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1.
Arch Esp Urol ; 74(7): 715-719, 2021 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-34472442

RESUMO

We present two different cases of involvement of the nervous system due to prostate cancer. We know that atypical metastases can also affect supraclavicular lymphatics, adrenal gland and testicles. In these cases we present a typical places in the nervous system. We musttake into account that sometimes the shape the presentation of symptoms can be confused with other pathologies. In some cases, this type of patient has never had a urological check-up and in our sagacity as doctors we come to find the origin of the problem: the prostate.


Assuntos
Neoplasias da Próstata , Humanos , Masculino , Sistema Nervoso
2.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34576153

RESUMO

The endocannabinoid system plays a central role in the earliest stages of embryonic, postnatal and adolescent neurodevelopment. Aberrant activity of this system at key developmental phases has been shown to affect neural development. The aim of this review is to synthesise and analyse preclinical insights within rodent populations, focusing on the effects that perinatal (embryonic, gestational and early postnatal developmental stages) and adolescent (postnatal day 21-60) cannabinoid exposure impose across time on the subsequent activity of various drugs of abuse. Results in rodents show that exposure to cannabinoids during the perinatal and adolescent period can lead to multifaceted behavioural and molecular changes. In the perinatal period, significant effects of Δ9-THC exposure on subsequent opiate and amphetamine reward-related behaviours were observed primarily in male rodents. These effects were not extended to include cocaine or alcohol. In adolescence, various cannabinoid agonists were used experimentally. This array of cannabinoids demonstrated consistent effects on opioids across sex. In contrast, no significant effects were observed regarding the future activity of amphetamines and cocaine. However, these studies focused primarily on male rodents. In conclusion, numerous gaps and limitations are apparent in the current body of research. The sparsity of studies analysing the perinatal period must be addressed. Future research within both periods must also focus on delineating sex-specific effects, moving away from a male-centric focus. Studies should also aim to utilise more clinically relevant cannabinoid treatments.


Assuntos
Canabinoides/farmacologia , Drogas Ilícitas/efeitos adversos , Sistema Nervoso/embriologia , Animais , Comportamento , Humanos , Sistema Nervoso/efeitos dos fármacos
5.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445623

RESUMO

Human breast milk lipids have major beneficial effects: they promote infant early brain development, growth and health. To identify the relationship between human breast milk lipids and infant neurodevelopment, multivariate analyses that combined lipidomics and psychological Bayley-III scales evaluation were utilized. We identified that 9,12-octadecadiynoic acid has a significantly positive correlation with infant adaptive behavioral development, which is a crucial neurodevelopment to manage risk from environmental stress. To further clarify the biological function of 9,12-octadecadiynoic acid in regulating neurodevelopment, Caenorhabditis elegans (C. elegans) was used as a model to investigate the effect of 9,12-octadecadiynoic acid on neurobehavioral development. Supplementation with 9,12-octadecadiynoic acid from the L1 to L4 stage in larvae affected locomotive behaviors and foraging ability that were not socially interactive, implying that 9,12-octadecadiynoic acid is involved in regulating the serotonergic neuronal ability. We found that supplementary 0.1 µM 9,12-octadecadiynoic acid accelerated the locomotive ability and foraging ability via increasing the expression of serotonin transporter mod-1. Antioxidant defense genes, sod-1, sod-3 and cyp-35A2 are involved in 9,12-octadecadiynoic acid-induced motor neuronal activity. Nevertheless, supplementary 9,12-octadecadiynoic acid at concentrations above 1 µM significantly attenuated locomotive behaviors, foraging ability, serotonin synthesis, serotonin-related gene expressions and stress-related gene expression, resulting in the decreased longevity of worms in the experiment. In conclusion, our study demonstrates the biological function of 9,12-octadecadiynoic acid in governing adaptive behavioral development.


