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1.
Sci Adv ; 10(36): eadn3259, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39231237

RESUMO

Cerebrospinal fluid (CSF) is responsible for maintaining brain homeostasis through nutrient delivery and waste removal for the central nervous system (CNS). Here, we demonstrate extensive CSF flow throughout the peripheral nervous system (PNS) by tracing distribution of multimodal 1.9-nanometer gold nanoparticles, roughly the size of CSF circulating proteins, infused within the lateral cerebral ventricle (a primary site of CSF production). CSF-infused 1.9-nanometer gold transitions from CNS to PNS at root attachment/transition zones and distributes through the perineurium and endoneurium, with ultimate delivery to axoplasm of distal peripheral nerves. Larger 15-nanometer gold fails to transit from CNS to PNS and instead forms "dye-cuffs," as predicted by current dogma of CSF restriction within CNS, identifying size limitations in central to peripheral flow. Intravenous 1.9-nanometer gold is unable to cross the blood-brain/nerve barrier. Our findings suggest that CSF plays a consistent role in maintaining homeostasis throughout the nervous system with implications for CNS and PNS therapy and neural drug delivery.


Assuntos
Líquido Cefalorraquidiano , Nervos Periféricos , Animais , Líquido Cefalorraquidiano/metabolismo , Líquido Cefalorraquidiano/fisiologia , Nervos Periféricos/fisiologia , Ouro/química , Sistema Nervoso Periférico/fisiologia , Nanopartículas Metálicas/química , Sistema Nervoso Central/fisiologia , Sistema Nervoso Central/metabolismo , Barreira Hematoencefálica/metabolismo , Ratos , Camundongos
2.
G3 (Bethesda) ; 14(9)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-38996053

RESUMO

Despite increasing in mass approximately 100-fold during larval life, the Drosophila CNS maintains its characteristic form. Dynamic interactions between the overlying basement membrane and underlying surface glia are known to regulate CNS structure in Drosophila, but the genes and pathways that establish and maintain CNS morphology during development remain poorly characterized. To identify genes that regulate CNS shape in Drosophila, we conducted an EMS-based, forward genetic screen of the second chromosome, uncovered 50 mutations that disrupt CNS structure, and mapped these alleles to 17 genes. Analysis of whole genome sequencing data wedded to genetic studies uncovered the affected gene for all but 1 mutation. Identified genes include well-characterized regulators of tissue shape, like LanB1, viking, and Collagen type IV alpha1, and previously characterized genes, such as Toll-2 and Rme-8, with no known role in regulating CNS structure. We also uncovered that papilin and C1GalTA likely act in the same pathway to regulate CNS structure and found that the fly homolog of a glucuronosyltransferase, B4GAT1/LARGE1, that regulates Dystroglycan function in mammals is required to maintain CNS shape in Drosophila. Finally, we show that the senseless-2 transcription factor is expressed and functions specifically in surface glia found on peripheral nerves but not in the CNS to govern CNS structure, identifying a gene that functionally subdivides a glial subtype along the peripheral-central axis. Future work on these genes should clarify the genetic mechanisms that ensure the homeostasis of CNS form during development.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Mutação , Fatores de Transcrição , Animais , Alelos , Sistema Nervoso Central/metabolismo , Drosophila/genética , Drosophila melanogaster/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Testes Genéticos , Neuroglia/metabolismo , Sistema Nervoso Periférico/metabolismo , Fenótipo , Fatores de Transcrição/metabolismo
3.
Sensors (Basel) ; 24(14)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39066092

