Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies.
Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies.
复制标题
DOI：
10.1038/s41380-021-01048-7
复制
发表时间：
2021-07
影响因子：
11
通讯作者：
McCarthy MJ
中科院分区：
文献类型：
--
作者：
Mishra HK;Ying NM;Luis A;Wei H;Nguyen M;Nakhla T;Vandenburgh S;Alda M;Berrettini WH;Brennand KJ;Calabrese JR;Coryell WH;Frye MA;Gage FH;Gershon ES;McInnis MG;Nievergelt CM;Nurnberger JI;Shilling PD;Oedegaard KJ;Zandi PP;Pharmacogenomics of Bipolar Disorder Study;Kelsoe JR;Welsh DK;McCarthy MJ
双相情感障碍（BD）是一种神经精神疾病，定义为躁狂/轻躁狂、抑郁和昼夜节律异常的反复发作。锂是治疗BD的有效药物，但30-40%的患者对治疗没有充分反应。先前的工作已经证明，锂影响“时钟基因”的表达，并且锂响应者（Li-R）可以通过昼夜节律的差异与非响应者（Li-NR）区分开来。然而，尚未在来自Li-R和Li-NR的BD患者神经元中评估昼夜节律。我们使用诱导多能干细胞（iPSC）培养神经元前体细胞（NPC）和多巴胺能神经元，这些神经元来自BD患者和匹配的对照组，其特征在于锂反应性。我们在对照组和Li-R组的NPC和神经元中发现了Per 2-luc表达的强昼夜节律，但Li-R组的NPC节律具有较短的昼夜节律周期。Li-NR节律为低振幅和深度减弱。在NPC和神经元中，与对照组相比，两个BD组中PER 2的表达更高。在神经元中，PER 2蛋白水平在BD中高于对照，尤其是在Li-NR样品中。在单个细胞中，与对照组相比，两个BD组中的NPC和神经元节律被去极化。锂延长Li-R和对照神经元的周期，但未能改变Li-NR的节律。与此相反，温度夹带增加幅度在所有组，部分恢复Li-NR神经元的节奏。我们得出结论，神经元昼夜节律异常存在于BD和最明显的Li-NR。BD的节律缺陷可能通过刺激夹带通路而部分可逆。
Bipolar disorder (BD) is a neuropsychiatric illness defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. Lithium is an effective drug for BD, but 30–40% of patients fail to respond adequately to treatment. Previous work has demonstrated that lithium affects the expression of “clock genes” and that lithium responders (Li-R) can be distinguished from non-responders (Li-NR) by differences in circadian rhythms. However, circadian rhythms have not been evaluated in BD patient neurons from Li-R and Li-NR. We used induced pluripotent stem cells (iPSCs) to culture neuronal precursor cells (NPC) and glutamatergic neurons from BD patients characterized for lithium responsiveness and matched controls. We identified strong circadian rhythms in Per2-luc expression in NPCs and neurons from controls and Li-R, but NPC rhythms in Li-R had a shorter circadian period. Li-NR rhythms were low-amplitude and profoundly weakened. In NPCs and neurons, expression of PER2 was higher in both BD groups compared to controls. In neurons, PER2 protein levels were higher in BD than controls, especially in Li-NR samples. In single cells, NPC and neuron rhythms in both BD groups were desynchronized compared to controls. Lithium lengthened period in Li-R and control neurons but failed to alter rhythms in Li-NR. In contrast, temperature entrainment increased amplitude across all groups, and partly restored rhythms in Li-NR neurons. We conclude that neuronal circadian rhythm abnormalities are present in BD and most pronounced in Li-NR. Rhythm deficits in BD may be partly reversible through stimulation of entrainment pathways.
登录
查看更多内容
影响因子：
4.3
作者：
Butti E;Cusimano M;Bacigaluppi M;Martino G
通讯作者：
Martino G
影响因子：
6.8
作者：
Chen HM;DeLong CJ;Bame M;Rajapakse I;Herron TJ;McInnis MG;O'Shea KS
通讯作者：
O'Shea KS
影响因子：
10.6
作者：
Landgraf D;Long JE;Proulx CD;Barandas R;Malinow R;Welsh DK
通讯作者：
Welsh DK
DOI：
10.1016/s0140-6736(16)00143-4
发表时间：
2016-03-12
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hou L;Heilbronner U;Degenhardt F;Adli M;Akiyama K;Akula N;Ardau R;Arias B;Backlund L;Banzato CEM;Benabarre A;Bengesser S;Bhattacharjee AK;Biernacka JM;Birner A;Brichant-Petitjean C;Bui ET;Cervantes P;Chen GB;Chen HC;Chillotti C;Cichon S;Clark SR;Colom F;Cousins DA;Cruceanu C;Czerski PM;Dantas CR;Dayer A;Étain B;Falkai P;Forstner AJ;Frisén L;Fullerton JM;Gard S;Garnham JS;Goes FS;Grof P;Gruber O;Hashimoto R;Hauser J;Herms S;Hoffmann P;Hofmann A;Jamain S;Jiménez E;Kahn JP;Kassem L;Kittel-Schneider S;Kliwicki S;König B;Kusumi I;Lackner N;Laje G;Landén M;Lavebratt C;Leboyer M;Leckband SG;Jaramillo CAL;MacQueen G;Manchia M;Martinsson L;Mattheisen M;McCarthy MJ;McElroy SL;Mitjans M;Mondimore FM;Monteleone P;Nievergelt CM;Nöthen MM;Ösby U;Ozaki N;Perlis RH;Pfennig A;Reich-Erkelenz D;Rouleau GA;Schofield PR;Schubert KO;Schweizer BW;Seemüller F;Severino G;Shekhtman T;Shilling PD;Shimoda K;Simhandl C;Slaney CM;Smoller JW;Squassina A;Stamm T;Stopkova P;Tighe SK;Tortorella A;Turecki G;Volkert J;Witt S;Wright A;Young LT;Zandi PP;Potash JB;DePaulo JR;Bauer M;Reininghaus EZ;Novák T;Aubry JM;Maj M;Baune BT;Mitchell PB;Vieta E;Frye MA;Rybakowski JK;Kuo PH;Kato T;Grigoroiu-Serbanescu M;Reif A;Del Zompo M;Bellivier F;Schalling M;Wray NR;Kelsoe JR;Alda M;Rietschel M;McMahon FJ;Schulze TG
通讯作者：
Schulze TG
影响因子：
7.6
作者：
McCarthy, Michael J.;Wei, Heather;Kelsoe, John R.
通讯作者：
Kelsoe, John R.