{"title":"乳酸脱氢酶-1 可能在隐球菌脑膜炎引起的脑能量紊乱中发挥关键作用。","authors":"Qingdong Zhu, Qian Long, Cailing Wei, Jieling Chen, Lanwei Nong, Jianglong Qin, Zhizhong Huang, Yanqing Zheng, Sijun Li","doi":"10.1016/j.jmii.2024.08.009","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cryptococcal meningitis (CM) may affect the conversion of lactate to pyruvate in the brain, resulting in abnormal levels of adenosine triphosphate (ATP) throughout the brain. Lactate conversion to pyruvate is mainly caused by lactic dehydrogenase 1 (LDH1), which is composed of four LDHB subunits. However, the underlying mechanism of LDH1 in CM remains unclear.</p><p><strong>Methods: </strong>Cerebrospinal fluid (CSF) from 17 patients was collected, including eight patients with non-infectious diseases of the central nervous system and nine patients with CM. Based on clinical data and laboratory reports, data regarding intracranial pressure, CSF white cell counts, lactate dehydrogenase (LDH), adenosine deaminase, glucose, protein, and chloridion were collected. Meanwhile, LDH1, LDH5, lactate, pyruvate, and ATP levels were detected in CSF. Whereafter, the levels of lactate, pyruvate, ATP, and the amplitude and frequency of action potentials in the neurons with low expression of LDHB were explored.</p><p><strong>Results: </strong>Intracranial pressure and white cell count in CSF were significantly increased in patients with CM. In patients with CM, the LDH1, pyruvate, and ATP levels in the CSF were significantly decreased, and the levels of lactate were found to be increased. Furthermore, pyruvate and ATP levels were decreased, while lactate was increased in the neurons with low expression of LDHB. The amplitude and frequency of APs in the neurons with low expression of LDHB were significantly decreased.</p><p><strong>Conclusion: </strong>Reduced levels of LDH1 in the brain of patients with CM may lead to increased lactate levels, decreased pyruvate and ATP levels, and negatively affect neuronal activity.</p>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":" ","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lactate dehydrogenase-1 may play a key role in the brain energy disturbance caused by cryptococcal meningitis.\",\"authors\":\"Qingdong Zhu, Qian Long, Cailing Wei, Jieling Chen, Lanwei Nong, Jianglong Qin, Zhizhong Huang, Yanqing Zheng, Sijun Li\",\"doi\":\"10.1016/j.jmii.2024.08.009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cryptococcal meningitis (CM) may affect the conversion of lactate to pyruvate in the brain, resulting in abnormal levels of adenosine triphosphate (ATP) throughout the brain. Lactate conversion to pyruvate is mainly caused by lactic dehydrogenase 1 (LDH1), which is composed of four LDHB subunits. However, the underlying mechanism of LDH1 in CM remains unclear.</p><p><strong>Methods: </strong>Cerebrospinal fluid (CSF) from 17 patients was collected, including eight patients with non-infectious diseases of the central nervous system and nine patients with CM. Based on clinical data and laboratory reports, data regarding intracranial pressure, CSF white cell counts, lactate dehydrogenase (LDH), adenosine deaminase, glucose, protein, and chloridion were collected. Meanwhile, LDH1, LDH5, lactate, pyruvate, and ATP levels were detected in CSF. Whereafter, the levels of lactate, pyruvate, ATP, and the amplitude and frequency of action potentials in the neurons with low expression of LDHB were explored.</p><p><strong>Results: </strong>Intracranial pressure and white cell count in CSF were significantly increased in patients with CM. In patients with CM, the LDH1, pyruvate, and ATP levels in the CSF were significantly decreased, and the levels of lactate were found to be increased. Furthermore, pyruvate and ATP levels were decreased, while lactate was increased in the neurons with low expression of LDHB. The amplitude and frequency of APs in the neurons with low expression of LDHB were significantly decreased.