GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish.

G protein-coupled receptor 139 (GPR139), a highly conserved orphan receptor, is predominantly expressed in the habenula of vertebrate species. Habenula is an ancient epithalamic structure, which is critical to comprehending adaptive behaviors in vertebrates. We have previously demonstrated the role of GPR139 agonists in fear-associated decision-making processes in zebrafish.

Accelerated biological brain aging in major depressive disorder.

Major depressive disorder (MDD) patients commonly encounter multiple types of functional disabilities, such as social, physical, and role functioning. MDD is related to an accreted risk of brain atrophy, aging-associated brain diseases, and mortality. Based on recently available studies, there are correlations between notable biological brain aging and MDD in adulthood.

Nitric oxide mediated kisspeptin regulation of steroidogenesis and gametogenesis in the catfish, Clarias batrachus.

Nitric oxide (NO) is a gaseous molecule that regulates various reproductive functions. It is a well-recognized regulator of GnRH-FSH/LH-sex steroid secretion in vertebrates including fish. Kisspeptin is a recently discovered neuropeptide which also regulates GnRH secretion.

H NMR metabolomics insights into comparative diabesity in male and female zebrafish and the antidiabetic activity of DL-limonene.

Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan injection, and glucose immersion have all been used to induce diabetes and obesity in zebrafish. Currently, studies commonly used both male and female zebrafish, which may influence the outcomes since male and female zebrafish are biologically different.

Teleosts as behaviour test models for social stress.

Stress is an important aspect of our everyday life and exposure to it is an unavoidable occurrence. In humans, this can come in the form of social stress or physical stress from an injury. Studies in animal models have helped researchers to understand the body's adaptive response to stress in human.

Role of Neurokinin B in gametogenesis and steroidogenesis of freshwater catfish, Clarias batrachus.

Neurokinin B (NKB), a recently discovered neuropeptide, plays a crucial role in regulating the kiss-GnRH neurons in vertebrate's brain. NKB is also characterized in gonadal tissues; however, its role in gonads is poorly understood. Therefore, in the present study, the effects of NKB on gonadal steroidogenesis and gametogenesis through in vivo and in vitro approaches using NKB antagonist MRK-08 were evaluated.

Gender Differences in Cortisol and Cortisol Receptors in Depression: A Narrative Review.

Stress is known to have a significant impact on mental health. While gender differences can be found in stress response and mental disorders, there are limited studies on the neuronal mechanisms of gender differences in mental health. Here, we discuss gender and cortisol in depression as presented by recent clinical studies, as well as gender differences in the role of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in stress-associated mental disorders.

Kisspeptin-10 Mitigates α-Synuclein-Mediated Mitochondrial Apoptosis in SH-SY5Y-Derived Neurons via a Kisspeptin Receptor-Independent Manner.

The hypothalamic neurohormone kisspeptin-10 (KP-10) was inherently implicated in cholinergic pathologies when aberrant fluctuations of expression patterns and receptor densities were discerned in neurodegenerative micromilieus. That said, despite variable degrees of functional redundancy, KP-10, which is biologically governed by its cognate G-protein-coupled receptor, GPR54, attenuated the progressive demise of α-synuclein (α-syn)-rich cholinergic-like neurons. Under explicitly modeled environments, in silico algorithms further rationalized the surface complementarities between KP-10 and α-syn when KP-10 was unambiguously accommodated in the C-terminal binding pockets of α-syn.

Integrative Roles of Dopamine Pathway and Calcium Channels Reveal a Link between Schizophrenia and Opioid Use Disorder.

Several theories have been proposed to explain the mechanisms of substance use in schizophrenia. Brain neurons pose a potential to provide novel insights into the association between opioid addiction, withdrawal, and schizophrenia. Thus, we exposed zebrafish larvae at 2 days post-fertilization (dpf) to domperidone (DPM) and morphine, followed by morphine withdrawal.

Social stress-induced serotonin dysfunction activates spexin in male Nile tilapia ().

Social disturbance in interpersonal relationships is the primary source of stress in humans. Spexin (SPX, SPX1a in cichlid), an evolutionarily conserved neuropeptide with diverse physiological functions, is up-regulated in the brain during chronic social defeat stress in teleost. On the other hand, repeated exposure to social stress can lead to dysregulation of the monoaminergic system and increase the vulnerability of developing depression.

Spexin and Galanin in Metabolic Functions and Social Behaviors With a Focus on Non-Mammalian Vertebrates.

Spexin (SPX) and galanin (GAL) are two neuropeptides that are phylogenetically related and have descended from a common ancestral gene. Considerable attention has been given to these two multifunctional neuropeptides because they share GAL receptors 1,2, and 3. Since GAL and SPX-synthesizing neurons have been detected in several brain areas, therefore, it can be speculated that SPX and GAL are involved in various neurophysiological functions.

Kisspeptin-10 Rescues Cholinergic Differentiated SHSY-5Y Cells from α-Synuclein-Induced Toxicity In Vitro.

