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1.
Adv Neurobiol ; 36: 203-225, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468034

RESUMO

From the morphological point of view, the nervous system exhibits a fractal, self-similar geometry at various levels of observations, from single cells up to cell networks. From the functional point of view, it is characterized by a hierarchical organization in which self-similar structures (networks) of different miniaturizations are nested within each other. In particular, neuronal networks, interconnected to form neuronal systems, are formed by neurons, which operate thanks to their molecular networks, mainly having proteins as components that via protein-protein interactions can be assembled in multimeric complexes working as micro-devices. On this basis, the term "self-similarity logic" was introduced to describe a nested organization where, at the various levels, almost the same rules (logic) to perform operations are used. Self-similarity and self-similarity logic both appear to be intimately linked to the biophysical evidence for the nervous system being a pattern-forming system that can flexibly switch from one coherent state to another. Thus, they can represent the key concepts to describe its complexity and its concerted, holistic behavior.


Assuntos
Sistema Nervoso , Neurônios , Humanos , Neurônios/fisiologia , Lógica , Comunicação Celular
2.
Sci Rep ; 14(1): 5083, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429381

RESUMO

The ability to record every spike from every neuron in a behaving animal is one of the holy grails of neuroscience. Here, we report coming one step closer towards this goal with the development of an end-to-end pipeline that automatically tracks and extracts calcium signals from individual neurons in the cnidarian Hydra vulgaris. We imaged dually labeled (nuclear tdTomato and cytoplasmic GCaMP7s) transgenic Hydra and developed an open-source Python platform (TraSE-IN) for the Tracking and Spike Estimation of Individual Neurons in the animal during behavior. The TraSE-IN platform comprises a series of modules that segments and tracks each nucleus over time and extracts the corresponding calcium activity in the GCaMP channel. Another series of signal processing modules allows robust prediction of individual spikes from each neuron's calcium signal. This complete pipeline will facilitate the automatic generation and analysis of large-scale datasets of single-cell resolution neural activity in Hydra, and potentially other model organisms, paving the way towards deciphering the neural code of an entire animal.


Assuntos
Hydra , Animais , Hydra/fisiologia , Cálcio , Sistema Nervoso , Animais Geneticamente Modificados
3.
Eur J Med Res ; 29(1): 174, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491477

RESUMO

O-GlcNAcylation is a unique monosaccharide modification that is ubiquitously present in numerous nucleoplasmic and mitochondrial proteins. The hexosamine biosynthesis pathway (HBP), which is a key branch of glycolysis, provides the unique sugar donor UDP-GlcNAc for the O-GlcNAc modification. Thus, HBP/O-GlcNAcylation can act as a nutrient sensor to perceive changes in nutrient levels and trigger O-GlcNAc modifications of functional proteins in cellular (patho-)physiology, thereby regulating diverse metabolic processes. An imbalance in O-GlcNAcylation has been shown to be a pathogenic contributor to dysfunction in metabolic diseases, including type 2 diabetes, cancer, and neurodegeneration. However, under acute stress conditions, protein O-GlcNAc modification exhibits rapid and transient upregulation, which is strongly correlated with stress tolerance and cell survival. In this context, we discuss the metabolic, pharmacological and genetic modulation of HBP/O-GlcNAc modification in the biological system, the beneficial role of O-GlcNAcylation in regulating stress tolerance for cardioprotection, and neuroprotection, which is a novel and rapidly growing field. Current evidence suggests that transient activation of the O-GlcNAc modification represents a potent pro-survival signalling pathway and may provide a promising strategy for stress-related disorder therapy.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Glicosilação , Coração , Processamento de Proteína Pós-Traducional , Sistema Nervoso
4.
Gut Microbes ; 16(1): 2327409, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38488630

RESUMO

The gut microbiota exerts a mutualistic interaction with the host in a fragile ecosystem and the host intestinal, neural, and immune cells. Perturbations of the gastrointestinal track composition after stress have profound consequences on the central nervous system and the immune system. Reciprocally, brain signals after stress affect the gut microbiota highlighting the bidirectional communication between the brain and the gut. Here, we focus on the potential role of inflammation in mediating stress-induced gut-brain changes and discuss the impact of several immune cells and inflammatory molecules of the gut-brain dialogue after stress. Understanding the impact of microbial changes on the immune system after stress might provide new avenues for therapy.


Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Microbioma Gastrointestinal/fisiologia , Encéfalo/fisiologia , Sistema Nervoso , Inflamação
5.
Mol Brain ; 17(1): 13, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413970

RESUMO

The AP-2 transcription factors are crucial for regulating sleep in both vertebrate and invertebrate animals. In mice, loss of function of the transcription factor AP-2ß (TFAP2B) reduces non-rapid eye movement (NREM) sleep. When and where TFAP2B functions, however, is unclear. Here, we used the Cre-loxP system to generate mice in which Tfap2b was specifically deleted in the nervous system during development and mice in which neuronal Tfap2b was specifically deleted postnatally. Both types of mice exhibited reduced NREM sleep, but the nervous system-specific deletion of Tfap2b resulted in more severe sleep phenotypes accompanied by defective light entrainment of the circadian clock and stereotypic jumping behavior. These findings indicate that TFAP2B in postnatal neurons functions at least partly in sleep regulation and imply that TFAP2B also functions either at earlier stages or in additional cell types within the nervous system.


Assuntos
Fator de Transcrição AP-2 , Fatores de Transcrição , Animais , Camundongos , Sistema Nervoso/metabolismo , Sono , Fator de Transcrição AP-2/genética , Fator de Transcrição AP-2/metabolismo
6.
BMC Musculoskelet Disord ; 25(1): 140, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355438

RESUMO

BACKGROUND: Quantitative sensory testing (QST) offers information regarding underlying mechanisms contributing to chronic pain (CP) in adults with musculoskeletal disorders. This review examined the use of QST measures in adults with CP following participation in a combined exercise and psychological intervention. METHODS: The review was conducted in accordance with the PRISMA guidelines. Five databases were searched from inception to November 2022. All study designs which evaluated the effects of a combined exercise and psychological treatment on measures of nervous system sensitivity in adults with chronic musculoskeletal pain were included. RESULTS: A total of 13 studies met the selection criteria, 10 of which were included in a meta-analysis. Local pressure pain thresholds were the most frequently used measure (n = 12 studies). Meta-analysis revealed statistically significantly improvements in favour of the combined exercise and psychological intervention group, compared to a control group, for local pressure pain threshold measures [SMD = 0.44, 95% CI 0.08-0.81, I2 = 84%], pain intensity scores [SMD=-0.89, 95% CI -1.66- -0.13, I2 = 94%] and the Central Sensitisation Inventory [SMD=-0.69, 95% CI -1.37- -0.02, I2 = 87%]. There were no significant differences found between groups for remote pressure pain thresholds, temporal summation or conditioned pain modulation. CONCLUSIONS: The results suggest that a combined exercise and psychological intervention may lead to greater improvements in local pressure pain threshold, pain intensity and Central Sensitisation Inventory scores when compared to a control intervention in adults with CP, however these findings must be interpreted with caution as a large degree of heterogeneity was present in these results (I2: 84-94%). Further large, longitudinal studies are required using standardised QST measurement procedures and patient reported outcome measures to explore changes in nervous system sensitisation. TRIAL REGISTRATION: This systematic review is registered with PROSPERO, ID Number CRD42022380464.


Assuntos
Dor Crônica , Dor Musculoesquelética , Adulto , Humanos , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/terapia , Dor Crônica/diagnóstico , Dor Crônica/terapia , Limiar da Dor/fisiologia , Exercício Físico , Sistema Nervoso
7.
Neural Dev ; 19(1): 3, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383501

