![]() S1Rs are localized on the membranes of the endoplasmic reticulum at the interface with mitochondria and form a Ca 2+-sensitive and ligand-operated chaperone ( 15). The sigma-1 receptor (S1R) is a nonopioid receptor that is widely expressed in numerous tissues, including the brain and heart. The key mechanism of AF is known as atrial remodeling, as demonstrated in previous studies autonomic dysregulation, neural remodeling, and atrial fibrosis are also involved in the pathogenesis of AF ( 7, 16, 26, 39). Additionally, depression may create an environment that is conducive for the initiation and perpetuation of AF ( 29). Numerous studies have demonstrated that AF and depression often coexist, and patients with AF have been shown to suffer from an increased prevalence of depression ( 37). The results indicate that the S1R could be a potential clinical target for atrial arrhythmia, especially when it is combined with major depressive disorders.Ītrial fibrillation (AF) is a common cardiovascular disease affecting more than 3 million people in the United States alone ( 9, 28). The S1R agonist may target the underlying mechanisms related to AF occurrence. Chronic S1R stimulation alleviates atrial electrical remodeling, fibrosis, and susceptibility to atrial fibrillation (AF). NEW & NOTEWORTHY Chronic stimulation of the sigma-1 receptor (S1R) ameliorates depression-induced autonomic nerve dysfunction by modulating the imbalance between overactivated sympathetic activity and decreased vagal activity. The results indicate that S1R stimulation reduces sympathetic activity and susceptibility to AF by improving depressive behaviors, modulating cardiac autonomic nerve balance, lightening nerve remodeling, and upregulating S1R and ion channel protein expression. Furthermore, rats in the MDS group showed shortened activation latencies, increased effective refractory periods, and lowered frequency of AF incidence duration and fibrosis compared with rats in the MDD group (all P < 0.01). However, rats in the MDS group showed mitigated aforementioned alterations and improved electrical remodeling compared with rats in the MDD group (all P < 0.01). Compared with rats in the CTL group, rats in the MDD group showed significantly augmented sympathetic activity, reduced parasympathetic activity, decreased heart rate variability, and lowered S1R expression in the atrium and hippocampus (all P < 0.01). Depression-like behaviors, such as reduced sucrose preference, decreased body weight gain, and increased immobility time during forced swimming, improved in the MDS group after 4 wk of SA4503 treatment. Male rats were randomly divided into one of the following four treatment groups: saline saline + intragastric administration of SA4503, an agonist of S1R (CTS) chronic unpredictable mild stress (CUMS) to produce depression (MDD) and CUMS + intragastric administration of SA4503 (MDS). ![]() ![]() It is concluded that bipolar cortical GABA interneurons in certain rodent species may develop ChAT immunoreactivity but not VChAT immunoreactivity making the cholinergic relevance of ChAT in the GABA interneurons uncertain and may exclude these neurons from being part of the traditionally defined cholinergic system.The present study aimed to assess the effect of sigma-1 receptor (S1R) stimulation on autonomic nerve dysfunction and susceptibility to atrial fibrillation (AF) in a rat depression model. In the non- Rattus species/strains there was no evidence for localization of ChAT immunoreactivity in any cortical cell bodies using the AB143 and vesicular acetylcholine transporter (VChAT) antibodies despite extensive localization in axons and terminal-like fibres. In all species/strains cortical ChAT immunoreactive axons and terminal-like fibres were localized with the AB144P antibody. The AB144P antibody revealed cortical interneurons in both strains of M. We then examined pigmented (AKR3) and non-pigmented (C3H) strains of Mus musculus, wild caught striped mice ( Rhabdomys pumilio), bushveld gerbil ( Tatera brantsii), greater canerat ( Thryonomys swinderianus) and common molerat ( Cryptomys hottentotus). Initially we verified the presence of ChAT immunoreactive bipolar cell bodies, axons and terminal-like fibres in pigmented (Long-Evans) and non-pigmented (Sprague-Dawley) strains of Rattus norvegicus, confirming that the ChAT polyclonal antibodies (AB144P and AB143, Chemicon VChAT, Sigma) with the immunohistochemical techniques used provided the same staining as previously described for this species. The present study was designed to provide results aimed at testing whether the interneurons with choline acetyltransferase immunoreactivity (ChAT), probably representing GABA interneurons, found in the cerebral cortex of the rat represent a common feature of the order Rodentia.
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