Therapeutic of Candesartan and Music Therapy in Diabetic Retinopathy with Depression in Rats

Abstract

This study aimed to investigate the therapeutic effects of candesartan combined with music therapy on diabetic retinopathy with depression and to assess the molecular mechanisms. Associated animal model of diabetes mellitus and depression was established in rats. Pathological changes in the hippocampus were detected by haematoxylin eosin (H&E) staining. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was used to detect retinal cell apoptosis. Angiotensin II (Ang II) in peripheral blood and neurotransmitters, including serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in the hippocampus, was measured by enzyme linked immunosorbent assay (ELISA). Fluorescence quantitative PCR and western blotting were used to detect the expression of brain-derived neurotrophic factor (BDNF) and c-fos in the hippocampus. Our data showed that chromatin aggregation and cytoplasmic vacuolation were observable in the hippocampal cells of the rats in the model group, while candesartan and music therapy could reduce morphological changes in the hippocampus of diabetic rats with depression. Compared with the control group, the apoptosis of retinal cells was significantly higher, the contents of 5-HT, DA, and NE in the hippocampus were significantly lower, Ang II level in peripheral blood was significantly higher, and the expression of BDNF and c-fos in the hippocampus decreased significantly in the model group. By contrast, candesartan or candesartan + music therapy ameliorated the changes in retina cell apoptosis, reduction of neurotransmitters, increase in AII, and the expression of c-fos and BDNF. Especially, music therapy further improved the effects of candesartan on retina cell apoptosis and neurotransmitter release in diabetic retinopathy rats with depression. In conclusion, candesartan and music therapy have an additive effect in DM with both visual impairment and depression, which might serve a potential alternative treatment for this complex disease.

Role of brain renin–angiotensin system in depression: A new perspective

“…Similarly, the AT1 receptor blocker telmisartan reduces depression in diabetic rats. Besides, ACEIs such as candesartan produce an antidepressant effect in animal model study 120 . The underlying mechanisms for the antidepressant effects of ARBs and ACEIs might be related to the upregulation of ACE2/Ang1‐7/MASR.…”

“…Besides, ACEIs such as candesartan produce an antidepressant effect in animal model study. 120 The underlying mechanisms for the antidepressant effects of ARBs and ACEIs might be related to the upregulation of ACE2/Ang1‐7/MASR. Different experimental studies have observed that overexpression of ACE2 and Ang1‐7 in transgenic rats promotes antidepressant and antianxiety effects that are reversed by using MASR antagonists.…”

Imidazoles as Serotonin Receptor Modulators for Treatment of Depression: Structural Insights and Structure–Activity Relationship Studies

“…It has completed phase II trials (NCT00809562, NCT01437657) and is under further investigation by Hoffmann-La Roche for treatment-resistant and major depressive disorders. Candesartan is an angiotensin receptor blocker mainly used for hypertension treatment but has also been found to reverse depression-like symptoms in preclinical studies in the initial phase [ 140 , 141 ]. But, in clinical trials, it was withdrawn from phase I in the early phase (NCT04430959), and phase IV studies were terminated due to the adverse effects in treated patients (NCT01794455).…”

Classical music restored fertility status in rat model of premature ovarian failure

“…[22,23]. Classical music therapy has been practiced successfully on mice animal models for stress [24][25][26], diabetes mellitus [27], breast cancer [28], bone cancer [29], Alzheimer's disease [20], autism [30], and schizophrenia [31].…”