RESUMO

BACKGROUND: The evolutionary origins of animal nervous systems remain contentious because we still have a limited understanding of neural development in most major animal clades. Annelids - a species-rich group with centralised nervous systems - have played central roles in hypotheses about the origins of animal nervous systems. However, most studies have focused on adults of deeply nested species in the annelid tree. Recently, Owenia fusiformis has emerged as an informative species to reconstruct ancestral traits in Annelida, given its phylogenetic position within the sister clade to all remaining annelids. METHODS: Combining immunohistochemistry of the conserved neuropeptides FVamide-lir, RYamide-lir, RGWamide-lir and MIP-lir with gene expression, we comprehensively characterise neural development from larva to adulthood in Owenia fusiformis. RESULTS: The early larval nervous system comprises a neuropeptide-rich apical organ connected through peripheral nerves to a prototroch ring and the chaetal sac. There are seven sensory neurons in the prototroch. A bilobed brain forms below the apical organ and connects to the ventral nerve cord of the developing juvenile. During metamorphosis, the brain compresses, becoming ring-shaped, and the trunk nervous system develops several longitudinal cords and segmented lateral nerves. CONCLUSIONS: Our findings reveal the formation and reorganisation of the nervous system during the life cycle of O. fusiformis, an early-branching annelid. Despite its apparent neuroanatomical simplicity, this species has a diverse peptidergic nervous system, exhibiting morphological similarities with other annelids, particularly at the larval stages. Our work supports the importance of neuropeptides in animal nervous systems and highlights how neuropeptides are differentially used throughout development.


Assuntos
Anelídeos , Neuropeptídeos , Poliquetos , Animais , Filogenia , Anelídeos/anatomia & histologia , Anelídeos/genética , Sistema Nervoso/metabolismo , Poliquetos/anatomia & histologia , Poliquetos/genética , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Larva
8.
Arch Insect Biochem Physiol ; 115(2): e22089, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38409869

RESUMO

Insecticide mode of action studies provide insights into how new insecticidal actives function and contribute to assessing safety to humans and nontarget organisms. Insect cell lines that express potential target sites can serve as valuable tools in this effort. In this paper, we report on the influence of two signaling molecules on protein expression in a nervous system cell line established from Spodoptera frugiperda (Bayer/BCIRL-SfNS2-0714-TR). We selected this line because we established it in our laboratory and we are experienced in using it. Cells were exposed to the insect developmental hormone (1 µg/mL 20-hydroxyecdysone, 20E) and/or a cyclooxygenase (COX) inhibitor (25 µM indomethacin, INDO; inhibits prostaglandin [PG] biosynthesis) for 24 h (Day 2), 72 h (Day 4), or 120 h (Day 6). We selected a PG biosynthesis inhibitor because PGs act in many aspects of insect biology, such as embryonic development, immunity, and protein phosphorylation. We selected the developmental hormone, 20E, because it also acts in fundamental aspects of insect biology. We identified specific proteins via in silico analysis. Changes in protein expression levels were determined using liquid chromatography-mass spectrometry (MS) + MS-MS. The largest number of changes in protein expression occurred on Day 2. The combination of 20E plus INDO led to 222 differentially expressed proteins, which documents the deep significance of PGs and 20E in insect biology. 20E and, separately, INDO led to changes in 30 proteins each (p value < 0.01; >2X or <0.5X-fold changes). We recorded changes in the expression of 9 or 12 proteins (20E), 10 or 6 proteins (INDO), and 21 or 20 proteins (20E + INDO) on D4 and D6, respectively. While the cell line was established from neuronal tissue, the differentially expressed proteins act in a variety of fundamental cell processes. In this paper, we moved beyond a list of proteins by providing detailed, Gene Ontology term analyses and enrichment, which offers an in-depth understanding of the influence of these treatments on the SfNS2 cells. Because proteins are active components of cell physiology in their roles as enzymes, receptors, elements of signaling transduction pathways, and cellular structures, changes in their expression levels under the influence of signaling molecules provide insights into their function in insect cell physiology.


Assuntos
Ecdisterona , Indometacina , Humanos , Animais , Ecdisterona/farmacologia , Ecdisterona/metabolismo , Spodoptera/metabolismo , Insetos/metabolismo , Linhagem Celular , Hormônios , Sistema Nervoso/metabolismo , Proteínas de Insetos/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-38366688

