Lactate dehydrogenase-1 may play a key role in the brain energy disturbance caused by cryptococcal meningitis

Abstract

Abstract 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.