The brain-bone axis: unraveling the complex interplay between the central nervous system and skeletal metabolism.

The brain-bone axis has emerged as a captivating field of research, unveiling the intricate bidirectional communication between the central nervous system (CNS) and skeletal metabolism. This comprehensive review delves into the current state of knowledge surrounding the brain-bone axis, exploring the complex mechanisms, key players, and potential clinical implications of this fascinating area of study. The review discusses the neural regulation of bone metabolism, highlighting the roles of the sympathetic nervous system, hypothalamic neuropeptides, and neurotransmitters in modulating bone remodeling. In addition, it examines the influence of bone-derived factors, such as osteocalcin and fibroblast growth factor 23, on brain function and behavior. The therapeutic potential of targeting the brain-bone axis in the context of skeletal and neurological disorders is also explored. By unraveling the complex interplay between the CNS and skeletal metabolism, this review aims to provide a comprehensive resource for researchers, clinicians, and students interested in the brain-bone axis and its implications for human health and disease.

Division of labor for defensive retaliation and preemption by the peripheral and central nervous systems in the nudibranch Berghia.

Relatively little is known about how peripheral nervous systems (PNSs) contribute to the patterning of behavior in which their role transcends the simple execution of central motor commands or mediation of reflexes. We sought to draw inferences to this end in the aeolid nudibranch Berghia stephanieae, which generates a rapid, dramatic defense behavior, "bristling." This behavior involves the coordinated movement of cerata, dozens of venomous appendages emerging from the animal's mantle. Our investigations revealed that bristling constitutes a stereotyped but non-reflexive two-stage behavior: an initial adduction of proximate cerata to sting the offending stimulus (stage 1) followed by a coordinated radial extension of remaining cerata to create a pincushion-like defensive screen around the animal (stage 2). In decerebrated specimens, stage 1 bristling was preserved, while stage 2 bristling was replaced by slower, uncoordinated ceratal movements. We conclude from these observations that, first, the animal's PNS and central nervous system (CNS) mediate stages 1 and 2 of bristling, respectively; second, the behavior propagates through the body utilizing both peripheral- and central-origin nerve networks that support different signaling kinetics; and third, the former network inhibits the latter in the body region being stimulated. These findings extend our understanding of the PNS' computational capacity and provide insight into a neuroethological scheme in which the CNS and PNS both independently and interactively pattern different aspects of non-reflexive behavior.

Perineuronal Nets in the CNS: Architects of Memory and Potential Therapeutic Target in Neuropsychiatric Disorders.

The extracellular matrix (ECM) within the brain possesses a distinctive composition and functionality, influencing a spectrum of physiological and pathological states. Among its constituents, perineuronal nets (PNNs) are unique ECM structures that wrap around the cell body of many neurons and extend along their dendrites within the central nervous system (CNS). PNNs are pivotal regulators of plasticity in CNS, both during development and adulthood stages. Characterized by their condensed glycosaminoglycan-rich structures and heterogeneous molecular composition, PNNs not only offer neuroprotection but also participate in signal transduction, orchestrating neuronal activity and plasticity. Interfering with the PNNs in adult animals induces the reactivation of critical period plasticity, permitting modifications in neuronal connections and promoting the recovery of neuroplasticity following spinal cord damage. Interestingly, in the adult brain, PNN expression is dynamic, potentially modulating plasticity-associated states. Given their multifaceted roles, PNNs have emerged as regulators in the domains of learning, memory, addiction behaviors, and other neuropsychiatric disorders. In this review, we aimed to address how PNNs contribute to the memory processes in physiological and pathological conditions.

Regulators of Oligodendrocyte Differentiation.

Myelination has evolved as a mechanism to ensure fast and efficient propagation of nerve impulses along axons. Within the central nervous system (CNS), myelination is carried out by highly specialized glial cells, oligodendrocytes. The formation of myelin is a prolonged aspect of CNS development that occurs well into adulthood in humans, continuing throughout life in response to injury or as a component of neuroplasticity. The timing of myelination is tightly tied to the generation of oligodendrocytes through the differentiation of their committed progenitors, oligodendrocyte precursor cells (OPCs), which reside throughout the developing and adult CNS. In this article, we summarize our current understanding of some of the signals and pathways that regulate the differentiation of OPCs, and thus the myelination of CNS axons.

Extracellular Vesicles in the Central Nervous System: A Novel Mechanism of Neuronal Cell Communication.