RESUMO

Procyanidins are gaining attention due to their potential health benefits. We found that cacao liquor procyanidin (CLPr) from Theobroma cacao seeds increased the lifespan of Caenorhabditis elegans, a representative model organism for aging studies. The genetic dependence of the lifespan-extending effect of CLPr was consistent with that of blueberry procyanidin, which is dependent on unc-43, osr-1, sek-1, and mev-1, but not on daf-16, sir-2.1, or skn-1. The lifespan-extending effect of CLPr was inhibited by neuron-specific RNA interference (RNAi) targeting unc-43 and pmk-1, and in worms with loss-of-function mutations in the odr-3, odr-1, or tax-4 genes, which are essential in sensory neurons, including AWC neurons. It was also inhibited in worms in which AWC neurons or AIB interneurons had been eliminated, and in worms with loss-of-function mutations in eat-4 or glr-1, which are responsible for glutamatergic synaptic transmission. These results suggest that the lifespan-extending effect of CLPr is dependent on the nervous system. In addition, it also requires unc-43 and pmk-1 expression in nonneuronal cells, as demonstrated by the experiments with RNAi in wild-type worms, the neuronal cells of which are not affected by systemic RNAi. The osr-1 gene is expressed in hypodermal and intestinal cells and regulates the response to osmotic stress along with unc-43/calcium/calmodulin-dependent protein kinase II and the p38 mitogen-activated protein kinase pathway. Consistent with this, CLPr improved osmotic stress tolerance in an unc-43- and pmk-1-dependent manner, and it was also dependent on AWC neurons. The lifespan-extending and osmotic-tolerance-improving activities were attributed to procyanidins with a tetrameric or higher-order oligomeric structure.


Assuntos
Biflavonoides , Cacau , Proteínas de Caenorhabditis elegans , Catequina , Proantocianidinas , Animais , Caenorhabditis elegans/fisiologia , Longevidade/fisiologia , Proantocianidinas/farmacologia , Proantocianidinas/metabolismo , Cacau/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/farmacologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Sistema Nervoso/metabolismo
10.
Sci Rep ; 14(1): 3805, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360907

RESUMO

Secreted proteins of the Noggin family serve as pivotal regulators of early development and cell differentiation in all multicellular animals, including vertebrates. Noggin1 was identified first among all Noggins. Moreover, it was described as the first known embryonic inducer specifically secreted by the Spemann organizer and capable of inducing a secondary body axis when expressed ectopically. In the classical default model of neural induction, Noggin1 is presented as an antagonist of BMP signalling, playing a role as a neural inducer. Additionally, Noggin1 is involved in the dorsalization of embryonic mesoderm and later controls the differentiation of various tissues, including muscles, bones, and neural crest derivatives. Hitherto, noggin1 was found in all studied vertebrates. Here, we report the loss of noggin1 in elasmobranchs (sharks, rays and skates), which is a unique case among vertebrates. noggin2 and noggin4 retained in this group and studied in the embryos of the grey bamboo shark Chiloscyllium griseum revealed similarities in expression patterns and functional properties with their orthologues described in other vertebrates. The loss of noggin1 in elasmobranchs may be associated with histological features of the formation of their unique internal cartilaginous skeleton, although additional research is required to establish functional connections between these events.


Assuntos
Sistema Nervoso , Tubarões , Animais , Sistema Nervoso/metabolismo , Proteínas/metabolismo , Desenvolvimento Embrionário/genética , Diferenciação Celular
11.
J Morphol ; 285(2): e21672, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38361267

RESUMO

The digenean complex life cycle includes various morphological forms with different locomotory and behavioral activities, and the functional specialization of their nervous system is of importance for the transmission of these parasites. Adult digeneans acquire many adaptive features associated with the final settlement in a vertebrate host. Our study describes the general morphology and ultrastructure of the nervous system of the adult renicolid digenean Renicola parvicaudatus parasitizing the renal tubules of herring gulls. Using immunocytochemical and electron microscopic methods, we identified the distinctive characteristics of ganglia and synapses in the studied species. A comparative analysis of the organization of the nervous system of adult individuals and their continuously-swimming stylet cercariae revealed a number of stage-related differences in the composition of ganglia, the distribution of serotonin- and FMRFamide-immunoreactive neurons, the cytomorphology of neuron somata and free sensory endings. Thus, in adults, the presence of FMRFamide-positive neuron somata, accessory muscle bundles in the ganglionic cortex, and eight types of neuronal vesicles was detected, but no glia-like elements were identified. Their neurons are characterized by a larger volume of cytoplasm and also show greater ultrastructural diversity. Although the sensory papillae of adults do not vary in their external morphology as much as those of larvae, their sensory bulbs are more diverse in cytomorphology. Following our previous data on the "support" cell processes related to various tissues of the larvae and considered as glia-like structures, we also briefly present the identified features of the parenchyma, attachment organs and excretory system of adult individuals. The excretory system of adult R. parvicaudatus is characterized by the presence of unique terminal cells with several flame tufts, which are not typical either for the larvae of this species or for other digeneans studied so far. We also used molecular phylogenetic analysis to clarify species identification.