The neuropathological substrate of dementia with Lewy bodies (DLB) is defined by the inextricable cross-seeding accretion of amyloid-β (Aβ) and α-synuclein (α-syn)-laden deposits in cholinergic neurons. The recent revelation that neuropeptide kisspeptin-10 (KP-10) is able to mitigate Aβ toxicity via an extracellular binding mechanism may provide a new horizon for innovative drug design endeavors. Considering the sequence similarities between α-syn's non-amyloid-β component (NAC) and Aβ's C-terminus, we hypothesized that KP-10 would enhance cholinergic neuronal resistance against α-syn's deleterious consequences through preferential binding.

Role of Habenula in Social and Reproductive Behaviors in Fish: Comparison With Mammals.

Social behaviors such as mating, parenting, fighting, and avoiding are essential functions as a communication tool in social animals, and are critical for the survival of individuals and species. Social behaviors are controlled by a complex circuitry that comprises several key social brain regions, which is called the social behavior network (SBN). The SBN further integrates social information with external and internal factors to select appropriate behavioral responses to social circumstances, called social decision-making.

Metabolomics based biomarker identification of anti-diabetes and anti-obesity properties of Malaysian herbs.

Background: Today, obesity affects over one-third of the global population and is hugely considered the Industrial Revolution's side effect. This multi-factorial disease is continuously spreading across developing countries, including the Middle East and Southeast Asia region, where Malaysia and Darussalam Brunei are the most affected. The sedentary lifestyle and availability of surplus foods have dramatically increased the number of individuals with type 2 diabetes in these countries.

Conserved functions of hypothalamic kisspeptin in vertebrates.

Hypothalamic kisspeptin encoded by KISS1/Kiss1 gene emerged as a regulator of the reproductive axis in mammals following the discovery of the kisspeptin receptor (Kissr) and its role in reproduction. Kisspeptin-Kissr systems have been investigated in various vertebrates, and a conserved sequence of kisspeptin-Kissr has been identified in most vertebrate species except in the avian linage. In addition, multiple paralogs of kisspeptin sequences have been identified in the non-mammalian vertebrates.

MicroRNAs Regulate Cell Cycle and Cell Death Pathways in Glioblastoma.

Glioblastoma (GBM), a grade IV brain tumor, is known for its heterogenicity and its resistance to the current treatment regimen. Over the last few decades, a significant amount of new molecular and genetic findings has been reported regarding factors contributing to GBM's development into a lethal phenotype and its overall poor prognosis. MicroRNA (miRNAs) are small non-coding sequences of RNA that regulate and influence the expression of multiple genes.

Multiple gonadotropin-releasing hormone systems in non-mammalian vertebrates: Ontogeny, anatomy, and physiology.

Three paralogous genes for gonadotropin-releasing hormone (GnRH; gnrh1, gnrh2, and gnrh3) and GnRH receptors exist in non-mammalian vertebrates. However, there are some vertebrate species in which one or two of these paralogous genes have become non-functional during evolution. The developmental migration of GnRH neurons in the brain is evolutionarily conserved in mammals, reptiles, birds, amphibians, and jawed teleost fish.

Intersections in Neuropsychiatric and Metabolic Disorders: Possible Role of TRPA1 Channels.

Neuropsychiatric disorders (NPDs) are a huge burden to the patient, their family, and society. NPDs have been greatly associated with cardio-metabolic comorbidities such as obesity, type-2 diabetes mellitus, dysglycaemia, insulin resistance, dyslipidemia, atherosclerosis, and other cardiovascular disorders. Antipsychotics, which are frontline drugs in the treatment of schizophrenia and off-label use in other NPDs, also add to this burden by causing severe metabolic perturbations.

Habenula orphan G-protein coupled receptors in the pathophysiology of fear and anxiety.

The phasic emotion, fear, and the tonic emotion, anxiety, have been conventionally inspected in clinical frameworks to epitomize memory acquisition, storage, and retrieval. However, inappropriate expression of learned fear in a safe environment and its resistance to suppression is a cardinal feature of various fear-related disorders. A significant body of literature suggests the involvement of extra-amygdala circuitry in fear disorders.

α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox.

Dementia with Lewy bodies (DLB) is epitomized by the pathognomonic manifestation of α-synuclein-laden Lewy bodies within selectively vulnerable neurons in the brain. By virtue of prion-like inheritance, the α-synuclein protein inexorably undergoes extensive conformational metamorphoses and culminate in the form of fibrillar polymorphs, instigating calamitous damage to the brain's neuropsychological networks. This epiphenomenon is nebulous, however, by lingering uncertainty over the quasi "pathogenic" behavior of α-synuclein conformers in DLB pathobiology.

Heterogeneity in GnRH and kisspeptin neurons and their significance in vertebrate reproductive biology.

Vertebrate reproduction is essentially controlled by the hypothalamus-pituitary-gonadal (HPG) axis, which is a central dogma of reproductive biology. Two major hypothalamic neuroendocrine cell groups containing gonadotropin-releasing hormone (GnRH) and kisspeptin are crucial for control of the HPG axis in vertebrates. GnRH and kisspeptin neurons exhibit high levels of heterogeneity including their cellular morphology, biochemistry, neurophysiology and functions.