Stress induces various neurobiological responses and causes psychiatric disorders, including depression. Monoamine oxidase A (MAO-A) plays an important role in various functions of the brain, such as regulation of mood, anxiety and aggression, and dysregulation of MAO-A is observed in stress-related psychiatric disorders. This study addressed the question whether acute social stress induces changes to transcriptional and/or post-transcriptional regulation of MAO-A expression in the brain. Using male Nile tilapia (Oreochromis niloticus), we investigated whether acute social stress, induced by the presence of a dominant male fish, changes the expression of MAO-A. We measured gene expression of MAO-A by quantitative PCR, enzymatic activity of MAO-A by the luminescent method, and 5-HT and 5-HIAA levels by liquid chromatography-mass spectrometry in the brain of socially stressed and control fish. Socially stressed males showed decreased MAO-A mRNA levels, consistent MAO-A enzymatic activity, increased 5-HT turnover in the brain, and elevated plasma cortisol levels, compared to controls. Our results suggest that acute social stress suppresses the transcription of MAO-A gene, enhances 5-HT metabolism but does not affect the production of MAO-A protein.
Social stress has a high impact on many biological systems in the brain, including serotonergic (5-HT) system-a major drug target in the current treatment for depression. Hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis and monoamine oxidase A (MAO-A) are well-known stress responses, which are involved in the central 5-HT system. Although, many MAO-A inhibitors have been developed and used in the therapeutics of depression, effective management of depression by modulating the activity of MAO-A has not been achieved. Identifying the molecular pathways that regulate the activity of MAO-A in the brain is crucial for developing new drug targets for precise control of MAO-A activity. Over the last few decades, several regulatory pathways of MAO-A consisting of Kruppel like factor 11 (KLF11), Sirtuin1, Ring finger protein in neural stem cells (RINES), and Cell division cycle associated 7-like protein (R1) have been identified, and the influence of social stress on these regulatory factors evaluated. This review explores various aspects of these pathways to expand our understanding of the roles of the HPA axis and MAO-A regulatory pathways during social stress. The first part of this review introduces some components of the HPA axis, explains how stress affects them and how they interact with the 5-HT system in the brain. The second part summarizes the novel regulatory pathways of MAO-A, which have high potential as novel therapeutic targets for depression.
Monoamine oxidase A (MAO-A) is an enzyme that regulates the levels of monoamine neurotransmitters, such as serotonin, noradrenaline and dopamine and it has been used as a therapeutic target for depression. However, MAO-A inhibitors, which directly acts on MAO-A protein, have limited use due to their adverse effects. microRNAs (miRNAs) are 18-22 nucleotide long, small non-coding RNAs, which have recently emerged as regulators of protein levels that could potentially be new therapeutic targets for psychiatric disorders. This review article aims to discuss the current status of the treatment for depression with MAO-A inhibitors and the regulatory factors of MAO-A. Further, the review also proposes possible regulatory mechanisms of MAO-A by miRNAs, which leads to better understanding of the pathology of depressive disorders and their potential use as therapeutic agents.
Stress impairs the hypothalamic-pituitary-gonadal (HPG) axis, probably through its influence on the hypothalamic-pituitary-adrenal (= interrenals in the teleost, HPI) axis leading to reproductive failures. In this study, we investigated the response of hypothalamic neuropeptides, gonadotropin-inhibitory hormone (GnIH), a component of the HPG axis, and corticotropin-releasing hormone (CRH) a component of the HPI axis, to acute social defeat stress in the socially hierarchical male Nile tilapia (Oreochromis niloticus). Localization of GnIH cell bodies, GnIH neuronal processes, and numbers of GnIH cells in the brain during acute social defeat stress was studied using immunohistochemistry. Furthermore, mRNA levels of GnIH and CRH in the brain together with GnIH receptor, gpr147, and adrenocorticotropic hormone (ACTH) in the pituitary were quantified in control and socially defeated fish. Our results show, the number of GnIH-immunoreactive cell bodies and GnIH mRNA levels in the brain and the levels of gpr147 mRNA in the pituitary significantly increased in socially defeated fish. However, CRH and ACTH mRNA levels did not change during social defeat stress. Further, we found glucocorticoid type 2b receptor mRNA in laser captured immunostained GnIH cells. These results show that acute social defeat stress activates GnIH biosynthesis through glucocorticoid receptors type 2b signalling but does not change the CRH and ACTH mRNA expression in the tilapia, which could lead to temporary reproductive dysfunction.
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.