</p><p><strong>Conclusion: </strong>Reduced levels of LDH1 in the brain of patients with CM may lead to increased lactate levels, decreased pyruvate and ATP levels, and negatively affect neuronal activity.</p>\",\"PeriodicalId\":56117,\"journal\":{\"name\":\"Journal of Microbiology Immunology and Infection\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-08-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Microbiology Immunology and Infection\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jmii.2024.08.009\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Microbiology Immunology and Infection","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jmii.2024.08.009","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:隐球菌脑膜炎(CM)可能会影响大脑中乳酸向丙酮酸的转化,导致整个大脑的三磷酸腺苷(ATP)水平异常。乳酸转化为丙酮酸主要是由乳酸脱氢酶 1(LDH1)引起的,LDH1 由四个 LDHB 亚基组成。然而,LDH1 在 CM 中的基本机制仍不清楚:收集了 17 名患者的脑脊液(CSF),其中包括 8 名中枢神经系统非感染性疾病患者和 9 名 CM 患者。根据临床数据和实验室报告,收集了有关颅内压、脑脊液白细胞计数、乳酸脱氢酶(LDH)、腺苷脱氨酶、葡萄糖、蛋白质和氯离子的数据。同时,检测 CSF 中的 LDH1、LDH5、乳酸、丙酮酸和 ATP 水平。随后,研究了 LDHB 低表达神经元的乳酸、丙酮酸、ATP 水平以及动作电位的振幅和频率:结果:CM 患者的颅内压和 CSF 中的白细胞计数明显升高。CM患者脑脊液中的LDH1、丙酮酸和ATP水平明显下降,乳酸水平升高。此外,在 LDHB 低表达的神经元中,丙酮酸和 ATP 水平降低,而乳酸水平升高。LDHB 低表达神经元的 AP 振幅和频率明显降低:结论:CM 患者脑中 LDH1 水平降低可能导致乳酸水平升高、丙酮酸和 ATP 水平降低,并对神经元活动产生负面影响。
Lactate dehydrogenase-1 may play a key role in the brain energy disturbance caused by cryptococcal meningitis.
Background: Cryptococcal meningitis (CM) may affect the conversion of lactate to pyruvate in the brain, resulting in abnormal levels of adenosine triphosphate (ATP) throughout the brain. Lactate conversion to pyruvate is mainly caused by lactic dehydrogenase 1 (LDH1), which is composed of four LDHB subunits. However, the underlying mechanism of LDH1 in CM remains unclear.
Methods: Cerebrospinal fluid (CSF) from 17 patients was collected, including eight patients with non-infectious diseases of the central nervous system and nine patients with CM. Based on clinical data and laboratory reports, data regarding intracranial pressure, CSF white cell counts, lactate dehydrogenase (LDH), adenosine deaminase, glucose, protein, and chloridion were collected. Meanwhile, LDH1, LDH5, lactate, pyruvate, and ATP levels were detected in CSF. Whereafter, the levels of lactate, pyruvate, ATP, and the amplitude and frequency of action potentials in the neurons with low expression of LDHB were explored.
Results: Intracranial pressure and white cell count in CSF were significantly increased in patients with CM. In patients with CM, the LDH1, pyruvate, and ATP levels in the CSF were significantly decreased, and the levels of lactate were found to be increased. Furthermore, pyruvate and ATP levels were decreased, while lactate was increased in the neurons with low expression of LDHB. The amplitude and frequency of APs in the neurons with low expression of LDHB were significantly decreased.
Conclusion: Reduced levels of LDH1 in the brain of patients with CM may lead to increased lactate levels, decreased pyruvate and ATP levels, and negatively affect neuronal activity.
期刊介绍:
Journal of Microbiology Immunology and Infection is an open access journal, committed to disseminating information on the latest trends and advances in microbiology, immunology, infectious diseases and parasitology. Article types considered include perspectives, review articles, original articles, brief reports and correspondence.
With the aim of promoting effective and accurate scientific information, an expert panel of referees constitutes the backbone of the peer-review process in evaluating the quality and content of manuscripts submitted for publication.