Assuntos
Comportamento Animal/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Larva/efeitos dos fármacos , Ácido Linoleico/farmacologia , Sistema Nervoso/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Larva/crescimento & desenvolvimento , Sistema Nervoso/crescimento & desenvolvimento
6.
J Enzyme Inhib Med Chem ; 36(1): 1860-1873, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34425715

RESUMO

To discover novel scaffolds as leads against dementia, a series of δ-aryl-1,3-dienesulfonyl fluorides with α-halo, α-aryl and α-alkynyl were assayed for ChE inhibitory activity, in which compound A10 was identified as a selective BuChE inhibitor (IC50 = 0.021 µM for eqBChE, 3.62 µM for hBuChE). SAR of BuChE inhibition showed: (i) o- > m- > p-; -OCH3 > -CH3 > -Cl (-Br) for δ-aryl; (ii) α-Br > α-Cl, α-I. Compound A10 exhibited neuroprotective, BBB penetration, mixed competitive inhibitory effect on BuChE (Ki = 29 nM), and benign neural and hepatic safety. Treatment with A10 could almost entirely recover the Aß1-42-induced cognitive dysfunction to the normal level, and the assessment of total amount of Aß1-42 confirmed its anti-amyloidogenic profile. Therefore, the potential BuChE inhibitor A10 is a promising effective lead for the treatment of AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/química , Colinesterases/metabolismo , Fármacos Neuroprotetores/química , Ácidos Sulfínicos/química , Alcinos/química , Amiloide/metabolismo , Animais , Comportamento Animal , Barreira Hematoencefálica/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Desenho de Fármacos , Humanos , Fígado , Masculino , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Estrutura Molecular , Teste do Labirinto Aquático de Morris , Sistema Nervoso , Fármacos Neuroprotetores/farmacologia , Relação Estrutura-Atividade , Ácidos Sulfínicos/farmacologia
7.
Biomolecules ; 11(8)2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34439878

RESUMO

The study is dedicated to the investigation of serotonin (5-hydroxytryptamine, 5-HT) and 5-HT7 type serotonin receptor of localisation in larvae of two parasitic flatworms Opisthorchis felineus (Rivolta, 1884) Blanchard, 1895 and Hymenolepis diminuta Rudolphi, 1819, performed using the immunocytochemical method and confocal laser scanning microscopy (CLSM). Using whole mount preparations and specific antibodies, a microscopic analysis of the spatial distribution of 5-HT7-immunoreactivity(-IR) was revealed in worm tissue. In metacercariae of O. felineus 5-HT7-IR was observed in the main nerve cords and in the head commissure connecting the head ganglia. The presence of 5-HT7-IR was also found in several structures located on the oral sucker. 5-HT7-IR was evident in the round glandular cells scattered throughout the larva body. In cysticercoids of H. diminuta immunostaining to 5-HT7 was found in flame cells of the excretory system. Weak staining to 5-HT7 was observed along the longitudinal and transverse muscle fibres comprising the body wall and musculature of suckers, in thin longitudinal nerve cords and a connective commissure of the central nervous system. Available publications on serotonin action in flatworms and serotonin receptors identification were reviewed. Own results and the published data indicate that the muscular structures of flatworms are deeply supplied by 5-HT7-IR elements. It suggests that the 5-HT7 type receptor can mediate the serotonin action in the investigated species and is an important component of the flatworm motor control system. The study of the neurochemical basis of parasitic flatworms can play an important role in the solution of fundamental problems in early development of the nervous system and the evolution of neuronal signalling components.


Assuntos
Hymenolepis diminuta/imunologia , Opisthorchis/imunologia , Receptores de Serotonina/imunologia , Serotonina/metabolismo , Animais , Sistema Nervoso/metabolismo
8.
ACS Biomater Sci Eng ; 7(8): 3503-3529, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34291638

RESUMO

The complexity of the nervous system structure and function, and its slow regeneration rate, makes it more difficult to treat compared to other tissues in the human body when an injury occurs. Moreover, the current therapeutic approaches including the use of autografts, allografts, and pharmacological agents have several drawbacks and can not fully restore nervous system injuries. Recently, nanotechnology and tissue engineering approaches have attracted many researchers to guide tissue regeneration in an effective manner. Owing to their remarkable physicochemical and biological properties, two-dimensional (2D) nanomaterials have been extensively studied in the tissue engineering and regenerative medicine field. The great conductivity of these materials makes them a promising candidate for the development of novel scaffolds for neural tissue engineering application. Moreover, the high loading capacity of 2D nanomaterials also has attracted many researchers to utilize them as a drug/gene delivery method to treat various devastating nervous system disorders. This review will first introduce the fundamental physicochemical properties of 2D nanomaterials used in biomedicine and the supporting biological properties of 2D nanomaterials for inducing neuroregeneration, including their biocompatibility on neural cells, the ability to promote the neural differentiation of stem cells, and their immunomodulatory properties which are beneficial for alleviating chronic inflammation at the site of the nervous system injury. It also discusses various types of 2D nanomaterials-based scaffolds for neural tissue engineering applications. Then, the latest progress on the use of 2D nanomaterials for nervous system disorder treatment is summarized. Finally, a discussion of the challenges and prospects of 2D nanomaterials-based applications in neural tissue engineering is provided.