RESUMO

(1) Background: Restoring arm and hand function is one of the priorities of people with cervical spinal cord injury (cSCI). Noninvasive electromagnetic neuromodulation is a current approach that aims to improve upper-limb function in individuals with SCI. The aim of this study is to review updated information on the different applications of noninvasive electromagnetic neuromodulation techniques that focus on restoring upper-limb functionality and motor function in people with cSCI. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used to structure the search protocol. A systematic review of the literature was performed in three databases: the Cochrane Library, PubMed, and Physiotherapy Evidence Database (PEDro). (3) Results: Twenty-five studies were included: four were on transcranial magnetic stimulation (TMS), four on transcranial direct current stimulation (tDCS), two on transcutaneous spinal cord stimulation (tSCS), ten on functional electrical stimulation (FES), four on transcutaneous electrical nerve stimulation (TENS), and one on neuromuscular stimulation (NMS). The meta-analysis could not be completed due to a lack of common motor or functional evaluations. Finally, we realized a narrative review of the results, which reported that noninvasive electromagnetic neuromodulation combined with rehabilitation at the cerebral or spinal cord level significantly improved upper-limb functionality and motor function in cSCI subjects. Results were significant compared with the control group when tSCS, FES, TENS, and NMS was applied. (4) Conclusions: To perform a meta-analysis and contribute to more evidence, randomized controlled trials with standardized outcome measures for the upper extremities in cSCI are needed, even though significant improvement was reported in each non-invasive electromagnetic neuromodulation study.


Assuntos
Traumatismos da Medula Espinal , Estimulação Magnética Transcraniana , Extremidade Superior , Humanos , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/terapia , Extremidade Superior/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Sistema Nervoso Periférico/fisiopatologia , Sistema Nervoso Central/fisiopatologia , Sistema Nervoso Central/efeitos da radiação , Sistema Nervoso Central/fisiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Estimulação Transcraniana por Corrente Contínua/métodos , Medula Cervical/lesões
4.
AJNR Am J Neuroradiol ; 45(8): 1153-1161, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-38991773

RESUMO

BACKGROUND AND PURPOSE: After repeat administration of gadolinium-based contrast agents (GBCAs), the association between gadolinium retention in the central and peripheral nervous systems and the main manifestations of myelopathy and progressive neurologic symptoms remains unclear. We investigated the effects of the repeat administration of GBCAs on gadolinium retention in the central and peripheral nervous systems and the sensory, cognitive, and athletic implications. MATERIALS AND METHODS: Forty-eight male Wistar rats (6 weeks of age) were randomly divided into 4 experimental groups (12 rats in each group): the gadodiamide group (linear and nonionic GBCAs), the gadopentetate dimeglumine group (linear and ionic GBCAs), the gadoterate meglumine group (macrocyclic and ionic GBCAs), and the control group (0.9% saline solution). The brains of the rats were scanned using 9.4T MRI. Sensory behavioral tests were performed to assess the effect of GBCAs on pain sensitivity function. Gadolinium deposition in the brain, spinal cord, and peripheral nerves was determined by inductively coupled plasma mass-spectrometry. Transmission electron microscopy was used to observe the microscopic distribution of gadolinium after deposition in the spinal cord. The histopathologic features in the spinal cord were analyzed by H&E staining, Nissl staining, glial fibrillary acidic protein staining, and neuron-specific enolase staining after administration of GBCAs. RESULTS: All GBCAs resulted in gadolinium deposition in the central and peripheral nerve tissues, with the highest deposition in the sciatic nerve tissue (mean, 62.86 [SD, 12.56] nmol/g). Decreased muscle power, impairment of spatial cognitive function power, and pain hypersensitivity to thermal and mechanical stimuli were observed after exposure to gadodiamide. At the spinal cord, transmission electron microscopy found that the region of gadolinium depositions had a spheric structure similar to "sea urchins" and was mainly located near the vascular basement membrane. CONCLUSIONS: Multiple injections of GBCAs caused gadolinium deposition in the brain, spinal cord, and peripheral nerves, especially in the spinal cords of the gadodiamide group. Gadodiamide led to pain hypersensitivity and decreased muscle power and cognitive ability. For the patients who are hypersensitive to pain and need multiple MRI examinations, we recommend using macrocyclic GBCAs and the lowest dose possible.


