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Temporal and spatial characterization of nicotinic acetylcholine receptor expression in Lepeophtheirus salmonis.

Nicotinic acetylcholine receptors (nAChRs) are key mediators of synaptic transmission in invertebrates and major targets of pesticide action. In early life stages of marine Copepoda, such as the parasitic salmon louse (Lepeophtheirus salmonis), the expression dynamics and tissue localization of nAChRs remain poorly characterized. Here, we investigate the expression of nAChR-related transcripts across the life cycle of L. salmonis, and spatial distribution of expression in the early copepodid life stage. Using RNA sequencing of pooled specimens from eleven groups (nauplius I to adults), we iden…

Thyronines and thyronamines: dual modulators of synaptic plasticity, cognitive decline, and geriatric depression in the aging brain.

The aging brain induces cognitive deterioration and geriatric depression via synaptic dysfunction, neuroinflammation, and bioenergetic failure. Recent evidence identifies thyroid hormones (thyronines: T3, T4) and their decarboxylated derivatives (thyronamines, especially 3-iodothyronamine, T1AM) as essential endogenous regulators of these processes. Thyronines influence both genomic and non-genomic pathways in glutamatergic, GABAergic, cholinergic, and monoaminergic signaling, thereby modulating learning and memory. With aging, diminished expression of thyroid hormone transporters (MCT8, OATP1

A new framework for nicotinic receptor-targeted therapeutic strategies in psychiatric and neurodegenerative disorders.

The nicotinic acetylcholine receptors (nAChRs) are key modulators of synaptic transmission and cognitive processing within the central nervous system. These ligand-gated channels, composed of various α and β subunits, mediate a plethora of neuronal functions including attention, memory and executive control. The current perspective article synthesizes recent advances on the contribution of pivotal nAChRs subtypes particularly α4β2, α7, and α5-containing receptors to cortical circuit function, highlighting their relevance in health and disease. In healthy brain, nAChRs regulate excitatory-inhib…

Anatomical and functional organisation of the cholinergic nervous system in the tunicate Botryllus schlosseri.

Acetylcholine (ACh) is an ancient, highly conserved neurotransmitter, yet the functional diversification of cholinergic pathways across earl … le AChE inhibition induces paralysis indicating a critical role for regulated ACh breakdown and non-synaptic transmission. Together, these findings demonstrate that B. schlosseri possesses a sophisticated, dual-effector cholinergic system coordinating both muscular and ciliary networks, providing key insights into the evolutionary diversification of chordate neuromuscu …

EphB1 Receptor Blockade Augments Morphine Antinociception via Inhibiting GRK2-Mediated µ-Opioid Receptor Internalization.

Opioids are the primary treatment for severe pain in clinical practice. However, repeated exposure to opioids leads to tolerance, and underl … and ablation of EphB1 receptors in Vglut2+ neurons enhances opioid-induced inhibition of excitatory synaptic transmission and induction of outward currents in Vglut2+ DH neurons. Mechanistically, EphB1 receptors form a complex with MOR and G protein-coupled receptor kinase 2 (GRK2) and regulate GRK2-mediated phosphorylation of MOR at Ser375, thus controlling MOR intern …

Potassium channel agonists emerging as treatment options for focal epilepsy: are we breaking new ground?

INTRODUCTION: Focal epilepsy is a leading cause of neurological disability, with about one-third of patients failing to achieve seizure freedom despite numerous antiseizure medications (ASMs) are available. Most current therapies broadly modulate synaptic transmission, leading to dose-limiting cognitive, psychiatric, and systemic adverse effects. Kv7 (KCNQ) potassium channels, responsible for the neuronal M-current, represent a high-precision therapeutic target that regulates intrinsic excitability and provides a fundamental 'molecular brake' against pathological firing. AREAS COVERED: This m…

Subacute Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine Exposure Induces Neurobehavioral Deficits and Hippocampal Demyelination in Mice.

Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) is a nitramine explosive widely used in military and industrial fields. While emergin … fferentially expressed proteins in the HMX-exposed hippocampus, which were enriched in myelination, synaptic transmission and neuroactive ligand-receptor interaction pathways. Collectively, our findings demonstrate that subacute HMX exposure induces behavioral deficits and demyelination in mice hippocampus, providing a novel mechanistic insight into HMX neurotoxicity a …

De Novo-Designed Peptide-Engineered Multimodal Platform for Post-Ischemic Stroke Tissue Repair.

Orchestrating tissue regeneration in complex pathologies like post-ischemic stroke requires materials that can precisely regulate multiple signaling pathways. A central challenge is engineering a single platform integrating mechanical, electrical, and biochemical cues to redirect these pathological networks. Here, we present a computation-driven, multimodal hydrogel engineered to function as a programmable regulatory node. The system integrates a computationally screened de novo vasculogenic peptide scaffold and surface-engineered, inflammation-responsive conductive MXene nanosheets. This rati

Semaphorins and Their Role in Neuropathic Pain.

Neuropathic pain is a debilitating condition arising from lesions or diseases affecting the somatosensory nervous system. Despite significant advances in understanding its pathophysiology, the molecular mechanisms underlying the development and persistence of neuropathic pain remain incompletely understood. Semaphorins, a highly conserved family of axon guidance molecules, have emerged as key regulators of neuronal development, synaptic plasticity, immune responses, and neurovascular interactions. Beyond their roles during nervous system development, accumulating evidence indicates that semaph

How molecular mechanisms of aging drive Alzheimer's disease pathology.

Aging is a "multidimensional engine" of biological dysfunction that can fundamentally reshape the pathology of Alzheimer's disease (AD), This review systematically elaborates on how aging synergistically promotes the core pathologies of AD: aging upregulates the activity of β-secretase 1 (BACE1)/γ-secretase, impairs the clearance function of glial cells and meningeal lymphatic drainage, and accelerates Aβ deposition; the imbalance of kinases/phosphatases, dysfunction of molecular chaperones, and aging exosome-mediated propagation of Tau "seeds" facilitate Tau pathology; hyperreactivity of micr

Novel Potential Risk Loci for Migraine in the Portuguese Population.

Common forms of migraine are complex disorders characterized by significant clinical diversity. Their genetic basis has been extensively stu … ical relevance to migraine pathophysiology, reinforcing the importance of neurotransmitter release, synaptic transmission and the involvement of vascular components in migraine pathophysiology.

Engineering Principles of Extracellular Vesicles for Central Nervous System Therapies.

Extracellular Vesicles (EVs) are active mediators of intercellular signaling in the Central Nervous System (CNS), operating alongside synaptic transmission as an extra form of wireless communication between neurons and other brain cell types. Their biocompatibility positions them as promising carriers for neurobiological therapeutics; however, translation hinges on clarifying when and how EVs traverse the Blood-Brain Barrier (BBB) and how their design can be aligned to pathophysiology. We synthesize evidence for BBB transport from in vitro models and in vivo visualization and functional studie…

The role of impaired mitochondrial function in neurological manifestations of mitochondrial diseases.

Mitochondria are essential organelles responsible for cellular energy production and the regulation of key metabolic and signalling pathways. Their function depends on the coordinated expression of both mitochondrial and nuclear genomes, and mitochondrial dysfunction leads to a diverse group of mitochondrial diseases. The nervous system is particularly vulnerable to mitochondrial dysfunction due to the high energetic demands and complex morphology of neurons. Neurons rely heavily on mitochondrial ATP production to support processes such as synaptic transmission, axonal transport, and calcium h…

Мозговые липидные метаболизмы и перенос: последствия для нейродегенерации и терапевтических стратегий: всеобъемлющий обзор.

