RESUMO
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by resting tremor, bradykinesia, rigidity, and postural instability that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) is the primary neurotransmitter involved in this disease, but cholinergic imbalance has also been implicated. Current intervention in PD is focused on replenishing central DA, which provides remarkable temporary symptomatic relief but does not address neuronal loss and the progression of the disease. It has been well established that neuronal nicotinic cholinergic receptors (nAChRs) can regulate DA release and that nicotine itself may have neuroprotective effects. Recent studies identified nAChRs in nonneuronal cell types, including glial cells, where they may regulate inflammatory responses. Given the crucial role of neuroinflammation in dopaminergic degeneration and the involvement of microglia and astrocytes in this response, glial nAChRs may provide a novel therapeutic target in the prevention and/or treatment of PD. In this review, following a brief discussion of PD, we focus on the role of glial cells and, specifically, their nAChRs in PD pathology and/or treatment.
Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Receptores Nicotínicos , Humanos , Doença de Parkinson/metabolismo , Receptores Nicotínicos/metabolismo , Doenças Neurodegenerativas/metabolismo , Nicotina/metabolismo , Dopamina/metabolismo , Astrócitos/metabolismoRESUMO
The Wi-SUN FAN (Wireless Smart Ubiquitous Network Field Area Network) standard is attracting great interest in various applications such as smart meters, smart cities and Internet of Things (IoT) devices due to the attractive features that the standard offers, such as multihop and mesh topologies, a relatively high data rate, frequency hopping, and interoperability between manufacturers. However, the process of connecting nodes in Wi-SUN FAN networks, which includes discovering, joining, and forming the network, has been shown to be slow, especially in multihop environments, which has motivated research and experimentation to analyze this process. In the existing literature, to measure network formation time, some authors have performed experiments with up to 100 devices, which is a costly and time-consuming methodology. Others have used simulation tools that are difficult to replicate, because little information is available about the methodology used or because they are proprietary. Despite these efforts, there is still a lack of information to adequately assess the formation time of Wi-SUN FAN networks, since the experimental tests reported in the literature are expensive and time-consuming. Therefore, alternatives such as computer simulation have been explored to speed up performance analysis in different scenarios. With this perspective, this paper is focused on the implementation of the Wi-SUN FAN network formation process using the Contiki-NG open source operating system and the Cooja simultor, where a functionality was added that makes it possible to efficiently analyze the network performance, thereby facilitating the implementation of new techniques to reduce network training time. The simulation tool was integrated into Contiki-NG and has been used to estimate the network formation times in various indoor environments. The correspondence between the experimental and numerical results obtained shows that our proposal is efficient to study the formation process of this type of networks.
RESUMO
SUMMARY STATEMENT: NG2-glia alters its dynamics in response to L-DOPA-induced dyskinesia. In these animals, striatal NG2-glia density was reduced with cells presenting activated phenotype while doxycycline antidyskinetic therapy promotes a return to NG2-glia cell density and protein to a not activated state.
Assuntos
Discinesia Induzida por Medicamentos , Transtornos Parkinsonianos , Ratos , Animais , Levodopa/efeitos adversos , Antiparkinsonianos/efeitos adversos , Doxiciclina/uso terapêutico , Ratos Sprague-Dawley , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/induzido quimicamente , Discinesia Induzida por Medicamentos/tratamento farmacológico , Neuroglia/metabolismo , Oxidopamina , Modelos Animais de DoençasRESUMO
The identification of carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa is important for treating and controlling hospital infections. The recommended methods for their identification require a long waiting time, technical training, and expertise. Lateral flow immunoassays such as NG-Test CARBA 5® overcome these needs. We analyzed 84 clinical isolates of carbapenem-resistant Enterobacterales and P. aeruginosa from four different hospitals in a two-year period. Antimicrobial resistance patterns were confirmed with the broth dilution method. Evaluation of KPC, VIM, NDM, IMP, and OXA-48-like enzymes was performed and compared to NG-Test CARBA 5 and phenotypic assays. Enterobacterales represented 69% of isolates and P. aeruginosa represented 31%. Carbapenemase-producing strains were 51 (88%) of Enterobacterales and 23 (88.4%) of P. aeruginosa; 20 (34%) and 23 (88%) were Class B ß-lactamases, respectively. The NG-Test CARBA 5® assay for Enterobacterales showed high sensitivity (98%), specificity (100%), and PPV (100%); however, it did not for P. aeruginosa. The Kappa concordance coefficient was 0.92 for Enterobacterales and 0.52 for P. aeruginosa. NG-Test CARBA 5® is a fast and easy-to-use assay. In Enterobacterales, we found excellent agreement in our comparison with molecular tests. Despite the low agreement in P. aeruginosa, we suggest that this test could be used as a complementary tool.