Assuntos
Meios de Contraste , Gadolínio , Ratos Wistar , Animais , Meios de Contraste/farmacocinética , Masculino , Ratos , Gadolínio/farmacocinética , Imageamento por Ressonância Magnética/métodos , Cognição/efeitos dos fármacos , Gadolínio DTPA/farmacocinética , Gadolínio DTPA/administração & dosagem , Sistema Nervoso Periférico/efeitos dos fármacos , Sistema Nervoso Periférico/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Medula Espinal/metabolismo , Medula Espinal/efeitos dos fármacos , Sistema Nervoso Central/diagnóstico por imagem , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos
5.
J Steroid Biochem Mol Biol ; 243: 106590, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39053702

RESUMO

Neuroactive steroids (i.e., sex steroid hormones and neurosteroids) are important physiological regulators of nervous function and potential neuroprotective agents for neurodegenerative and psychiatric disorders. Sex is an important component of such effects. However, even if fluctuations in sex steroid hormone level during the menstrual cycle are associated with neuropathological events in some women, the neuroactive steroid pattern in the brain across the ovarian cycle has been poorly explored. Therefore, we assessed the levels of pregnenolone, progesterone, and its metabolites (i.e., dihydroprogesterone, allopregnanolone and isoallopregnanolone), dehydroepiandrosterone, testosterone and its metabolites (i.e., dihydrotestosterone, 3α-diol and 17ß-estradiol) across the rat ovarian cycle to determine whether their plasma fluctuations are similar to those occurring in the central (i.e., hippocampus and cerebral cortex) and peripheral (i.e., sciatic nerve) nervous system. Data obtained indicate that the plasma pattern of these molecules generally does not fully reflect the events occurring in the nervous system. In addition, for some neuroactive steroid levels, the pattern is not identical between the two brain regions and between the brain and peripheral nerves. Indeed, with the exception of progesterone, all other neuroactive steroids assessed here showed peculiar regional differences in their pattern of fluctuation in the nervous system during the estrous cycle. These observations may have important diagnostic and therapeutic consequences for neuropathological events influenced by the menstrual cycle.


Assuntos
Ciclo Estral , Neuroesteroides , Progesterona , Animais , Feminino , Ratos , Neuroesteroides/metabolismo , Neuroesteroides/sangue , Progesterona/sangue , Progesterona/metabolismo , Sistema Nervoso Periférico/metabolismo , Pregnenolona/sangue , Pregnenolona/metabolismo , Nervo Isquiático/metabolismo , Sistema Nervoso Central/metabolismo , Hipocampo/metabolismo , Desidroepiandrosterona/sangue , Desidroepiandrosterona/metabolismo , Testosterona/sangue , Testosterona/metabolismo , Ratos Sprague-Dawley , Córtex Cerebral/metabolismo , Estradiol/sangue , Estradiol/metabolismo
6.
Tissue Cell ; 88: 102429, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833939

RESUMO

Neuronal injuries, as one of the consequences of sports-related incidents, exert a profound influence on the athletes' future, potentially leading to complete immobility and impeding their athletic pursuits. In cases of severe damage inflicted upon the spinal cord (SC) and peripheral nervous systems (PNS), the regenerative process is notably compromised, rendering it essentially inefficient. Among the pivotal therapeutic approaches for the enhancement and prevention of secondary SC injuries (SCI), stem cell transplantation (SCT) stands out prominently. Stem cells, whether directly involved in replacement and reconstruction or indirectly through modification and secretion of crucial bioenvironmental factors, engage in the intricate process of tissue regeneration. Stem cells, through the secretion of neurotrophic factors (NTFs) (aiming to modulate the immune system), reduction of inflammation, axonal growth stimulation, and myelin formation, endeavor to facilitate the regeneration of damaged SC tissue. The fundamental challenges of this approach encompass the proper selection of suitable stem cell candidates for transplantation and the establishment of an appropriate microenvironment conducive to SC repair. In this article, an attempt has been made to explore sports-related injuries, particularly SCI, to comprehensively review innovative methods for treating SCI, and to address the existing challenges. Additionally, some of the stem cells used in neural injuries and the process of their utilization have been discussed.