В этом всеобъемлющем обзоре 2024 года рассматриваются ключевые функции липидов в неврологическом здоровье, а также подчеркивается их жизненно важный вклад в структуру, функцию и патологию мозга. Сложный липидный состав мозга, состоящий из фосфолипидов, шпинголипидов, холестерина, гликолипидов и полиненасыщенных жирных кислот, поддерживает целостность мембран, синаптическую трансмиссию и миелинацию. Производство липидов, метаболизм и перенос в центральной нервной системе тщательно контролируются, что требует специализированного взаимодействия между нейронами, глиарными клетками и мозговым барье

Совпадение в аннотации оригинала
This 2024comprehensive review examines the crucial functions of lipids in neurological health, highlighting their vital contributions to bra … ingolipids, cholesterol, glycolipids, and polyunsaturated fatty acids, supports membrane integrity, synaptic transmission, and myelination. Lipid production, metabolism, and transport in the central nervous system are meticulously controlled, necessitating specialised interactions among neurones, glial cells, and the blood-brain barrier. Lipid homeostasis dysregulation …

Characterization of postsynaptic glutamate transporter functionality in the zebrafish retinal first synapse across different wavelengths.

In the zebrafish retina, incident light undergoes wavelength-dependent processing encompassing mechanisms such as color opponency, contrast enhancement, and motion detection prior to neural transmission to the brain proper. In darkness, photoreceptors continuously release glutamate into the synaptic cleft, a process that diminishes in response to increased light intensity, thereby conveying visual signals to ON and OFF bipolar cells. Specifically, in zebrafish, the ON pathway signal transduction is mediated by metabotropic glutamate receptor 6b (mGluR6b) and Excitatory Amino Acid Transporters

Chemogenetic Modulation of Astrocytic Activity Rescues Hippocampus Associated Neurodegeneration in Alzheimer's Disease Mice Model 5xFAD.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by Aβ-amyloid accumulation and cognitive decline. Despite extensive research, effective treatments remain elusive. Astrocytes, the most abundant glial cells, play a crucial role in synaptic transmission, neuronal excitability, and plasticity. In AD, astrocytes become reactive, exhibiting aberrant calcium signaling and altered neurotransmitter release, making them promising targets for disease-modifying therapies. To address this, we explored designer receptors exclusively activated by designer drugs (DREADDs), spe…

Neuroimaging changes in pre-treatment and post-treatment patients with bipolar disorder and their relationship with genetic characteristics.

OBJECTIVE: Bipolar disorder (BD) patients may exhibit common and significant changes in brain activity before and after treatment. We aim to … ed genes associated with changes in FC in BD, which were enriched in biological processes including synaptic transmission and ion transport. CONCLUSIONS: In summary, changes in FC of the SN may be potential neuroimaging markers of treatment effectiveness in patients with BD. Our genetic neuroimaging association analysis may help to comprehensively understand the molec …

Targeted drug screening for autism based on Cav1.2 calcium ion channel.

This study presents a targeted virtual drug screening approach for autism spectrum disorder (ASD), focusing on Cav1.2 calcium ion channels as potential therapeutic targets. ASD is a complex neurodevelopmental disorder characterized by impairments in social communication and behavior, with genetic factors playing a significant role. Cav1.2 channels have been implicated in the pathophysiology of ASD due to their role in regulating neuronal excitability and synaptic transmission. We employed computational methods to virtually screen a large database of compounds for their potential to modulate Ca…

Infantile Cerebellar-Retinal Degeneration Associated With Novel ACO2 Variants: Clinical Features and Insights From a Drosophila Model.

Infantile Cerebellar-Retinal Degeneration (ICRD) is an autosomal recessive neuro-disability associated with hypotonia, seizures, optic atrop … disrupting sleep and circadian rhythms. Mis-expression of mAcon1 in the eye led to impaired visual synaptic transmission and neurodegeneration. These experiments mirrored certain aspects of the human disease, providing a foundation for understanding its biological processes and pathogenic mechanisms, and offering insights into potential targets to screen for future tr …

The Involvement of the Endocannabinoid, Glutamatergic, and GABAergic Systems in PTSD.

Post-traumatic stress disorder (PTSD) is a debilitating mental health condition that develops in response to traumatic events. The endocannabinoid, glutamatergic, and GABAergic systems play crucial roles in the neurobiological mechanisms of PTSD. Both the endocannabinoid, glutamatergic, and GABAergic systems are involved in synaptic remodeling and neuronal differentiation, ensuring efficient information transmission in the brain. Their interplay influences motivation, behavior, sensory perception, pain regulation, and visual processing. Additionally, these systems regulate processes such as ce