RESUMO
The aqueduct of Sylvius connects the third with the fourth ventricle and is surrounded by the Periaqueductal Grey. Here, we report a novel niche of cells in the dorsal section of the aqueduct, hereby named dorsal aqueduct niche or DAN, by applying a battery of selective markers and transgenic mouse lines. The somata of DAN cells are located toward the lumen of the ventricle forming multiple layers in close association with the cerebrospinal fluid (CSF). A single process emerges from the soma and run with the blood vessels. Cells of the DAN express radial glia/stem cell markers such as GFAP, vimentin and nestin, and the glutamate transporter GLAST or the oligodendrocyte precursor/pericyte marker NG2, thereby suggesting their potential for the generation of new cells. Morphologically, DAN cells resemble tanycytes of the third ventricle, which transfer biochemical signals from the CSF to the central nervous system and display proliferative capacity. The aqueduct ependymal lining can proliferate as observed by the integration of BrdU and expression of Ki67. Thus, the dorsal section of the aqueduct of Sylvius possesses cells that may act a niche of new glial cells in the adult mouse brain.
Assuntos
Aqueduto do Mesencéfalo , Terceiro Ventrículo , Animais , Camundongos , Aqueduto do Mesencéfalo/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Terceiro Ventrículo/metabolismo , Neuroglia/metabolismo , Epêndima/metabolismo , Camundongos TransgênicosRESUMO
ABSTRACT Objective: We hypothesized that perinatal manipulations of the nitrergic system would affect adult animal behaviors. Methods: We tested this hypothesis by perinatally administering N(G)-Nitro-L-arginine methyl ester (L-NAME), a non-specific antagonist of nitric oxide synthase for 15 days and assessed anxiety- and depression-like behaviors in adult mice. At 70 days of age, the mice were subjected to a battery of tests consisting of the open-field, light/dark box, forced swim, and tail-flick tests. The tests were performed at two-day intervals, and the order of the tests within the battery was determined according to the progressive invasiveness degree. Results: L-NAME-treated animals exhibited decreased anxiety-like behavior in the light/dark box and open field tests, with no change in locomotor activity. Additionally, they demonstrated decreased depression-like behavior in the forced swim test and no change in pain perception in the tail-flick test. Conclusion: The nitrergic system is possibly involved in neural circuitry development that regulates behaviors since blocking perinatal nitric oxide production decreases anxiety- and depression-like behaviors in adult mice.
RESUMO
Ghrelin is a stomach-derived peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) and displays a plethora of neuroendocrine, metabolic, autonomic and behavioral actions. It has been proposed that some actions of ghrelin are exerted via the vagus nerve, which provides a bidirectional communication between the central nervous system and peripheral systems. The vagus nerve comprises sensory fibers, which originate from neurons of the nodose and jugular ganglia, and motor fibers, which originate from neurons of the medulla. Many anatomical studies have mapped GHSR expression in vagal sensory or motor neurons. Also, numerous functional studies investigated the role of the vagus nerve mediating specific actions of ghrelin. Here, we critically review the topic and discuss the available evidence supporting, or not, a role for the vagus nerve mediating some specific actions of ghrelin. We conclude that studies using rats have provided the most congruent evidence indicating that the vagus nerve mediates some actions of ghrelin on the digestive and cardiovascular systems, whereas studies in mice resulted in conflicting observations. Even considering exclusively studies performed in rats, the putative role of the vagus nerve in mediating the orexigenic and growth hormone (GH) secretagogue properties of ghrelin remains debated. In humans, studies are still insufficient to draw definitive conclusions regarding the role of the vagus nerve mediating most of the actions of ghrelin. Thus, the extent to which the vagus nerve mediates ghrelin actions, particularly in humans, is still uncertain and likely one of the most intriguing unsolved aspects of the field.