Assuntos
Nanoestruturas , Engenharia Tecidual , Humanos , Nanotecnologia , Sistema Nervoso , Medicina Regenerativa
9.
Cell Physiol Biochem ; 55(S2): 71-88, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34242500

RESUMO

Psychological stress is an important factor involved in disease manifestations of human papillomavirus (HPV) infection, and it can participate in HPV-associated carcinogenesis. The impact or effect which stress can have (exert) depends on a person's genetic pool, experiences and behaviors. Due to inconsistencies in some study results, this issue remains a subject of research. Concerning the course of HPV manifestations, it has been observed that a higher number of life stressors in at least the previous 6 months, the absence of social support and the types of personal coping mechanisms employed, all influence HPV progression. In women with cervical dysplasia, a connection between greater stress experiences and dysregulation of specific immune responses has been observed. Once HPV enters a cell via the α6 integrin there are three possible sequences: latent infection, subclinical infection, and clinically manifest disease. HPV proliferation in differentiated epithelial cells induces morphologically cytopathic changes (koilocytosis, epidermal thickening, hyperplasia, hyperkeratosis). Oncogenic transformation requires the integration of the virus genome into the host genome. In doing so, DNA in the E1 region of E2 breaks down, leading to transcription disorders of E6 and E7. For the formation of irreversible malignancy, the following sequence is necessary: initial expression of E6 and E7 genes followed by suppression of apoptosis and the stabile expression of E6 and E7 proteins that protect transformed cells from apoptosis. A successful immune response is characterized by a strong, local cell-mediated immune response. Several factors are important for the regression of HPV manifestation/infection, among which is psychological stress which can prolong the duration and severity of HPV disease. Stress hormones may reactivate latent tumor viruses, stimulate viral oncogene expression, and inhibit antiviral host responses. In the regression of HPV infection, increased activity of Th1 cells was observed. However, during psychosocial stress, a decrease in the Th1 type of immune response is seen, and there is a shift towards a Th2 response. Understanding perceived stress and biological changes in stress, as well as the evaluation of immune parameters, gives researchers a better picture of how stress influences HPV infections and how to improve disease management and outcomes.


Assuntos
Papillomaviridae/fisiologia , Infecções por Papillomavirus/psicologia , Estresse Psicológico , Carcinogênese , DNA Viral/genética , DNA Viral/metabolismo , Células Epiteliais/citologia , Células Epiteliais/virologia , Humanos , Sistema Nervoso/metabolismo , Sistema Nervoso/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/patologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/virologia
10.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34210012

RESUMO

Cancer is one of the most common causes of death worldwide. Along with the advances in diagnostic technology achieved through industry-academia partnerships, the survival rate of cancer patients has improved dramatically through treatments that include surgery, radiation therapy, and pharmacotherapy. This has increased the population of cancer "survivors" and made cancer survivorship an important part of life for patients. The senses of taste and smell during swallowing and cachexia play important roles in dysphagia associated with nutritional disorders in cancer patients. Cancerous lesions in the brain can cause dysphagia. Taste and smell disorders that contribute to swallowing can worsen or develop because of pharmacotherapy or radiation therapy; metabolic or central nervous system damage due to cachexia, sarcopenia, or inflammation can also cause dysphagia. As the causes of eating disorders in cancer patients are complex and involve multiple factors, cancer patients require a multifaceted and long-term approach by the medical care team.


