A tale of two transmitters: serotonin and histamine as in vivo biomarkers of chronic stress in mice.
A tale of two transmitters: serotonin and histamine as in vivo biomarkers of chronic stress in mice.
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DOI：
10.1186/s12974-022-02508-9
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发表时间：
2022-06-27
影响因子：
9.3
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中科院分区：
文献类型：
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压力引起的精神疾病（由神经炎症介导）是世界上最紧迫的公共卫生挑战之一。一个可靠的体内压力化学生物标志物将显着改善临床社区的诊断和治疗方法的疾病，如抑郁症。雄性和雌性C57 BL/6 J小鼠经历了慢性应激范例。我们将创新的体内血清素和组胺伏安测量技术、行为测试和尖端的数学方法结合起来，将化学与压力和行为联系起来。炎症诱导的下丘脑组胺的增加与经历慢性应激范式的小鼠体内细胞外海马5-羟色胺的减少共同测量，无论行为表型如何。在具有抑郁症表型的动物中，发现5-羟色胺与抑郁症行为指数的程度之间存在相关性。我们创建了一个高精度的算法，可以预测动物是否暴露在压力下，或者仅仅基于血清素的测量。我们接下来开发了5-羟色胺和组胺调节的模型，该模型预测应激诱导的神经炎症增加组胺能活性，起到抑制5-羟色胺的作用。最后，我们创建了一个压力的数学指数Si，并预测在慢性压力期间，Si很高，同时增加血清素和减少组胺是将血清素恢复到压力前水平的最有效的化学策略。当我们继续追求这个想法时，我们的实验几乎与模型的预测相同。这项工作照亮了慢性应激的两个生物标志物，组胺和血清素，并暗示两者在我们未来对炎症诱导的抑郁症的病理学和治疗的研究中可能很重要。在线版本包含补充材料，可通过10.1186/s12974-022-02508-9获得。
Stress-induced mental illnesses (mediated by neuroinflammation) pose one of the world’s most urgent public health challenges. A reliable in vivo chemical biomarker of stress would significantly improve the clinical communities’ diagnostic and therapeutic approaches to illnesses, such as depression. Male and female C57BL/6J mice underwent a chronic stress paradigm. We paired innovative in vivo serotonin and histamine voltammetric measurement technologies, behavioral testing, and cutting-edge mathematical methods to correlate chemistry to stress and behavior. Inflammation-induced increases in hypothalamic histamine were co-measured with decreased in vivo extracellular hippocampal serotonin in mice that underwent a chronic stress paradigm, regardless of behavioral phenotype. In animals with depression phenotypes, correlations were found between serotonin and the extent of behavioral indices of depression. We created a high accuracy algorithm that could predict whether animals had been exposed to stress or not based solely on the serotonin measurement. We next developed a model of serotonin and histamine modulation, which predicted that stress-induced neuroinflammation increases histaminergic activity, serving to inhibit serotonin. Finally, we created a mathematical index of stress, Si and predicted that during chronic stress, where Si is high, simultaneously increasing serotonin and decreasing histamine is the most effective chemical strategy to restoring serotonin to pre-stress levels. When we pursued this idea pharmacologically, our experiments were nearly identical to the model’s predictions. This work shines the light on two biomarkers of chronic stress, histamine and serotonin, and implies that both may be important in our future investigations of the pathology and treatment of inflammation-induced depression. The online version contains supplementary material available at 10.1186/s12974-022-02508-9.
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DOI：
10.1073/pnas.0800466105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Baganz, Nicole L.;Horton, Rebecca E.;Daws, Lynette C.
通讯作者：
Daws, Lynette C.
影响因子：
6.7
作者：
Brambilla, F;Maggioni, M
通讯作者：
Maggioni, M
影响因子：
2.9
作者：
Forbes, NF;Stewart, CA;Reid, IC
通讯作者：
Reid, IC
影响因子：
3.7
作者：
Fu, Xinxin;Jiao, Jie;Ma, Zhanqiang
通讯作者：
Ma, Zhanqiang
影响因子：
2.4
作者：
Best J;Duncan W;Sadre-Marandi F;Hashemi P;Nijhout HF;Reed M
通讯作者：
Reed M