RESUMO
Oligodendrocytes (OLs) produce myelin to insulate axons. This accelerates action potential propagation, allowing nerve impulse information to synchronize within complex neuronal ensembles and promoting brain connectivity. Brain plasticity includes myelination, a process that starts early after birth and continues throughout life. Myelin repair, followed by injury or disease, requires new OLs differentiated from a population derived from oligodendrocyte precursor cells (OPCs) that continue to proliferate, migrate and differentiate to preserve and remodel myelin in the adult central nervous system. OPCs represent the largest proliferative neural cell population outside the adult neurogenic niches in the brain. OPCs receive synaptic inputs from glutamatergic and GABAergic neurons throughout neurodevelopment, a unique feature among glial cells. Neuron-glia communication through GABA signaling in OPCs has been shown to play a role in myelin plasticity and repair. In this review we will focus on the molecular and functional properties of GABA A receptors (GABA A Rs) expressed by OPCs and their potential role in remyelination.
RESUMO
The hilus plays an important role modulating the excitability of the hippocampal dentate gyrus (DG). It also harbors proliferative cells whose proliferation rate is modified during pathological events. However, the characterization of these cells, in terms of cellular identity, lineage, and fate, as well as the morphology and proportion of each cell subpopulation has been poorly studied. Therefore, a deeper investigation of hilar proliferative cells might expand the knowledge not only in the physiology, but in the pathophysiological processes related to the hippocampus too. The aim of this work was to perform an integrative study characterizing the identity of proliferative cells populations harbored in the hilus, along with morphology and proportion. In addition, this study provides comparative evidence of the subgranular zone (SGZ) of the DG. Quantified cells included proliferative, neural precursor, Type 1, oligodendrocyte progenitor (OPCs), neural progenitor (NPCs), and proliferative mature astrocytes in the hilus and SGZ of Wistar adult rats. Our results showed that 84% of the hilar proliferative cells correspond to neural precursor cells, OPCs and NPCs being the most abundant at 54 and 45%, respectively, unlike the SGZ, where OPCs represent only 11%. Proliferative mature astrocytes and Type 1-like cells were rarely observed in the hilus. Together, our results lay the basis for future studies focused on the lineage and fate of hilar proliferative cells and suggest that the hilus could be relevant to the formation of new cells that modulate multiple physiological processes governed by the hippocampus.
Assuntos
Proliferação de Células/fisiologia , Giro Denteado/fisiologia , Animais , Astrócitos/fisiologia , Contagem de Células/métodos , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Neurônios/fisiologia , Ratos , Ratos Wistar , Células-Tronco/fisiologiaRESUMO
Abstract Background: Hypertensive condition can lead to abnormalities in heart structure and electrical activity. The electrocardiogram (ECG) is a recording of the electrical activity of the heart and widely used to diagnose and detect heart problem. Objective: We conducted a comparative ECG analysis between two hypertension models (L-NAME and SHR) and their controls (Wistar and Wistar-Kyoto) at six and 15 th week of age. Methods: Blood pressure was measured at the end of the 15 th week, and electrocardiography was performed at six and 15 weeks of age in anaesthetized rats. Data normality was confirmed by Kolmogorov-Smirnov test followed by unpaired Student's t-test and the Mann-Whitney for parametric and non-parametric data, respectively. Results are expressed as mean ± SD. The accepted level of significance was set at p < 0.05. Results: L-NAME exhibited prolongation of JT and QT intervals and SHR showed a decrease in heart rate when compared to Wistar-Kyoto and L-NAME. Wistar-Kyoto exhibited short PR interval with increased QRS complex, and only QT prolongation at 15 weeks compared to Wistar. Conclusions: All the hypertension models used in this study featured an increase in blood pressure. However, while SHR showed cardiac dysfunction, L-NAME exhibited changes in ventricular performance. These results may guide future studies on different types and models of hypertension.
