥，小脑，海马，和大脑皮层），从一个37岁。患有琥珀酸半醛脱氢酶缺乏症（SSADHD）的男性患者死于SUDEP（癫痫原因不明的猝死）。固定皮质和海马的组织学特征显示轻度至中度星形胶质细胞增生，尤其是在白色物质中。对患者所有切片中总磷脂质量的分析显示，与（n=2-4）年龄大致匹配的对照组相比，皮质增加61%，海马减少51%。主要磷脂类的质量和摩尔组成的检查显示，富含髓鞘的磷脂减少，如磷脂酰丝氨酸，鞘磷脂和乙醇胺缩醛磷脂。基因表达评价（RT 2 Profiler PCR Arrays，GABA，谷氨酸; Qiagen）显示小脑、顶叶和额叶中14/15个GABAA受体亚单位失调，ε、θ、ρ1和ρ2亚单位下调最显著（7.7-9.9倍）。GABAB受体亚单位在很大程度上不受影响，离子型谷氨酸受体。代谢型谷氨酸受体6的表达持续下调（最大5.9倍），神经递质转运蛋白（GABA）成员13的表达也是如此（最大7.3倍）。对于其他基因，观察到白细胞介素1β（最大下调9.9倍）和突触核蛋白α（最大上调6.5倍）的一致失调。我们的数据为SSADHD脑功能提供了独特的见解，证实了先前在无效小鼠模型中观察到的星形胶质细胞增生和脂质异常，同时突出了对这种疾病中GABA能/谷氨酸能基因表达的长期影响。
We have extended previous metabolic measures in post-mortem tissues (frontal and parietal lobes, pons, cerebellum, hippocampus, and cerebral cortex) obtained from a 37 y.o. male patient with succinic semialdehyde dehydrogenase deficiency (SSADHD) who expired from SUDEP (sudden unexplained death in epilepsy). Histopathological characterization of fixed cortex and hippocampus revealed mild to moderate astrogliosis, especially in white matter. Analysis of total phospholipid mass in all sections of the patient revealed a 61% increase in cortex and 51% decrease in hippocampus as compared to (n=2–4) approximately age-matched controls. Examination of mass and molar composition of major phospholipid classes showed decreases in phospholipids enriched in myelin, such as phosphatidylserine, sphingomyelin, and ethanolamine plasmalogen. Evaluation of gene expression (RT2 Profiler PCR Arrays, GABA, glutamate; Qiagen) revealed dysregulation in 14/15 GABAA receptor subunits in cerebellum, parietal, and frontal lobes with the most significant down-regulation in ε, θ, ρ1 and ρ2 subunits (7.7–9.9-fold). GABAB receptor subunits were largely unaffected, as were ionotropic glutamate receptors. The metabotropic glutamate receptor 6 was consistently down-regulated (maximum 5.9-fold) as was the neurotransmitter transporter (GABA), member 13 (maximum 7.3-fold). For other genes, consistent dysregulation was seen for interleukin 1β (maximum down-regulation 9.9-fold) and synuclein α (maximal up-regulation 6.5-fold). Our data provide unique insight into SSADHD brain function, confirming astrogliosis and lipid abnormalities previously observed in the null mouse model while highlighting long-term effects on GABAergic/glutamatergic gene expression in this disorder.
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影响因子：
3.3
作者：
Ahrendsen, Jared T.;Anderson, Kevin R.;Anderson, Matthew P.
通讯作者：
Anderson, Matthew P.
影响因子：
3.3
作者：
Police, Anitha;Shankar, Vijay Kumar;Murthy, S. Narasimha
通讯作者：
Murthy, S. Narasimha
影响因子：
1.9
作者：
MURPHY, EJ;STEPHENS, R;HORROCKS, LA
通讯作者：
HORROCKS, LA
影响因子：
30.8
作者：
Hogema, BM;Gupta, M;Gibson, KM
通讯作者：
Gibson, KM
DOI：
10.1007/8904_2015_524
发表时间：
2016-01-01
期刊：
JIMD REPORTS, VOL 30
影响因子：
--
作者：
Schreiber, John M.;Pearl, Phillip L.;Theodore, William H.
通讯作者：
Theodore, William H.