Assuntos
Neoplasias Encefálicas/complicações , Transtornos de Deglutição/metabolismo , Sistema Nervoso/metabolismo , Neoplasias Encefálicas/metabolismo , Transtornos de Deglutição/etiologia , Humanos , Olfato , Paladar
11.
eNeuro ; 8(4)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34244311

RESUMO

Highlighted Research Paper: Lewis AS, Calipari ES, Siciliano CA (2021) Toward Standardized Guidelines for Investigating Neural Circuit Control of Behavior in Animal Research.


Assuntos
Comportamento Animal , Sistema Nervoso , Animais
12.
Trends Neurosci ; 44(9): 753-764, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34303552

RESUMO

Malnutrition refers to a dearth, excess, or altered differential ratios of calories, macronutrients, or micronutrients. Malnutrition, particularly during early life, is a pressing global health and socioeconomic burden that is increasingly associated with neurodevelopmental impairments. Understanding how perinatal malnutrition influences brain development is crucial to uncovering fundamental mechanisms for establishing behavioral neurocircuits, with the potential to inform public policy and clinical interventions for neurodevelopmental conditions. Recent studies reveal that the gut microbiome can mediate dietary effects on host physiology and that the microbiome modulates the development and function of the nervous system. This review discusses evidence that perinatal malnutrition alters brain development and examines the maternal and neonatal microbiome as a potential contributing factor.


Assuntos
Microbioma Gastrointestinal , Desnutrição , Microbiota , Dieta , Feminino , Humanos , Recém-Nascido , Sistema Nervoso , Gravidez
13.
Cell Mol Life Sci ; 78(16): 6033-6049, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34274976

RESUMO

Melanocytes are pigmented cells residing mostly in the skin and hair follicles of vertebrates, where they contribute to colouration and protection against UV-B radiation. However, the spectrum of their functions reaches far beyond that. For instance, these pigment-producing cells are found inside the inner ear, where they contribute to the hearing function, and in the heart, where they are involved in the electrical conductivity and support the stiffness of cardiac valves. The embryonic origin of such extracutaneous melanocytes is not clear. We took advantage of lineage-tracing experiments combined with 3D visualizations and gene knockout strategies to address this long-standing question. We revealed that Schwann cell precursors are recruited from the local innervation during embryonic development and give rise to extracutaneous melanocytes in the heart, brain meninges, inner ear, and other locations. In embryos with a knockout of the EdnrB receptor, a condition imitating Waardenburg syndrome, we observed only nerve-associated melanoblasts, which failed to detach from the nerves and to enter the inner ear. Finally, we looked into the evolutionary aspects of extracutaneous melanocytes and found that pigment cells are associated mainly with nerves and blood vessels in amphibians and fish. This new knowledge of the nerve-dependent origin of extracutaneous pigment cells might be directly relevant to the formation of extracutaneous melanoma in humans.


Assuntos
Encéfalo/fisiologia , Orelha Interna/fisiologia , Coração/fisiologia , Meninges/fisiologia , Sistema Nervoso/fisiopatologia , Células de Schwann/fisiologia , Anfíbios/metabolismo , Anfíbios/fisiologia , Animais , Encéfalo/metabolismo , Linhagem da Célula/fisiologia , Orelha Interna/metabolismo , Desenvolvimento Embrionário/fisiologia , Feminino , Peixes/metabolismo , Peixes/fisiologia , Melanócitos/metabolismo , Melanócitos/fisiologia , Meninges/metabolismo , Camundongos , Sistema Nervoso/metabolismo , Gravidez , Receptor de Endotelina B/metabolismo , Células de Schwann/metabolismo
14.
Elife ; 102021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34328079

RESUMO

Hydra vulgaris is an emerging model organism for neuroscience due to its small size, transparency, genetic tractability, and regenerative nervous system; however, fundamental properties of its sensorimotor behaviors remain unknown. Here, we use microfluidic devices combined with fluorescent calcium imaging and surgical resectioning to study how the diffuse nervous system coordinates Hydra's mechanosensory response. Mechanical stimuli cause animals to contract, and we find this response relies on at least two distinct networks of neurons in the oral and aboral regions of the animal. Different activity patterns arise in these networks depending on whether the animal is contracting spontaneously or contracting in response to mechanical stimulation. Together, these findings improve our understanding of how Hydra's diffuse nervous system coordinates sensorimotor behaviors. These insights help reveal how sensory information is processed in an animal with a diffuse, radially symmetric neural architecture unlike the dense, bilaterally symmetric nervous systems found in most model organisms.