Assuntos
Traumatismos em Atletas , Traumatismos da Medula Espinal , Transplante de Células-Tronco , Humanos , Traumatismos da Medula Espinal/terapia , Transplante de Células-Tronco/métodos , Traumatismos em Atletas/terapia , Animais , Regeneração Nervosa/fisiologia , Sistema Nervoso Periférico/lesões
7.
eNeuro ; 11(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38871457

RESUMO

CRISPR/Cas9 gene editing represents an exciting avenue to study genes of unknown function and can be combined with genetically encoded tools such as fluorescent proteins, channelrhodopsins, DREADDs, and various biosensors to more deeply probe the function of these genes in different cell types. However, current strategies to also manipulate or visualize edited cells are challenging due to the large size of Cas9 proteins and the limited packaging capacity of adeno-associated viruses (AAVs). To overcome these constraints, we developed an alternative gene editing strategy using a single AAV vector and mouse lines that express Cre-dependent Cas9 to achieve efficient cell-type specific editing across the nervous system. Expressing Cre-dependent Cas9 from a genomic locus affords space to package guide RNAs for gene editing together with Cre-dependent, genetically encoded tools to manipulate, map, or monitor neurons using a single virus. We validated this strategy with three common tools in neuroscience: ChRonos, a channelrhodopsin, for studying synaptic transmission using optogenetics, GCaMP8f for recording Ca2+ transients using photometry, and mCherry for tracing axonal projections. We tested these tools in multiple brain regions and cell types, including GABAergic neurons in the nucleus accumbens, glutamatergic neurons projecting from the ventral pallidum to the lateral habenula, dopaminergic neurons in the ventral tegmental area, and proprioceptive neurons in the periphery. This flexible approach could help identify and test the function of novel genes affecting synaptic transmission, circuit activity, or morphology with a single viral injection.


Assuntos
Sistemas CRISPR-Cas , Dependovirus , Edição de Genes , Vetores Genéticos , Animais , Dependovirus/genética , Edição de Genes/métodos , Camundongos , Optogenética/métodos , Sistema Nervoso Central/metabolismo , Sistema Nervoso Periférico/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Feminino , Camundongos Transgênicos
8.
Acta Neuropathol Commun ; 12(1): 99, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886865

RESUMO

Filaments made of residues 120-254 of transmembrane protein 106B (TMEM106B) form in an age-dependent manner and can be extracted from the brains of neurologically normal individuals and those of subjects with a variety of neurodegenerative diseases. TMEM106B filament formation requires cleavage at residue 120 of the 274 amino acid protein; at present, it is not known if residues 255-274 form the fuzzy coat of TMEM106B filaments. Here we show that a second cleavage appears likely, based on staining with an antibody raised against residues 263-274 of TMEM106B. We also show that besides the brain TMEM106B inclusions form in dorsal root ganglia and spinal cord, where they were mostly found in non-neuronal cells. We confirm that in the brain, inclusions were most abundant in astrocytes. No inclusions were detected in heart, liver, spleen or hilar lymph nodes. Based on their staining with luminescent conjugated oligothiophenes, we confirm that TMEM106B inclusions are amyloids. By in situ immunoelectron microscopy, TMEM106B assemblies were often found in structures resembling endosomes and lysosomes.


Assuntos
Proteínas de Membrana , Proteínas do Tecido Nervoso , Proteínas de Membrana/metabolismo , Humanos , Proteínas do Tecido Nervoso/metabolismo , Medula Espinal/metabolismo , Amiloide/metabolismo , Gânglios Espinais/metabolismo , Encéfalo/metabolismo , Masculino , Feminino , Sistema Nervoso Periférico/metabolismo , Idoso , Animais
9.
Orphanet J Rare Dis ; 19(1): 217, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38790028