Cell-to-cell communication is essential for the appropriate development and maintenance of homeostatic conditions in the central nervous system. Extracellular vesicles have recently come to the forefront of neuroscience as novel vehicles for the transfer of complex signals between neuronal cells. Extracellular vesicles are membrane-bound carriers packed with proteins, metabolites, and nucleic acids (including DNA, mRNA, and microRNAs) that contain the elements present in the cell they originate from. Since their discovery, extracellular vesicles have been studied extensively and have opened up new understanding of cell-cell communication; they may cross the blood-brain barrier in a bidirectional way from the bloodstream to the brain parenchyma and vice versa, and play a key role in brain-periphery communication in physiology as well as pathology. Neurons and glial cells in the central nervous system release extracellular vesicles to the interstitial fluid of the brain and spinal cord parenchyma. Extracellular vesicles contain proteins, nucleic acids, lipids, carbohydrates, and primary and secondary metabolites. that can be taken up by and modulate the behaviour of neighbouring recipient cells. The functions of extracellular vesicles have been extensively studied in the context of neurodegenerative diseases. The purpose of this review is to analyse the role extracellular vesicles extracellular vesicles in central nervous system cell communication, with particular emphasis on the contribution of extracellular vesicles from different central nervous system cell types in maintaining or altering central nervous system homeostasis.

Microglia regulation of central nervous system myelin health and regeneration.

Microglia are resident macrophages of the central nervous system that have key functions in its development, homeostasis and response to damage and infection. Although microglia have been increasingly implicated in contributing to the pathology that underpins neurological dysfunction and disease, they also have crucial roles in neurological homeostasis and regeneration. This includes regulation of the maintenance and regeneration of myelin, the membrane that surrounds neuronal axons, which is required for axonal health and function. Myelin is damaged with normal ageing and in several neurodegenerative diseases, such as multiple sclerosis and Alzheimer disease. Given the lack of approved therapies targeting myelin maintenance or regeneration, it is imperative to understand the mechanisms by which microglia support and restore myelin health to identify potential therapeutic approaches. However, the mechanisms by which microglia regulate myelin loss or integrity are still being uncovered. In this Review, we discuss recent work that reveals the changes in white matter with ageing and neurodegenerative disease, how this relates to microglia dynamics during myelin damage and regeneration, and factors that influence the regenerative functions of microglia.

Deciphering Oligodendrocyte Lineages in the Human Fetal Central Nervous System Using Single-Cell RNA Sequencing.

Oligodendrocytes form myelin sheaths and wrap axons of neurons to facilitate various crucial neurological functions. Oligodendrocyte progenitor cells (OPCs) persist in the embryonic, postnatal, and adult central nervous system (CNS). OPCs and mature oligodendrocytes are involved in a variety of biological processes such as memory, learning, and diseases. How oligodendrocytes are specified in different regions in the CNS, in particular in humans, remains obscure. We here explored oligodendrocyte development in three CNS regions, subpallium, brainstem, and spinal cord, in human fetuses from gestational week 8 (GW8) to GW12 using single-cell RNA sequencing. We detected multiple lineages of OPCs and illustrated distinct developmental trajectories of oligodendrocyte differentiation in three CNS regions. We also identified major genes, particularly transcription factors, which maintain status of OPC proliferation and promote generation of mature oligodendrocytes. Moreover, we discovered new marker genes that might be crucial for oligodendrocyte specification in humans, and detected common and distinct genes expressed in oligodendrocyte lineages in three CNS regions. Our study has demonstrated molecular heterogeneity of oligodendrocyte lineages in different CNS regions and provided references for further investigation of roles of important genes in oligodendrocyte development in humans.

Interactions between neural cells and blood vessels in central nervous system development.

The sophisticated function of the central nervous system (CNS) is largely supported by proper interactions between neural cells and blood vessels. Accumulating evidence has demonstrated that neurons and glial cells support the formation of blood vessels, which in turn, act as migratory scaffolds for these cell types. Neural progenitors are also involved in the regulation of blood vessel formation. This mutual interaction between neural cells and blood vessels is elegantly controlled by several chemokines, growth factors, extracellular matrix, and adhesion molecules such as integrins. Recent research has revealed that newly migrating cell types along blood vessels repel other preexisting migrating cell types, causing them to detach from the blood vessels. In this review, we discuss vascular formation and cell migration, particularly during development. Moreover, we discuss how the crosstalk between blood vessels and neurons and glial cells could be related to neurodevelopmental disorders.

