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Objective
Accumulating evidences indicate that gastrin-releasing peptide receptor (GRPR) may contribute to the pathophysiology of depression. However, the mechanism of the involvement of GRPR in the progression of depression remains unclear. Here, we showed the extent to which stress and antidepressant treatment impact GRPR expression, and explored...
Citations
... However, no significant differences in tracer uptake between control and RSD defeated animals were observed in any brain region [35], which may be ascribed to the short duration of the RSD protocol. In contrast, increased 5HT 2A receptor availability (BP ND ) has been reported in animals exposed to the CUMS paradigm [81], which is in agreement with the analysis of post-mortem samples of patients with history of MDD [82]. The 5HT 2A receptor density in hippocampus, amygdala, prefrontal cortex, striatum and olfactory structures [83] in both humans and animals has been associated with the response to therapy with selective serotonin reuptake inhibitors [84]. ...
Major depressive disorder is a growing and poorly understood pathology. Due to technical and ethical limitations, a significant proportion of the research on depressive disorders cannot be performed on patients, but needs to be investigated in animal paradigms. Over the years, animal studies have provided new insight in the mechanisms underlying depression. Several of these studies have used PET imaging for the non-invasive and longitudinal investigation of the brain physiology. This review summarises the findings of preclinical PET imaging in different experimental paradigms of depression and compares these findings with observations from human studies. Preclinical PET studies in animal models of depression can be divided into three main different approaches: (a) investigation of glucose metabolism as a biomarker for regional and network involvement, (b) evaluation of the availability of different neuroreceptor populations associated with depressive phenotypes, and (c) monitoring of the inflammatory response in phenotypes of depression. This review also assesses the relevance of the use of PET imaging techniques in animal paradigms for the understanding of specific aspects of the depressive-like phenotypes, in particular whether it might contribute to achieve a more detailed characterisation of the clinical depressive phenotypes for the development of new therapies for depression.
... Secondly, GPR158 expression could also be induced by androgens, but GPR158 promotes PCa cell proliferation independent of AR functionality, which requires its entry into the nucleus [16] (Figure 5c). The interruption of GPR158 expression could nonetheless influence the level of androgens, probably 5-HT, oxytocin, and ACTH in the plasma and BDNF in the brain, which contributes to the etiology of affective disorders and tumors [16,74,99,100]. ...
G-protein-coupled receptors (GPCRs) remain one of the most successful targets for therapeutic drugs approved by the US Food and Drug Administration (FDA). Many novel orphan GPCRs have been identified by human genome sequencing and considered as putative targets for refractory diseases. Of note, a series of studies have been carried out involving GPCR 158 (or GPR158) since its identification in 2005, predominantly focusing on the characterization of its roles in the progression of cancer and mental illness. However, advances towards an in-depth understanding of the biological mechanism(s) involved for clinical application of GPR158 are lacking. In this paper, we clarify the origin of the GPR158 evolution in different species and summarize the relationship between GPR158 and different diseases towards potential drug target identification, through an analysis of the sequences and substructures of GPR158. Further, we discuss how recent studies set about unraveling the fundamental features and principles, followed by future perspectives and thoughts, which may lead to prospective therapies involving GPR158.
... As previously described (12), the mice were allowed to adapt to 1% sucrose solution before the test. For the test, the animals were presented with 2 bottles for 24 hours after 24 hours of water and food deprivation, 1 containing distilled water and the other containing 1% sucrose solution. ...
... One day later, the animals were forced to swim for 6 minutes once more, and their immobility time in the last 4 minutes was rescored. The following actions were recognized as immobility: no struggling; upright floating posture; and occasional limb movement with the head above the water but without body movement (12). ...
Background:
Depression is a major public health challenge that imposes a great societal burden. Depression has been attributed to the decreased level of neurotransmitters and brain-derived neurotrophic factor (BDNF) levels. Chinese herbal medicine Jie Yu Chu Fan (JYCF) capsule has been shown to be effective in the management of depression. However, the mechanism has yet to be determined. This study aimed to explore the activity of JYCF against depression by establishing a mouse model of chronic unpredictable mild stress (CUMS) with fluoxetine as the positive control drug.
Methods:
The open field test, sucrose preference test, forced swim test, and tail suspension test were carried out to observe the behavioral changes of animals. The levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine, as well as their respective metabolic products 5-hydroxyindoleacetic acid, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid in the mouse hippocampi were quantified by high-performance liquid chromatography (HPLC). Cell proliferation and apoptosis, and early and mature nerve cells in the hippocampi were observed by immunofluorescence. Reverse transcription polymerase chain reaction was used to identify BDNF expression in the hippocampi.