Assuntos
Animais , Masculino , Ratos , Eletrocardiografia/métodos , Hipertensão/complicações , Ratos Endogâmicos WKY , Ratos Wistar , NG-Nitroarginina Metil Éster/efeitos adversosRESUMO
Purpose: To analyze the serum levels of nitric oxide and correlate them with the levels of thiobarbituric acid reactive substances (TBARS) in liver, brain and spinal cord of animals using L-NAME and treated with hydroxyurea. Methods: Eighteen male albino Wistar rats were divided into three groups. NG-nitro-L-arginine methyl ester (L-NAME) was intraperitoneally administered to induce oxidative stress. TBARS and plasma nitric oxide levels were analyzed in all groups. Histopathology of the liver and vascular tissue was performed. Results: Statistically significant differences were seen in liver, brain and spinal cord TBARS levels. Conclusions: Following the use of L-NAME, hepatic tissue increased the number of Kupffer cells as oxidative stress and inflammatory response increased. The use of L-NAME caused an increase in lipid peroxidation products and, consequently, in oxidative stress in animals. Hydroxyurea doses of 35 mg / kg / day reduced TBARS values in liver, brain and spinal cord.(AU)
Assuntos
Animais , Ratos , Estresse Oxidativo , Fígado/efeitos dos fármacos , Cérebro/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Hidroxiureia/uso terapêutico , Anemia Falciforme/complicações , Anemia Falciforme/veterinária , Ratos WistarRESUMO
Abstract Purpose: To analyze the serum levels of nitric oxide and correlate them with the levels of thiobarbituric acid reactive substances (TBARS) in liver, brain and spinal cord of animals using L-NAME and treated with hydroxyurea. Methods: Eighteen male albino Wistar rats were divided into three groups. NG-nitro-L-arginine methyl ester (L-NAME) was intraperitoneally administered to induce oxidative stress. TBARS and plasma nitric oxide levels were analyzed in all groups. Histopathology of the liver and vascular tissue was performed. Results: Statistically significant differences were seen in liver, brain and spinal cord TBARS levels. Conclusions: Following the use of L-NAME, hepatic tissue increased the number of Kupffer cells as oxidative stress and inflammatory response increased. The use of L-NAME caused an increase in lipid peroxidation products and, consequently, in oxidative stress in animals. Hydroxyurea doses of 35 mg / kg / day reduced TBARS values in liver, brain and spinal cord.
Assuntos
Animais , Masculino , Ratos , Medula Espinal/metabolismo , Encéfalo/metabolismo , Estresse Oxidativo/fisiologia , Hidroxiureia/uso terapêutico , Anemia Falciforme/tratamento farmacológico , Fígado/metabolismo , Ratos Wistar , NG-Nitroarginina Metil Éster , Modelos Animais de Doenças , Anemia Falciforme/fisiopatologia , Anemia Falciforme/metabolismoRESUMO
Introducción: Desarrollar y potenciar las habilidades neuroquirúrgicas que se requieren en la disección del hueso temporal aplicado a la realización de abordajes quirúrgicos transtemporales, a través de modelos de bajo costo y aplicación sencilla. Materiales y métodos: Trabajamos sobre huesos temporales secos, con insumos hospitalarios descartables y con materiales básicos obtenidos en ferreterías. Se identificaron con silicona y teflón coloreados con acrílico, estructuras vasculares y nerviosas que forman los principales reparos anatómicos y se utiliza material sintético de látex adherido a la superficie endocraneal para recrear duramadre. Realizamos un estudio exhaustivo del hueso temporal con las diferentes estructuras anatómicas íntimamente relacionadas con él, abordándolo desde diferentes vistas. Una vez familiarizados con la anatomía, se ensayan abordajes neuroquirúrgicos y disecciones anatómicas profundizando el conocimiento sobre las estructuras relevantes no visibles previa a la disección. Discusión: En la formación neuroquirúrgica no solo importa el conocimiento teórico, sino que se requiere praxis eficaz aplicada al mismo y se logra sólo a través de auténticas experiencias, la cual da al practicante, la oportunidad de ensayar aspectos de un abordaje para lograr competencia previa a su aplicación en el paciente. Conclusión: El residente puede utilizar esta técnica de fácil acceso y bajo costo para realzar su experiencia de aprendizaje anatómico y fresado de huesos temporales y así poder discutir aspectos y ensayar un abordaje previo a una cirugía.