Assuntos
Hydra/fisiologia , Mecanotransdução Celular/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Animais , Cálcio/metabolismo , Técnicas Analíticas Microfluídicas , Sistema Nervoso/metabolismo , Imagem Óptica
15.
Sci Transl Med ; 13(598)2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135112

RESUMO

More than 50% of the world population is chronically infected with herpesviruses. Herpes simplex virus (HSV) infections are the cause of herpes labialis (cold sores), genital herpes, and sight-impairing keratitis. Less frequently, life-threatening disseminated disease (encephalitis and generalized viremia) can also occur, mainly in immunocompromised patients and newborns. After primary infection, HSV persists for life in a latent state in trigeminal or sacral ganglia and, triggered by diverse stimuli, disease recurs in more than 30% of patients up to several times a year. Current therapy with nucleoside analogs targeting the viral polymerase is somewhat effective but limited by poor exposure in the nervous system, and latent infections are not affected by therapy. Here, we report on an inhibitor of HSV helicase-primase with potent in vitro anti-herpes activity, a different mechanism of action, a low frequency of HSV resistance, and a favorable pharmacokinetic and safety profile. Improved target tissue exposure results in superior efficacy in preventing and treating HSV infection and disease in animal models as compared to standard of care. Therapy of primary HSV infections with drug candidate IM-250 {(S)-2-(2',5'-difluoro-[1,1'-biphenyl]-4-yl)-N-methyl-N-(4-methyl-5-(S-methylsulfon-imidoyl)thiazol-2-yl)acetamide} not only reduces the duration of disease symptoms or time to healing but also prevents recurrent disease in guinea pigs. Treatment of recurrent infections reduces the frequency of recurrences and viral shedding, and, unlike nucleosidic drugs, IM-250 remains effective for a time after cessation of treatment. Hence, IM-250 has advantages over standard-of-care therapies and represents a promising therapeutic for chronic HSV infection, including nucleoside-resistant HSV.


Assuntos
Antivirais , Herpes Simples , Latência Viral/efeitos dos fármacos , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , DNA Primase , Cobaias , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 2 , Humanos , Sistema Nervoso
16.
Crit Rev Toxicol ; 51(4): 328-358, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34074207

RESUMO

The current understanding of thyroid-related adverse outcome pathways (AOPs) with adverse neurodevelopmental outcomes in mammals has been reviewed. This served to establish if standard rodent toxicity test methods and in vitro assays allow identifying thyroid-related modes-of-action potentially leading to adverse neurodevelopmental outcomes, and the human relevance of effects - in line with the European Commission's Endocrine Disruptor Criteria. The underlying hypothesis is that an understanding of the key events of relevant AOPs provides insight into differences in incidence, magnitude, or species sensitivity of adverse outcomes. The rodent studies include measurements of serum thyroid hormones, thyroid gland pathology and neurodevelopmental assessments, but do not directly inform on specific modes-of-action. Opportunities to address additional non-routine parameters reflecting critical events of AOPs in toxicological assessments are presented. These parameters appear relevant to support the identification of specific thyroid-related modes-of-action, provided that prevailing technical limitations are overcome. Current understanding of quantitative key event relationships is often weak, but would be needed to determine if the triggering of a molecular initiating event will ultimately result in an adverse outcome. Also, significant species differences in all processes related to thyroid hormone signalling are evident, but the biological implications thereof (including human relevance) are often unknown. In conclusion, careful consideration of the measurement (e.g. timing, method) and interpretation of additional non-routine parameters is warranted. These findings will be used in a subsequent paper to propose a testing strategy to identify if a substance may elicit maternal thyroid hormone imbalance and potentially also neurodevelopmental effects in the progeny.


