Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: Preliminary studies
| العنوان: | Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: Preliminary studies |
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| المؤلفون: | Melvin G. McInnis, David K. Welsh, Michael McCarthy, Heather Wei, Himanshu K. Mishra, Sara Vandenburgh, William Coryell, Joseph R. Calabrese, Noelle M. Ying, Elliot S. Gershon, Paul D. Shilling, Fred H. Gage, Timothy Nakhla, Angelica Luis, John R. Kelsoe, Wade H. Berrettini, Peter P. Zandi, Martin Alda, John I. Nurnberger, Kristen J. Brennand, Caroline M. Nievergelt, Metta Nguyen, Mark A. Frye, Ketil J. Oedegaard |
| المصدر: | Molecular psychiatry |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, circadian rhythm, medicine.medical_specialty, Bipolar Disorder, Lithium (medication), Period (gene), Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Internal medicine, medicine, Humans, Circadian rhythm, Bipolar disorder, Molecular Biology, Neurons, business.industry, medicine.disease, neuron, PER2, CLOCK, stem cell, Psychiatry and Mental health, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, lithium, Lithium Compounds, Neuron, medicine.symptom, business, Mania, 030217 neurology & neurosurgery, medicine.drug |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1476-5578 1359-4184 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41f30bded33c8ebe757a5de56cac3cdbTest http://europepmc.org/articles/PMC8418615Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....41f30bded33c8ebe757a5de56cac3cdb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765578 13594184 |
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