Introduction: Develop and enhance the neurosurgical skills required for temporal bone drilling applied to transtemporal surgical approaches through low cost and simple application models. Materials and methods: We worked on dry temporal bones with disposable hospital supplies and basic materials obtained in hardware stores. Vascular and nervous structures that form the main anatomical structures are identified with silicone and Teflon colored with acrylic and synthetic latex material is attached to the endocranial surface to recreate the dura mater. We carried out an exhaustive study of the temporal bone with the different anatomical structures intimately related to it, approaching it from different views. Once familiarized with the anatomy, neurosurgical approaches and anatomical dissections are practiced, increasing the understanding of the relevant structures not visible prior to dissection. Discussion: During neurosurgical training theoretical knowledge is not the only domain that matters, rather effective praxis applied to i t is needed and achieved only through authentic experiences, which gives the practitioner the opportunity to examine aspects of an approach in order to achieve expertise prior to its application to the patient. Conclusion: The resident can use this accessible and low cost technique to enhance their experience in anatomical learning and temporal b ones drilling and therefore, be able to discuss certain aspects and practice an approach prior to surgery.
Assuntos
Osso Temporal , Cirurgia Geral , Tecnologia de Baixo Custo , DissecaçãoRESUMO
It is known that autonomic modulation is responsive to ovarian hormone levels and that estrogen increases nitric oxide (NO) bioavailability. However, little is known about the interaction of nitric oxide synthase (NOS) isoforms with autonomic modulation, oxidative stress and cardiovascular risk in females. This study aimed to investigate cardiovascular, autonomic and oxidative parameters after selective NOS inhibition. A spectral analysis of systolic arterial pressure (SAP) and heart rate variability (HRV) was performed. NO levels, total antioxidant capacity (TRAP), lipid hydroperoxides (LOOH) and paraoxonase 1 (PON1) activity were measured in the plasma of rats treated with L-NG-nitroarginine methyl ester (L-NAME), S-methylisothiourea (SMT) or saline. Wistar rats, ovariectomized (OVX) with or without estradiol treatment (1mg/kg/day) or with a false ovariectomy (SHAM), were submitted to artery and vein catheterization. Cardiovascular parameters were evaluated before and after the administration of saline or NOS inhibitors. After 2h, plasma samples were collected for biochemical measurement. At baseline, cardiovascular and autonomic parameters were not different among the groups. L-NAME, the constitutive NOS isoform (cNOS) inhibitor, promoted an increase in mean arterial pressure (MAP) and a reduction in the low frequency band (LF) of SAP of SHAM rats, but this increase was smaller in OVX animals, which also showed a reduction in PON1 activity. The decreased activity of PON1 caused by L-NAME was prevented in the OVX+E group. SMT, an inducible NOS isoform (iNOS) inhibitor, promoted an increase in MAP and in the LF of SAP, in interbeat interval (IBI) parameters at LFnu and in LF/HF ratio of HRV in all groups, but the OVX+E had lower levels of NO when compared with the OVX group. Our data suggest that while cNOS contributes to maintaining the activity of PON1 in OVX rats, iNOS activity maintains the levels of NO in OVX+E rats.