RESUMO

BACKGROUND: To investigate the peripheral nervous system involvement in S sialidosis with typical features of myoclonus, seizure, and giant waves in somatosensory evoked potentials suggesting hyperexcitability in the central nervous system. METHODS: The clinical presentation of patients with genetically confirmed sialidosis was recorded. Neurophysiological studies, including nerve conduction studies (NCSs), F-wave studies, and needle electromyography (EMG), were performed on these patients. RESULTS: Six patients (M/F: 2:4) were recruited. In addition to the classical presentation, intermittent painful paresthesia was noted in four patients, and three of whom reported it as the earliest symptom. In the NCSs, one patient had reduced compound muscle action potential amplitudes in the right ulnar nerve, while another patient had prolonged distal motor latency in the bilateral tibial and peroneal nerves. Prolonged F-wave latency (83.3%), repeater F-waves (50%), and neurogenic polyphasic waves in EMG (in 2 out of 3 examined patients) were also noted. Interestingly, a very late response was noted in the F-wave study of all patients, probably indicating lesions involving the proximal peripheral nerve or spinal cord. CONCLUSION: In addition to the central nervous system, the peripheral nervous system is also involved in sialidosis, with corresponding clinical symptoms. Further study on these phenomena is indicated.


Assuntos
Eletromiografia , Mucolipidoses , Humanos , Masculino , Feminino , Adulto , Mucolipidoses/fisiopatologia , Condução Nervosa/fisiologia , Adulto Jovem , Nervos Periféricos/fisiopatologia , Nervos Periféricos/patologia , Adolescente , Sistema Nervoso Periférico/fisiopatologia , Potenciais Somatossensoriais Evocados/fisiologia , Pessoa de Meia-Idade , Criança
11.
Biomolecules ; 14(5)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38785943

RESUMO

In the present study, we conducted a scoping review to provide an overview of the existing literature on the carbocyanine dye DiI, in human neuroanatomical tract tracing. The PubMed, Scopus, and Web of Science databases were systematically searched. We identified 61 studies published during the last three decades. While studies incorporated specimens across human life from the embryonic stage onwards, the majority of studies focused on adult human tissue. Studies that utilized peripheral nervous system (PNS) tissue were a minority, with the majority of studies focusing on the central nervous system (CNS). The most common topic of interest in previous tract tracing investigations was the connectivity of the visual pathway. DiI crystals were more commonly applied. Nevertheless, several studies utilized DiI in a paste or dissolved form. The maximum tracing distance and tracing speed achieved was, respectively, 70 mm and 1 mm/h. We identified studies that focused on optimizing tracing efficacy by varying parameters such as fixation, incubation temperature, dye re-application, or the application of electric fields. Additional studies aimed at broadening the scope of DiI use by assessing the utility of archival tissue and compatibility of tissue clearing in DiI applications. A combination of DiI tracing and immunohistochemistry in double-labeling studies have been shown to provide the means for assessing connectivity of phenotypically defined human CNS and PNS neuronal populations.


Assuntos
Técnicas de Rastreamento Neuroanatômico , Humanos , Técnicas de Rastreamento Neuroanatômico/métodos , Carbocianinas/química , Sistema Nervoso Central , Sistema Nervoso Periférico , Corantes Fluorescentes/química
12.
Exp Dermatol ; 33(5): e15104, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38794817

RESUMO

Psoriasis is a chronic systemic inflammatory cutaneous disease. Where the immune system plays an important role in its pathogenesis, with key inflammatory intercellular signalling peptides and proteins including IL-17 and IL-23. The psychoneurological system also figures prominently in development of psoriasis. There is a high prevalence of comorbidity between psoriasis and mental health disorders such as depression, anxiety and mania. Patients with psoriasis often suffer from pathological pain in the lesions, and their neurological accidents could improve the lesions in innervated areas. The immune system and the psychoneurological system interact closely in the pathogenesis of psoriasis. Patients with psoriasis exhibit abnormal levels of neuropeptides both in circulating and localized lesion, acting as immunomodulators involved in the inflammatory response. Moreover, receptors for inflammatory factors are expressed in both peripheral and central nervous systems (CNSs), suggesting that nervous system can receive and be influenced by signals from immune system. Key inflammatory intercellular signalling peptides and proteins in psoriasis, such as IL-17 and IL-23, can be involved in sensory signalling and may affect synaptic plasticity and the blood-brain barrier of CNS through the circulation. This review provides an overview of the multiple effects on the peripheral and CNS under conditions of systemic inflammation in psoriasis, providing a framework and inspiration for in-depth studies of neuroimmunomodulation in psoriasis.


