Institute of Neurobiology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, KY, USA.
J Affect Disord. 2021 Nov 1;294:568-573. doi: 10.1016/j.jad.2021.07.064. Epub 2021 Jul 20.
Bipolar disorder (BD) is associated with marked parenchymal brain loss in a significant fraction of patients. The lack of necrosis in postmortem examination suggests an apoptotic process. Emerging evidence suggests that mood stabilizers, like lithium, have antiapoptotic actions. Glutamatergic abnormalities have been associated with BD.
Olfactory neuroepithelial progenitors (ONPs) harvested by biopsy from type I bipolar patients (BD-ONPs, n = 3) and non-bipolar controls (non-BD-ONPs, n = 6), were treated with glutamate at concentrations sufficient to mimic the observed doubling of intracellular sodium known to occur in both mania and bipolar depression, to investigate potential differential lithium effect on both BD-ONPs and non-BD-ONPs.
Apoptosis was detected in BP-ONPs exposed to 0.1 M glutamate for 6 h but in non-BD-ONPs at 24 h. Moreover, after treatment with 0.1 M glutamate treated for 6 h the levels of the pro-apoptotic cleaved-caspase-3 and cleaved-PARP proteins were significantly higher in BD-ONPs compare to non-BD-ONPs. Pretreatment with a therapeutic concentration of 1 mM lithium for 3 days attenuated the glutamate induced apoptosis. Lithium pretreatment 3 days also prevented the DNA fragmentation induced by glutamate, and significantly increased the antiapoptotic phospho-B-Raf and Bcl-2 proteins in BD-ONPs compared to non-BD-ONPs.
ONPs are obtained from subjects with and without bipolar illness, but outcome of their study may still not reflect the biology of the illness.
ONPs derived from BD are more susceptible to glutamate-induced apoptosis. Lithium is associated with a greater increase of anti-apoptotic B-Raf and Bcl-2 expression in BD-ONPs.
躁郁症（BD）与相当一部分患者的显著实质脑损失有关。尸检中没有坏死表明存在凋亡过程。新出现的证据表明，心境稳定剂，如锂，具有抗凋亡作用。谷氨酸能异常与 BD 有关。
通过活检从 I 型双相患者（BD-ONP，n=3）和非双相对照（非-BD-ONP，n=6）中采集嗅神经上皮祖细胞（ONP），用谷氨酸处理浓度足以模拟在躁狂和双相抑郁中观察到的细胞内钠离子倍增，以研究潜在的锂对 BD-ONP 和非-BD-ONP 的差异作用。
暴露于 0.1 M 谷氨酸 6 小时的 BP-ONP 检测到凋亡，但非-BD-ONP 在 24 小时。此外，在用 0.1 M 谷氨酸处理 6 小时后，BD-ONP 中促凋亡的 cleaved-caspase-3 和 cleaved-PARP 蛋白的水平明显高于非-BD-ONP。用治疗浓度 1 mM 锂预处理 3 天可减弱谷氨酸诱导的凋亡。锂预处理 3 天还可防止谷氨酸诱导的 DNA 片段化，并显著增加 BD-ONP 中的抗凋亡磷酸化 B-Raf 和 Bcl-2 蛋白，而非-BD-ONP 则不然。
ONP 是从患有和不患有双相情感障碍的受试者中获得的，但他们的研究结果仍可能无法反映疾病的生物学。
BD 来源的 ONP 对谷氨酸诱导的凋亡更敏感。锂与 BD-ONP 中抗凋亡 B-Raf 和 Bcl-2 表达的增加有关。
