Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

The brain's Renin-Angiotensin System plays an important role in the modulation of mental state. Previously we demonstrated that activated angiotensin (Ang) converting enzyme (ACE) 2, which converts Ang II into Ang (1-7), or the intracerebroventricular administration of Ang (1-7) produced an antidepressant-like effect in mice via Mas receptors (MasR). Since the ACE inhibitor Captopril (Cap) increases Ang (1-7) in the brain, it remains unknown whether Cap affects the depressive-like behavior of olfactory bulbectomized (OBX) mice, an animal model of depression. We tested the effect of Cap on the depressive-like behavior of these mice in the tail-suspension test, quantified ACE2, p-AMP activated protein kinase (AMPK), and brain-derived neurotrophic factor (BDNF) using western blots, and examined the changes in Ang (1-7) level, neurogenesis, and in the expression of ACE2 and MasR on various cell types in the hippocampus using immunohistochemistry. While OBX mice exhibited a depressive-like behavior in the tail-suspension test, as well as a reduction in ACE2, Ang (1-7), p-AMPK, BDNF, and hippocampal neurogenesis, these changes were prevented by Cap administration. The intracerebroventricular administration of Ang (1-7) improved the OBX-induced depressive-like behavior. Except for the changes in ACE2 and Ang (1-7), the effects of Cap were inhibited by the coadministration of A779 (MasR inhibitor) or Compound-C (AMPK inhibitor). ACE2 localized to all cell types, while MasR localized to microglia and neurons. Our results suggest that Cap may act on ACE2-positive cells in the hippocampus to increase ACE2 expression level, thereby enhancing signaling in the ACE2/Ang (1-7)/MasR/AMPK/BDNF pathway and producing antidepressant-like effects.

Background: Cognitive impairment is a common clinical symptom of patients with major depressive disorder (MDD). Transcranial magnetic stimulation-evoked potentials (TEPs) detect cortical excitability and connectivity and provide potential biomarkers for MDD patients and their cognitive impairment. This study aimed to investigate the interrelationships between clinical symptoms, cognitive function, and electrophysiological marker TEPs in patients with MDD.

Methods: A total of 117 participants were recruited, including 59 MDD patients and 58 healthy controls. Clinical symptoms were assessed by the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, and cognitive functioning was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). TEPs were recorded by transcranial magnetic stimulation combined with electroencephalography (TMS-EEG).

Results: MDD patients exhibited lower RBANS total (P < 0.001), immediate memory (P = 0.001), language (P = 0.003), attention (P < 0.001), and delayed memory (P = 0.008) scores than HCs. Patients with MDD had larger amplitudes for N100 (P = 0.040) and N280 (P = 0.037), compared to HCs. Correlation analysis indicated significant correlations between the following RBANS scores and TEPs: language and N45 amplitude (r = 0.222, P = 0.024), language and P60 amplitude (r = 0.278, P = 0.004), attention and P180 amplitude (r = 0.213, P = 0.030), RBANS total score and P30 amplitude (r = 0.198, P = 0.044), visuospatial/constructional index and N100 amplitude (r = -0.272, P = 0.005).

Conclusion: The results of this study indicate that cortical dysfunction and cognitive impairment are present in patients with MDD and that there is a strong correlation between them, suggesting that TEPs detected by the TMS-EEG may be used as a biomarker for MDD patients and their cognitive impairment.