Assuntos
Sistema Nervoso Central , Interleucina-17 , Interleucina-23 , Psoríase , Psoríase/metabolismo , Psoríase/imunologia , Humanos , Sistema Nervoso Central/metabolismo , Interleucina-23/metabolismo , Interleucina-17/metabolismo , Neuroimunomodulação , Neuropeptídeos/metabolismo , Inflamação/metabolismo , Sistema Nervoso Periférico/metabolismo , Animais , Transdução de Sinais
13.
Epigenetics Chromatin ; 17(1): 14, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715099

RESUMO

BACKGROUND: Prenatal nicotine exposure (PNE) has been documented to cause numerous deleterious effects on fetal development. However, the epigenetic changes promoted by nicotine exposure on germ cells are still not well understood. OBJECTIVES: In this study, we focused on elucidating the impact of prenatal nicotine exposure on regulatory epigenetic mechanisms important for germ cell development. METHODS: Sprague-Dawley rats were exposed to nicotine during pregnancy and male progeny was analyzed at 11 weeks of age. Testis morphology was analyzed using frozen testis sections and expression of germ cell markers was examined by RT-qPCR; histone modifications were assessed by Western Blot (WB). DNA methylation analysis was performed by methylation-specific PCR of bisulfite converted DNA. Genome-wide DNA methylation was analyzed using Methylated DNA immunoprecipitation (MeDIP)-seq. We also carried out transcriptomics analysis of pituitary glands by RNA-seq. RESULTS: We show that gestational exposure to nicotine reduces germ cell numbers, perturbs meiosis, affects the expression of germ line reprogramming responsive genes, and impacts the DNA methylation of nervous system genes in the testis. PNE also causes perturbation of gene expression in the pituitary gland of the brain. CONCLUSIONS: Our data demonstrate that PNE leads to perturbation of male spermatogenesis, and the observed effects are associated with changes of peripheral nervous system signaling pathways. Alterations in the expression of genes associated with diverse biological activities such as cell migration, cell adhesion and GABA signaling in the pituitary gland underscore the complexity of the effects of nicotine exposure during pregnancy.


Assuntos
Metilação de DNA , Epigênese Genética , Nicotina , Efeitos Tardios da Exposição Pré-Natal , Ratos Sprague-Dawley , Testículo , Animais , Masculino , Feminino , Gravidez , Ratos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Epigênese Genética/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Sistema Nervoso Periférico/efeitos dos fármacos , Sistema Nervoso Periférico/metabolismo
14.
Curr Biol ; 34(10): 2175-2185.e4, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38718797

RESUMO

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.


Assuntos
Sistema Nervoso Central , Sistema Nervoso Periférico , Animais , Sistema Nervoso Central/fisiologia , Sistema Nervoso Periférico/fisiologia , Comportamento Animal/fisiologia , Invertebrados/fisiologia
15.
Exp Neurol ; 377: 114783, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38688418

RESUMO

The structural and functional features of lymphatic vessels in the peripheral nervous system (pLVs) is still unclear. Here, we clarify the existence of pLVs in rats, PROX1-EGFP transgenic mice and human, and exhibit a clear three-dimensional structure for helping understand its structural features. Moreover, two specific phenotypes of lymphatics endothelial cells (Rnd1Hi LECs and Ccl21Hi LECs) in peripheral nerves are well characterized by single-cell sequencing. Subsequently, the ability of trans-lymphatic delivery to peripheral nerves via pLVs has been dynamically demonstrated. After peripheral nerve injury (PNI), extensive lymphangiogenesis occurs in the lesion area and further enhances the efficiency of retrograde lymphatic-nerve transport. In PNI animal models, subcutaneously footpad-injected exosomes are efficiently delivered to sciatic nerve via pLVs which can promote nerve regeneration. The trans-lymphatic delivery to peripheral nerves via pLVs can subtly bypass BNB which provides an easy and alternative delivery route for PNI treatment.