The Gut-Liver-Brain Axis: From the Head to the Feet.

The gut-liver-brain axis, a multifaceted network of communication, intricately connects the enteric, hepatic, and central nervous systems [...].

Environmental concentrations of tire rubber-derived 6PPD-quinone alter CNS function in zebrafish larvae.

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone) is a degradation product of 6PPD, an antioxidant widely used in rubber tires. 6PPD-quinone enters aquatic ecosystems through urban stormwater runoff and has been identified as the chemical behind the urban runoff mortality syndrome in coho salmon. However, the available data suggest that the acute effects of 6PPD-quinone are restricted to a few salmonid species and that the environmental levels of this chemical should be safe for most fish. In this study, larvae of a "tolerant" fish species, Danio rerio, were exposed to three environmental concentrations of 6PPD-quinone for only 24 h, and the effects on exploratory behavior, escape response, nonassociative learning (habituation), neurotransmitter profile, wake/sleep cycle, circadian rhythm, heart rate and oxygen consumption rate were analyzed. Exposure to the two lowest concentrations of 6PPD-quinone resulted in altered exploratory behavior and habituation, an effect consistent with some of the observed changes in the neurotransmitter profile, including increased levels of acetylcholine, norepinephrine, epinephrine and serotonin. Moreover, exposure to the highest concentration tested altered the wake/sleep cycle and the expression of per1a, per3 and cry3a, circadian clock genes involved in the negative feedback loop. Finally, a positive chronotropic effect of 6PPD-quinone was observed in the hearts of the exposed fish. The results of this study emphasize the need for further studies analyzing the effects of 6PPD-quinone in "tolerant" fish species.

Wake-like skin patterning and neural activity during octopus sleep.

While sleeping, many vertebrate groups alternate between at least two sleep stages: rapid eye movement and slow wave sleep1-4, in part characterized by wake-like and synchronous brain activity, respectively. Here we delineate neural and behavioural correlates of two stages of sleep in octopuses, marine invertebrates that evolutionarily diverged from vertebrates roughly 550 million years ago (ref. 5) and have independently evolved large brains and behavioural sophistication. 'Quiet' sleep in octopuses is rhythmically interrupted by approximately 60-s bouts of pronounced body movements and rapid changes in skin patterning and texture6. We show that these bouts are homeostatically regulated, rapidly reversible and come with increased arousal threshold, representing a distinct 'active' sleep stage. Computational analysis of active sleep skin patterning reveals diverse dynamics through a set of patterns conserved across octopuses and strongly resembling those seen while awake. High-density electrophysiological recordings from the central brain reveal that the local field potential (LFP) activity during active sleep resembles that of waking. LFP activity differs across brain regions, with the strongest activity during active sleep seen in the superior frontal and vertical lobes, anatomically connected regions associated with learning and memory function7-10. During quiet sleep, these regions are relatively silent but generate LFP oscillations resembling mammalian sleep spindles11,12 in frequency and duration. The range of similarities with vertebrates indicates that aspects of two-stage sleep in octopuses may represent convergent features of complex cognition.

The self as part of the sensory ecology: how behavior affects sensation from the inside out.

Insects exhibit remarkable sensory and motor capabilities to successfully navigate their environment. As insects move, they activate sensory afferents. Hence, insects are inextricably part of their sensory ecology. Insects must correctly attribute self- versus external sources of sensory activation to make adaptive behavioral choices. This is achieved via corollary discharge circuits (CDCs), motor-to-sensory neuronal pathways providing predictive motor signals to sensory networks to coordinate sensory processing within the context of ongoing behavior. While CDCs provide predictive motor signals, their underlying mechanisms of action and functional consequences are diverse. Here, we describe inferred CDCs and identified corollary discharge interneurons (CDIs) in insects, highlighting their anatomical commonalities and our limited understanding of their synaptic integration into the nervous system. By using connectomics information, we demonstrate that the complexity with which identified CDIs integrate into the central nervous system (CNS) can be revealed.

A cold and quiet brain: mechanisms of insect CNS arrest at low temperatures.