Assuntos
Sistema Nervoso , Trematódeos , Animais , FMRFamida , Filogenia , Sistema Nervoso/anatomia & histologia , Trematódeos/anatomia & histologia , Neurônios/ultraestrutura , Sinapses/ultraestrutura , Larva
12.
Psychopharmacology (Berl) ; 241(3): 627-635, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38363344

RESUMO

RATIONALE: Although the study of emotions can look back to over 100 years of research, it is unclear which information the brain uses to construct the subjective experience of an emotion. OBJECTIVE: In the current study, we assess the role of the peripheral and central adrenergic system in this respect. METHODS: Healthy volunteers underwent a double inhalation of 35% CO2, which is a well-validated procedure to induce an intense emotion, namely panic. In a randomized, cross-over design, 34 participants received either a ß1-blocker acting selectively in the peripheral nervous system (atenolol), a ß1-blocker acting in the peripheral and central nervous system (metoprolol), or a placebo before the CO2 inhalation. RESULTS: Heart rate and systolic blood pressure were reduced in both ß-blocker conditions compared to placebo, showing effective inhibition of the adrenergic tone. Nevertheless, the subjective experience of the induced panic was the same in all conditions, as measured by self-reported fear, discomfort, and panic symptom ratings. CONCLUSIONS: These results indicate that information from the peripheral and central adrenergic system does not play a major role in the construction of the subjective emotion.


Assuntos
Antagonistas Adrenérgicos beta , Dióxido de Carbono , Emoções , Sistema Nervoso , Pânico , Humanos , Antagonistas Adrenérgicos beta/farmacologia , Dióxido de Carbono/farmacologia , Emoções/efeitos dos fármacos , Emoções/fisiologia , Medo/efeitos dos fármacos , Medo/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Pânico/efeitos dos fármacos , Pânico/fisiologia , Sistema Nervoso/efeitos dos fármacos
14.
Development ; 151(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38358799

RESUMO

The Wnt/ß-catenin signaling governs anterior-posterior neural patterning during development. Current human pluripotent stem cell (hPSC) differentiation protocols use a GSK3 inhibitor to activate Wnt signaling to promote posterior neural fate specification. However, GSK3 is a pleiotropic kinase involved in multiple signaling pathways and, as GSK3 inhibition occurs downstream in the signaling cascade, it bypasses potential opportunities for achieving specificity or regulation at the receptor level. Additionally, the specific roles of individual FZD receptors in anterior-posterior patterning are poorly understood. Here, we have characterized the cell surface expression of FZD receptors in neural progenitor cells with different regional identity. Our data reveal unique upregulation of FZD5 expression in anterior neural progenitors, and this expression is downregulated as cells adopt a posterior fate. This spatial regulation of FZD expression constitutes a previously unreported regulatory mechanism that adjusts the levels of ß-catenin signaling along the anterior-posterior axis and possibly contributes to midbrain-hindbrain boundary formation. Stimulation of Wnt/ß-catenin signaling in hPSCs, using a tetravalent antibody that selectively triggers FZD5 and LRP6 clustering, leads to midbrain progenitor differentiation and gives rise to functional dopaminergic neurons in vitro and in vivo.