Assuntos
Vasos Linfáticos , Camundongos Transgênicos , Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Animais , Regeneração Nervosa/fisiologia , Vasos Linfáticos/fisiologia , Camundongos , Traumatismos dos Nervos Periféricos/patologia , Ratos , Humanos , Sistema Nervoso Periférico , Ratos Sprague-Dawley , Masculino , Nervo Isquiático/fisiologia , Nervo Isquiático/lesões , Linfangiogênese/fisiologia , Células Endoteliais/fisiologia , Exossomos/metabolismo
16.
BMC Biol ; 22(1): 74, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38561802

RESUMO

BACKGROUND: The tunicates form a group of filter-feeding marine animals closely related to vertebrates. They share with them a number of features such as a notochord and a dorsal neural tube in the tadpole larvae of ascidians, one of the three groups that make tunicates. However, a number of typical chordate characters have been lost in different branches of tunicates, a diverse and fast-evolving phylum. Consequently, the tunic, a sort of exoskeleton made of extracellular material including cellulose secreted by the epidermis, is the unifying character defining the tunicate phylum. In the larva of ascidians, the tunic differentiates in the tail into a median fin (with dorsal and ventral extended blades) and a caudal fin. RESULTS: Here we have performed experiments in the ascidian Phallusia mammillata to address the molecular control of tunic 3D morphogenesis. We have demonstrated that the tail epidermis medio-lateral patterning essential for peripheral nervous system specification also controls tunic elongation into fins. More specifically, when tail epidermis midline identity was abolished by BMP signaling inhibition, or CRISPR/Cas9 inactivation of the transcription factor coding genes Msx or Klf1/2/4/17, median fin did not form. We postulated that this genetic program should regulate effectors of tunic secretion. We thus analyzed the expression and regulation in different ascidian species of two genes acquired by horizontal gene transfer (HGT) from bacteria, CesA coding for a cellulose synthase and Gh6 coding for a cellulase. We have uncovered an unexpected dynamic history of these genes in tunicates and high levels of variability in gene expression and regulation among ascidians. Although, in Phallusia, Gh6 has a regionalized expression in the epidermis compatible with an involvement in fin elongation, our functional studies indicate a minor function during caudal fin formation only. CONCLUSIONS: Our study constitutes an important step in the study of the integration of HGT-acquired genes into developmental networks and a cellulose-based morphogenesis of extracellular material in animals.


Assuntos
Urocordados , Animais , Urocordados/genética , Morfogênese/genética , Epiderme , Sistema Nervoso Periférico , Larva/genética , Celulose
17.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612597