Exposure to cold causes insects to enter a chill coma at species-specific temperatures and such temperature sensitivity contributes to geographic distribution and phenology. Coma results from abrupt spreading depolarization (SD) of neural tissue in the integrative centers of the central nervous system (CNS). SD abolishes neuronal signaling and the operation of neural circuits, like an off switch for the CNS. Turning off the CNS by allowing ion gradients to collapse will conserve energy and may offset negative consequences of temporary immobility. SD is modified by prior experience via rapid cold hardening (RCH) or cold acclimation that alter properties of Kv channels, Na+/K+-ATPase, and Na+/K+/2Cl- cotransporter. The stress hormone octopamine mediates RCH. Future progress depends on developing a more complete understanding of ion homeostasis in and of the insect CNS.

Cytokines as emerging regulators of central nervous system synapses.

Cytokines are key messengers by which immune cells communicate, and they drive many physiological processes, including immune and inflammatory responses. Early discoveries demonstrated that cytokines, such as the interleukin family members and TNF-α, regulate synaptic scaling and plasticity. Still, we continue to learn more about how these traditional immune system cytokines affect neuronal structure and function. Different cytokines shape synaptic function on multiple levels ranging from fine-tuning neurotransmission, to regulating synapse number, to impacting global neuronal networks and complex behavior. These recent findings have cultivated an exciting and growing field centered on the importance of immune system cytokines for regulating synapse and neural network structure and function. Here, we highlight the latest findings related to cytokines in the central nervous system and their regulation of synapse structure and function. Moreover, we explore how these mechanisms are becoming increasingly important to consider in diseases-especially those with a large neuroinflammatory component.

Gut Microbiome-Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders.

Gut microbiota includes a vast collection of microorganisms residing within the gastrointestinal tract. It is broadly recognized that the gut and brain are in constant bidirectional communication, of which gut microbiota and its metabolic production are a major component, and form the so-called gut microbiome-brain axis. Disturbances of microbiota homeostasis caused by imbalance in their functional composition and metabolic activities, known as dysbiosis, cause dysregulation of these pathways and trigger changes in the blood-brain barrier permeability, thereby causing pathological malfunctions, including neurological and functional gastrointestinal disorders. In turn, the brain can affect the structure and function of gut microbiota through the autonomic nervous system by regulating gut motility, intestinal transit and secretion, and gut permeability. Here, we examine data from the CAS Content Collection, the largest collection of published scientific information, and analyze the publication landscape of recent research. We review the advances in knowledge related to the human gut microbiome, its complexity and functionality, its communication with the central nervous system, and the effect of the gut microbiome-brain axis on mental and gut health. We discuss correlations between gut microbiota composition and various diseases, specifically gastrointestinal and mental disorders. We also explore gut microbiota metabolites with regard to their impact on the brain and gut function and associated diseases. Finally, we assess clinical applications of gut-microbiota-related substances and metabolites with their development pipelines. We hope this review can serve as a useful resource in understanding the current knowledge on this emerging field in an effort to further solving of the remaining challenges and fulfilling its potential.

Oligodendrocyte-derived transcellular signaling regulates axonal energy metabolism.

The unique morphology and functionality of central nervous system (CNS) neurons necessitate specialized mechanisms to maintain energy metabolism throughout long axons and extensive terminals. Oligodendrocytes (OLs) enwrap CNS axons with myelin sheaths in a multilamellar fashion. Apart from their well-established function in action potential propagation, OLs also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes consisting of proteins, lipids, and RNAs. OL-derived metabolic support is crucial for the maintenance of axonal integrity; its dysfunction has emerged as an important player in neurological disorders that are associated with axonal energy deficits and degeneration. In this review, we discuss recent advances in how these transcellular signaling pathways maintain axonal energy metabolism in health and neurological disorders.

Application of single-cell RNA sequencing in probing oligodendroglia heterogeneity and neurological disorders.

In the central nervous system, oligodendrocytes are highly specialized myelinating glial cells that originate from oligodendrocyte precursor cells. In the past, research centered on the oligodendrocyte development, myelination, and the role of oligodendrocyte lineage in neurological disorders. The emerging single-cell RNA sequencing technology is a new tool to specifically identify cell-types at the transcriptome level, and recently have also been used to investigate oligodendrocyte lineage-related issues. In this review, we summarize the recent developments of single-cell RNA sequencing technologies and their application in the oligodendroglia heterogeneity and neurological disorders, thereby providing new ideas and references for the utilization of single-cell RNA sequencing technology in the research field of oligodendrocyte lineage and neurological disorders.