ABSTRACT
OBJECTIVE: Major depressive disorder (MDD) often coexists with hypertension (HYT). DNA methylation has elicited vital functionality in their development. Angiotensin-converting enzyme (ACE) is a vital enzyme in blood pressure. This study investigated the effect of ACE methylation on depression and HYT severity in patients with comorbid MDD and HYT (MDD + HYT). METHODS: A total of 119 patients (41 men, 78 women, average age: 56.8 ± 9.1 years) with MDD + HYT were enrolled, with 89 healthy subjects (29 men, 60 women, average age: 57.4 ± 9.7 years) were enrolled. The Hamilton Depression Rating Scale-17 and self-rating depression scale scoring scales were used to assess the depression degree of patients, serum ACE methylation level in MDD + HYT patients was measured by means of bisulfite sequencing polymerase chain reaction, with subsequent analysis of the diagnostic efficacy of ACE methylation for MDD + HYT. The independent risk factors for sMDD + HYT were explored. RESULTS: Serum ACE methylation levels were significantly increased in MDD + HYT patients. The area under the curve of serum ACE methylation level for accurate diagnosis of MDD + HYT was 0.8471, and the cut-off value was 26.9 (sensitivity 83.19%, specificity 73.03%). ACE methylation was an independent risk factor for sMDD + HYT (P = 0.014; odds ratio, 1.071; 95% confidence interval = 1.014-1.131). CONCLUSION: The elevated serum ACE methylation level (P < 0.001) in patients with MDD + HYT elicited definite diagnostic values for MDD + HYT, and ACE methylation level was independently correlated with sMDD + HYT (P < 0.05).
ABSTRACT
Post-traumatic stress disorder (PTSD) is closely related to the exposure to traumatic events and results in the structural and functional changes of hippocampus. Human basic helix-loop-helix family member e40 (BHLHE40) was reported to be implicated with neuron maturity and neuronal differentiation. The present study aimed to reveal the role of BHLHE40 on single-prolonged stress (SPS) model of PTSD in mice. The morris water maze test, open field test and contextual fear test were conducted to assess memory deficits, anxiety-like behaviors, and freezing of mice. Western blot was performed to identify proteins and reveal their levels in hippocampal tissues. We found that mice receiving SPS exhibited increased anxiety-like behaviors, memory deficits, and prolonged freezing time. The protein levels of BHLHE40 were downregulated in the hippocampal tissues of SPS mice. SPS reduced the protein levels of glutamate receptors, while overexpression of BHLHE40 promoted glutamate receptor protein levels in SPS mice. Moreover, BHLHE40 overexpression activated the PI3K/AKT pathway. BHLHE40 overexpression ameliorated the SPS-induced PTSD-like behavioral deficits. Overall, BHLHE40 promotes glutamate receptor protein levels to ameliorate PTSD-like behaviors with the involvement of the PI3K/AKT pathway. This novel discovery may provide a potential target for the improvement of PTSD.