RESUMO

Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge to doctors and scientists. Injuries lead to neuroimmunological changes in the central nervous system (CNS), which may result in both secondary damage and the development of tactile and thermal hypersensitivity. In our review, based on the analysis of many experimental and clinical studies, we indicate that the mechanisms occurring both at the level of the brain after direct damage and at the level of the spinal cord after peripheral nerve damage have a common immunological basis. This suggests that there are opportunities for similar pharmacological therapeutic interventions in the damage of various etiologies. Experimental data indicate that after CNS/PNS damage, the levels of 16 among the 28 CC-family chemokines, i.e., CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL17, CCL19, CCL20, CCL21, and CCL22, increase in the brain and/or spinal cord and have strong proinflammatory and/or pronociceptive effects. According to the available literature data, further investigation is still needed for understanding the role of the remaining chemokines, especially six of them which were found in humans but not in mice/rats, i.e., CCL13, CCL14, CCL15, CCL16, CCL18, and CCL23. Over the past several years, the results of studies in which available pharmacological tools were used indicated that blocking individual receptors, e.g., CCR1 (J113863 and BX513), CCR2 (RS504393, CCX872, INCB3344, and AZ889), CCR3 (SB328437), CCR4 (C021 and AZD-2098), and CCR5 (maraviroc, AZD-5672, and TAK-220), has beneficial effects after damage to both the CNS and PNS. Recently, experimental data have proved that blockades exerted by double antagonists CCR1/3 (UCB 35625) and CCR2/5 (cenicriviroc) have very good anti-inflammatory and antinociceptive effects. In addition, both single (J113863, RS504393, SB328437, C021, and maraviroc) and dual (cenicriviroc) chemokine receptor antagonists enhanced the analgesic effect of opioid drugs. This review will display the evidence that a multidirectional strategy based on the modulation of neuronal-glial-immune interactions can significantly improve the health of patients after CNS and PNS damage by changing the activity of chemokines belonging to the CC family. Moreover, in the case of pain, the combined administration of such antagonists with opioid drugs could reduce therapeutic doses and minimize the risk of complications.


Assuntos
Analgésicos Opioides , Imidazóis , Naftalenos , Nitrocompostos , Sulfóxidos , Traumatismos do Sistema Nervoso , Humanos , Animais , Camundongos , Ratos , Maraviroc , Sistema Nervoso Central , Sistema Nervoso Periférico
18.
BMC Complement Med Ther ; 24(1): 117, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454382

RESUMO

A meditative 'technique' is conceived as a continuum of different affective states involving mind and body jointly. Meditative practices can involve cognitive effort (e.g., focused attention and open-minded techniques), as well as automatic and implicit practices (e.g., transcendental techniques). The NGALSO tantric self-healing meditation technique is a brief, comprehensive meditation technique relying on mind and body connection. In this study, we aimed to investigate the state and the trait neurophysiological correlates of NGALSO meditation practice. First, 19 EEG channels and a 3-lead ECG signal were recorded from 10 expert meditators (more than 7 years of daily meditation) and 10 healthy inexpert participants (controls) who underwent the same meditative procedure. The neuropsychological profiles of experts and controls were compared. Results showed that expert meditators had significantly higher power spectra on alpha, theta and beta, and a higher sympathetic tone with lower parasympathetic tone after meditation. Conversely, the control group had significantly less power spectra on alpha, theta and beta, and a higher parasympathetic tone with lower sympathetic tone after meditation. A machine learning approach also allowed us to classify experts vs. controls correctly by using only EEG Theta bands before or after meditation. ECG results allowed us to show a significantly higher effort by expert meditators vs. controls, thus suggesting that a higher effort is required for this meditation, in line with the principle 'no pain, no gain' in body and mind.


Assuntos
Meditação , Humanos , Sistema Nervoso Periférico
20.
Adv Drug Deliv Rev ; 208: 115275, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38442747

RESUMO

Ultrasound is a promising technology to address challenges in drug delivery, including limited drug penetration across physiological barriers and ineffective targeting. Here we provide an overview of the significant advances made in recent years in overcoming technical and pharmacological barriers using ultrasound-assisted drug delivery to the central and peripheral nervous system. We commence by exploring the fundamental principles of ultrasound physics and its interaction with tissue. The mechanisms of ultrasonic-enhanced drug delivery are examined, as well as the relevant tissue barriers. We highlight drug transport through such tissue barriers utilizing insonation alone, in combination with ultrasound contrast agents (e.g., microbubbles), and through innovative particulate drug delivery systems. Furthermore, we review advances in systems and devices for providing therapeutic ultrasound, as their practicality and accessibility are crucial for clinical application.


Assuntos
Sistemas de Liberação de Medicamentos , Terapia por Ultrassom , Humanos , Ultrassonografia , Sistema Nervoso Periférico , Microbolhas
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