Assuntos
Inibidores Enzimáticos/farmacologia , Estradiol/farmacologia , Estrogênios/farmacologia , Isotiurônio/análogos & derivados , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Animais , Antioxidantes , Arildialquilfosfatase/sangue , Sistema Nervoso Autônomo/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Isotiurônio/farmacologia , Peróxidos Lipídicos/sangue , Óxido Nítrico/sangue , Ovariectomia , Ratos , Ratos WistarRESUMO
ABSTRACT Purpose To investigate the lower urinary tract changes in mice treated with L-NAME, a non-selective competitive inhibitor of nitric oxide synthase (NOS), or aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS), after 5 weeks of partial bladder outlet obstruction (BOO), in order to evaluate the role of constitutive and non-constitutive NOS in the pathogenesis of this experimental condition. Materials and Methods C57BL6 male mice were partially obstructed and randomly allocated into 6 groups: Sham, Sham + L-NAME, Sham + aminoguanidine, BOO, BOO + L-NAME and BOO + aminoguanidine. After 5 weeks, bladder weight was obtained and cystometry and tissue bath contractile studies were performed. Results BOO animals showed increase of non-voiding contractions (NVC) and bladder capacity, and also less contractile response to Carbachol and Electric Field Stimulation. Inhibition of NOS isoforms improved bladder capacity and compliance in BOO animals. L-NAME caused more NVC, prevented bladder weight gain and leaded to augmented contractile responses at muscarinic and electric stimulation. Aminoguanidine diminished NVC, but did not avoid bladder weight gain in BOO animals and did not improve contractile responses. Conclusion It can be hypothesized that chronic inhibition of three NOS isoforms in BOO animals leaded to worsening of bladder function, while selective inhibition of iNOS did not improve responses, what suggests that, in BOO animals, alterations are related to constitutive NOS.
Assuntos
Animais , Masculino , Obstrução do Colo da Bexiga Urinária/tratamento farmacológico , Óxido Nítrico Sintase/antagonistas & inibidores , NG-Nitroarginina Metil Éster/farmacologia , Inibidores Enzimáticos/farmacologia , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Guanidinas/farmacologia , Óxido Nítrico/antagonistas & inibidores , Pressão , Fatores de Tempo , Micção/efeitos dos fármacos , Micção/fisiologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Distribuição Aleatória , Reprodutibilidade dos Testes , Resultado do Tratamento , NG-Nitroarginina Metil Éster/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Guanidinas/uso terapêutico , Camundongos Endogâmicos C57BL , Contração Muscular/efeitos dos fármacosRESUMO
PURPOSE: To investigate the lower urinary tract changes in mice treated with L-NAME, a non-selective competitive inhibitor of nitric oxide synthase (NOS), or aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS), after 5 weeks of partial bladder outlet obstruction (BOO), in order to evaluate the role of constitutive and non-constitutive NOS in the pathogenesis of this experimental condition. MATERIALS AND METHODS: C57BL6 male mice were partially obstructed and randomly allocated into 6 groups: Sham, Sham + L-NAME, Sham + aminoguanidine, BOO, BOO + L-NAME and BOO + aminoguanidine. After 5 weeks, bladder weight was obtained and cystometry and tissue bath contractile studies were performed. RESULTS: BOO animals showed increase of non-voiding contractions (NVC) and bladder capacity, and also less contractile response to Carbachol and Electric Field Stimulation. Inhibition of NOS isoforms improved bladder capacity and compliance in BOO animals. L-NAME caused more NVC, prevented bladder weight gain and leaded to augmented contractile responses at muscarinic and electric stimulation. Aminoguanidine diminished NVC, but did not avoid bladder weight gain in BOO animals and did not improve contractile responses. CONCLUSION: It can be hypothesized that chronic inhibition of three NOS isoforms in BOO animals leaded to worsening of bladder function, while selective inhibition of iNOS did not improve responses, what suggests that, in BOO animals, alterations are related to constitutive NOS.