Assuntos
Receptores Frizzled , Quinase 3 da Glicogênio Sintase , beta Catenina , Humanos , beta Catenina/metabolismo , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Mesencéfalo , Sistema Nervoso/metabolismo , Via de Sinalização Wnt , Animais , Ratos
15.
Elife ; 122024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411140

RESUMO

Eukaryotes respond to secreted metabolites from the microbiome. However, little is known about the effects of exposure to volatiles emitted by microbes or in the environment that we are exposed to over longer durations. Using Drosophila melanogaster, we evaluated a yeast-emitted volatile, diacetyl, found at high levels around fermenting fruits where they spend long periods of time. Exposure to the diacetyl molecules in headspace alters gene expression in the antenna. In vitro experiments demonstrated that diacetyl and structurally related volatiles inhibited conserved histone deacetylases (HDACs), increased histone-H3K9 acetylation in human cells, and caused changes in gene expression in both Drosophila and mice. Diacetyl crosses the blood-brain barrier and exposure caused modulation of gene expression in the mouse brain, therefore showing potential as a neuro-therapeutic. Using two separate disease models previously known to be responsive to HDAC inhibitors, we evaluated the physiological effects of volatile exposure. Diacetyl exposure halted proliferation of a neuroblastoma cell line in culture. Exposure to diacetyl vapors slowed progression of neurodegeneration in a Drosophila model for Huntington's disease. These changes strongly suggest that certain volatiles in the surroundings can have profound effects on histone acetylation, gene expression, and physiology in animals.


Assuntos
Drosophila melanogaster , Histona Desacetilases , Humanos , Camundongos , Animais , Histona Desacetilases/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Histonas/metabolismo , Odorantes , Diacetil , Inibidores de Histona Desacetilases/farmacologia , Drosophila/genética , Sistema Nervoso/metabolismo , Expressão Gênica , Acetilação
17.
Genes Genet Syst ; 98(6): 321-336, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38220159

RESUMO

In the course of evolution, the most highly developed organ is likely the brain, which has become more complex over time and acquired diverse forms and functions in different species. In particular, mammals have developed complex and high-functioning brains, and it has been reported that several genes derived from retroviruses were involved in mammalian brain evolution, that is, generating the complexity of the nervous system. Especially, the sushi-ichi-related retrotransposon homolog (SIRH)/retrotransposon gag-like (RTL) genes have been suggested to play a role in the evolutionary processes shaping brain morphology and function in mammals. Genetic mutation and altered expression of genes are linked to neurological disorders, highlighting how the acquisition of virus-derived genes in mammals has both driven brain evolution and imposed a susceptibility to diseases. This review provides an overview of the functions, diversity, evolution and diseases associated with SIRH/RTL genes in the nervous system. The contribution of retroviruses to brain evolution is an important research topic in evolutionary biology and neuroscience, and further insights are expected to be gained through future studies.


Assuntos
Retroelementos , Retroviridae , Animais , Retroviridae/genética , Retroelementos/genética , Mamíferos/genética , Sistema Nervoso , Evolução Molecular
18.
Curr Osteoporos Rep ; 22(1): 205-216, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38236509

RESUMO

PURPOSE OF REVIEW: Despite advances in orthopedics, there remains a need for therapeutics to hasten fracture healing. However, little focus is given to the role the nervous system plays in regulating fracture healing. This paucity of information has led to an incomplete understanding of fracture healing and has limited the development of fracture therapies that integrate the importance of the nervous system. This review seeks to illuminate the integral roles that the nervous system plays in fracture healing. RECENT FINDINGS: Preclinical studies explored several methodologies for ablating peripheral nerves to demonstrate ablation-induced deficits in fracture healing. Conversely, activation of peripheral nerves via the use of dorsal root ganglion electrical stimulation enhanced fracture healing via calcitonin gene related peptide (CGRP). Investigations into TLR-4, TrkB agonists, and nerve growth factor (NGF) expression provide valuable insights into molecular pathways influencing bone mesenchymal stem cells and fracture repair. Finally, there is continued research into the connections between pain and fracture healing with findings suggesting that anti-NGF may be able to block pain without affecting healing. This review underscores the critical roles of the central nervous system (CNS), peripheral nervous system (PNS), and autonomic nervous system (ANS) in fracture healing, emphasizing their influence on bone cells, neuropeptide release, and endochondral ossification. The use of TBI models contributes to understanding neural regulation, though the complex influence of TBI on fracture healing requires further exploration. The review concludes by addressing the neural connection to fracture pain. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.