Assuntos
Testes de Toxicidade/métodos , Rotas de Resultados Adversos , Animais , Disruptores Endócrinos , Humanos , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/crescimento & desenvolvimento , Síndromes Neurotóxicas , Medição de Risco , Glândula Tireoide , Hormônios Tireóideos
17.
Trends Mol Med ; 27(9): 895-906, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34175230

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause chronic and acute disease. Postacute sequelae of SARS-CoV-2 infection (PASC) include injury to the lungs, heart, kidneys, and brain that may produce a variety of symptoms. PASC also includes a post-coronavirus disease 2019 (COVID-19) syndrome ('long COVID') with features that can follow other acute infectious diseases and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here we summarize what is known about the pathogenesis of ME/CFS and of 'acute' COVID-19, and we speculate that the pathogenesis of post-COVID-19 syndrome in some people may be similar to that of ME/CFS. We propose molecular mechanisms that might explain the fatigue and related symptoms in both illnesses, and we suggest a research agenda for both ME/CFS and post-COVID-19 syndrome.


Assuntos
COVID-19/complicações , Síndrome de Fadiga Crônica/etiologia , COVID-19/etiologia , COVID-19/fisiopatologia , Metabolismo Energético , Síndrome de Fadiga Crônica/fisiopatologia , Microbioma Gastrointestinal , Humanos , Sistema Nervoso/fisiopatologia
18.
Arq Neuropsiquiatr ; 79(4): 346-349, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34133516

RESUMO

The longstanding study of gross anatomy experienced a considerable improvement with the advent of the microscope in the early 17th century. The representative personality of this new era certainly was Marcello Malpighi, seen as "founder of microscopic anatomy". He studied, with a rudimentary compound microscope, numerous tissues and organs of several classes of animals, as well as plants. He described, for the first time, the microscopic structure of the nervous system, identifying in the gray matter of its various levels minute elements he took as "glands". It should be reminded that the concept of "cell" (and "nerve cell") was unknown at his time. Many researchers followed, performing microscopic studies, but without better results, and Malpighi's view was maintained until the beginning of the 19th century, when new histological processing and staining techniques appeared, as well as improved microscopes.


Assuntos
Sistema Nervoso , Neurônios , Animais , Córtex Cerebral , Substância Cinzenta , História do Século XVII , Itália , Coloração e Rotulagem
19.
Elife ; 102021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34165430

RESUMO

The generation of the enormous diversity of neuronal cell types in a differentiating nervous system entails the activation of neuron type-specific gene batteries. To examine the regulatory logic that controls the expression of neuron type-specific gene batteries, we interrogate single cell expression profiles of all 118 neuron classes of the Caenorhabditis elegans nervous system for the presence of DNA binding motifs of 136 neuronally expressed C. elegans transcription factors. Using a phylogenetic footprinting pipeline, we identify cis-regulatory motif enrichments among neuron class-specific gene batteries and we identify cognate transcription factors for 117 of the 118 neuron classes. In addition to predicting novel regulators of neuronal identities, our nervous system-wide analysis at single cell resolution supports the hypothesis that many transcription factors directly co-regulate the cohort of effector genes that define a neuron type, thereby corroborating the concept of so-called terminal selectors of neuronal identity. Our analysis provides a blueprint for how individual components of an entire nervous system are genetically specified.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Diferenciação Celular , Regulação da Expressão Gênica no Desenvolvimento , Neurônios/fisiologia , Fatores de Transcrição/genética , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Simulação por Computador , Sistema Nervoso/crescimento & desenvolvimento , Fatores de Transcrição/metabolismo
20.
J Cell Biol ; 220(7)2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34152362

RESUMO

Lipid droplets are dynamic intracellular lipid storage organelles that respond to the physiological state of cells. In addition to controlling cell metabolism, they play a protective role for many cellular stressors, including oxidative stress. Despite prior descriptions of lipid droplets appearing in the brain as early as a century ago, only recently has the role of lipid droplets in cells found in the brain begun to be understood. Lipid droplet functions have now been described for cells of the nervous system in the context of development, aging, and an increasing number of neuropathologies. Here, we review the basic mechanisms of lipid droplet formation, turnover, and function and discuss how these mechanisms enable lipid droplets to function in different cell types of the nervous system under healthy and pathological conditions.


Assuntos
Envelhecimento/genética , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/genética , Sistema Nervoso/metabolismo , Envelhecimento/metabolismo , Animais , Humanos , Estresse Oxidativo/genética
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