Results:
After 5 weeks of unpredictable stimulation, a CUMS mouse model was successfully obtained, as indicated by sharply decreased sucrose preference and locomotor activity, as well as an increased immobility time in the forced swim test. Our results demonstrated that treatment with JYCF (1 and 5 g/kg) and fluoxetine (20 mg/kg) dramatically reversed the behavioral abnormalities in CUMS mice. At 1 g/kg, JYCF significantly increased NE, DA, and HVA levels in the hippocampi of CUMS mice. JYCF up-regulated the mRNA expression of BDNF and promoted cell proliferation in hippocampi of CUMS mice.
Conclusions:
Our study demonstrated that JYCF exhibits antidepressant activity comparable to that of fluoxetine in CUMS mice. Moreover, the antidepressant-like activity of JYCF was shown to be mediated by enhancing hippocampal nerve cell neurogenesis through increasing the levels of monoamine neurotransmitters and BDNF expression.
The monoaminergic dysfunction plays a central role in major depressive disorder (MDD), a mental disturbance associated with constant feeling of sadness and lack of interest. The available treatments do not present a desirable efficacy and some of them provoke several adverse effects. In this context, organoselenium compounds and molecules containing the indolizine nucleus have demonstrated interesting pharmacological properties, including antidepressant-like effects. In this study, the antidepressant-like effect of 2-phenyl-1-(phenylselanyl)indolizine (SeI), a selenium-containing indolizine derivative, was investigated on the forced swimming test (FST) and on the tail suspension test (TST) in male Swiss mice. The involvement of the serotonergic system in this effect was also accessed. The selenium compound SeI (10-100 mg/kg, intragastrical (i.g.)) was administered 0.5 h before the behavioral tests, and it diminished the immobility on both FST and TST experiments, which is an indication of antidepressant-like effect. No changing in the locomotor motion was observed in the open-field test (OFT). The anti-immobility effect of SeI was not altered by the preadministration of the selective serotonergic receptor antagonists ondansetron (1 mg/kg, intraperitoneally (i.p.), antagonist of 5-HT3 receptor) and WAY100635 (0.1 mg/kg, subcutaneous route (s.c.), antagonist of 5-HT1A receptor). In contrast, the preadministration of ketanserin (1 mg/kg, i.p., antagonist of 5-HT2A/C receptor) blocked this effect, demonstrating that the antidepressant-like effect of SeI involves 5-HT2A/C. In addition, molecular docking studies showed a strong interaction between SeI and the receptors of 5-HT2A and 5-HT2C. The toxicological results demonstrated that SeI has low potential to cause adverse effects in mice. It was found that the antidepressant-like effect of SeI is related to modulation of the serotonergic system, and this selenium compound could be included in new treatment approaches for MDD.
Introdução: O Transtorno Depressivo Maior é uma condição médica comum na população, que pode atingir não somente a capacidade mental, mas também a capacidade física, causando inclusive incapacidade laboral. A sua causa ainda permanece desconhecida, apesar de algumas teorias terem ganhado espaço, como as hipóteses da neurogênese e da neuroplasticidade, que surgiram num contexto onde a clássica hipótese das monoaminas já não explica todos os casos. Nesse contexto, uma forte associação entre a hiperatividade do eixo hipotálamo-pituitária-adrenal, bem como dos hormônios do trato gastrointestinal, foram destacados em estudos, levantando a hipótese de a depressão ter fatores metabólicos associados, levando inclusive a caracterização de doença metabólica segundo alguns autores. Objetivos: Desta forma, o presente estudo busca analisar o feito comportamental do hormônio do trato gastrointestinal GRP tendo em vista as evidências presentes sobre a possível relação deste com a fisiopatologia da depressão. Método: Foram selecionados 20 camundongos Swiss para realização do procedimento da derrota social, análise com teste do nado forçado e intervenção com Fluoxetina no controle e GRP no experimental. Resultados: O estresse de derrota social aumentou o tempo de imobilidade no teste do nado forçado em 13 segundos nos camundongos submissos, a injeção de GRP reduziu o tempo de imobilidade com uma diferença de 78 segundos para o grupo controle tratado com Fluoxetina. Conclusão: Assim, o GRP, comparado aos outros hormônios estudados na depressão apresentou efeito positivo no quadro depressivo e possível terapia para seu tratamento.