Assuntos
Inteligência Artificial , Consolidação da Fratura , Humanos , Consolidação da Fratura/fisiologia , Peptídeo Relacionado com Gene de Calcitonina , Dor , Sistema Nervoso/metabolismo
19.
Ecotoxicol Environ Saf ; 271: 115965, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244513

RESUMO

Glyphosate (GLP) and GLP-based herbicides (GBHs), such as polyethoxylated tallow amine-based GLP surfactants (GLP-SH), developed in the late 70', have become the most popular and controversial agrochemicals ever produced. Nowadays, GBHs have reached 350 million hectares of crops in over 140 countries, with an annual turnover of 5 billion and 11 billion USD in the U.S.A. and worldwide, respectively. Because of the highly efficient inhibitory activity of GLP targeted to the 5-enolpyruvylshikimate-3-phosphate synthase pathway, present in plants and several bacterial strains, the GLP-resistant crop-based genetic agricultural revolution has decreased famine and improved the costs and quality of living in developing countries. However, this progress has come at the cost of the 50-year GBH overuse, leading to environmental pollution, animal intoxication, bacterial resistance, and sustained occupational exposure of the herbicide farm and companies' workers. According to preclinical and clinical studies covered in the present review, poisoning with GLP, GLP-SH, and GBHs devastatingly affects gut microbiota and the microbiota-gut-brain (MGB) axis, leading to dysbiosis and gastrointestinal (GI) ailments, as well as immunosuppression and inappropriate immunostimulation, cholinergic neurotransmission dysregulation, neuroendocrinal system disarray, and neurodevelopmental and neurobehavioral alterations. Herein, we mainly focus on the contribution of gut microbiota (GM) to neurological impairments, e.g., stroke and neurodegenerative and neuropsychiatric disorders. The current review provides a comprehensive introduction to GLP's microbiological and neurochemical activities, including deviation of the intestinal Firmicutes-to-Bacteroidetes ratio, acetylcholinesterase inhibition, excitotoxicity, and mind-altering processes. Besides, it summarizes and critically discusses recent preclinical studies and clinical case reports concerning the harmful impacts of GBHs on the GI tract, MGB axis, and nervous system. Finally, an insightful comparison of toxic effects caused by GLP, GBH-SH, and GBHs is presented. To this end, we propose a first-to-date survey of clinical case reports on intoxications with these herbicides.


Assuntos
Herbicidas , Exposição Ocupacional , Animais , Glicina/toxicidade , Eixo Encéfalo-Intestino , Acetilcolinesterase , Herbicidas/toxicidade , Sistema Nervoso
20.
Int J Mol Sci ; 25(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38203763

RESUMO

Vitamin B12 (VitB12) is a micronutrient and acts as a cofactor for fundamental biochemical reactions: the synthesis of succinyl-CoA from methylmalonyl-CoA and biotin, and the synthesis of methionine from folic acid and homocysteine. VitB12 deficiency can determine a wide range of diseases, including nervous system impairments. Although clinical evidence shows a direct role of VitB12 in neuronal homeostasis, the molecular mechanisms are yet to be characterized in depth. Earlier investigations focused on exploring the biochemical shifts resulting from a deficiency in the function of VitB12 as a coenzyme, while more recent studies propose a broader mechanism, encompassing changes at the molecular/cellular levels. Here, we explore existing study models employed to investigate the role of VitB12 in the nervous system, including the challenges inherent in replicating deficiency/supplementation in experimental settings. Moreover, we discuss the potential biochemical alterations and ensuing mechanisms that might be modified at the molecular/cellular level (such as epigenetic modifications or changes in lysosomal activity). We also address the role of VitB12 deficiency in initiating processes that contribute to nervous system deterioration, including ROS accumulation, inflammation, and demyelination. Consequently, a complex biological landscape emerges, requiring further investigative efforts to grasp the intricacies involved and identify potential therapeutic targets.


Assuntos
Depressores do Sistema Nervoso Central , Deficiência de Vitamina B 12 , Humanos , Vitamina B 12 , Modelos Biológicos , Biotina , Sistema Nervoso
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