Assuntos
Inibidores Enzimáticos/farmacologia , Guanidinas/farmacologia , Sintomas do Trato Urinário Inferior/tratamento farmacológico , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico/antagonistas & inibidores , Obstrução do Colo da Bexiga Urinária/tratamento farmacológico , Animais , Inibidores Enzimáticos/uso terapêutico , Guanidinas/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL , Contração Muscular/efeitos dos fármacos , NG-Nitroarginina Metil Éster/uso terapêutico , Pressão , Distribuição Aleatória , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Micção/efeitos dos fármacos , Micção/fisiologiaRESUMO
Today, there is enormous progress in understanding the function of glial cells, including astroglia, oligodendroglia, Schwann cells, and microglia. Around 150 years ago, glia were viewed as a glue among neurons. During the course of the twentieth century, microglia were discovered and neuroscientists' views evolved toward considering glia only as auxiliary cells of neurons. However, over the last two to three decades, glial cells' importance has been reconsidered because of the evidence on their involvement in defining central nervous system architecture, brain metabolism, the survival of neurons, development and modulation of synaptic transmission, propagation of nerve impulses, and many other physiological functions. Furthermore, increasing evidence shows that glia are involved in the mechanisms of a broad spectrum of pathologies of the nervous system, including some psychiatric diseases, epilepsy, and neurodegenerative diseases to mention a few. It appears safe to say that no neurological disease can be understood without considering neuron-glia crosstalk. Thus, this book aims to show different roles played by glia in the healthy and diseased nervous system, highlighting some of their properties while considering that the various glial cell types are essential components not only for cell function and integration among neurons, but also for the emergence of important brain homeostasis.
Assuntos
Astrócitos/fisiologia , Microglia/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso , Neurônios/fisiologia , Oligodendroglia/fisiologia , Células de Schwann/fisiologia , Astrócitos/citologia , Epilepsia/patologia , Epilepsia/fisiopatologia , Humanos , Microglia/citologia , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Sistema Nervoso/patologia , Sistema Nervoso/fisiopatologia , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia , Neurônios/citologia , Óxido Nítrico/fisiologia , Oligodendroglia/citologia , Estresse Oxidativo , Células de Schwann/citologia , Sinapses/fisiologia , Transmissão Sináptica/fisiologiaRESUMO
BACKGROUND: Liposomes are concentric lipid vesicles that allow a sustained release of entrapped substances. GABA (γ-aminobutyric acid) is the most prevalent inhibitory neurotransmitter in the central nervous system. NEW METHOD: Using GABA-containing liposomes (GL) prepared by the freeze-thawing method, we determined the effect of sustained release of GABA on expression of neuronal nitric oxide synthase (nNOS) and GABAA receptor (GABAAR) in an in vitro neuronal model. RESULTS: Neuronal cell line NG108-15 treated with different doses of GL during 24h showed an increase in expression of GABAAR (54 and 50% with 10 and 20ng doses, respectively) and nNOS (138, 157 and 165% with 20, 50 and 100ng doses, respectively) compared with cells treated with empty liposomes (EL). Additionally, cells treated with 50ng of GL showed an increase in GABAAR (23%) after 1h followed by an increase in nNOS (55, 46 and 55%) at 8, 12 and 24h time points, respectively. Immunofluorescence experiments confirmed an increase in nNOS (134%) and basal intracellular levels of nitric oxide (84%) after GL treatment. Further, treatment of cells with GL showed a decrease in expression of a protein inhibitor of nNOS (PIN) (26, 66 and 57% with 20, 50 and 100ng doses respectively) compared with control. COMPARISON WITH EXISTING METHODS: This is first demonstration for the development of GL that allows sustained slow release of this neurotransmitter. CONCLUSION: These results suggest that a slow release of GABA can change the expression of nNOS possibly via alteration in PIN levels in neuronal cells.
Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lipossomos/administração & dosagem , Óxido Nítrico Sintase Tipo I/metabolismo , Ácido gama-Aminobutírico/administração & dosagem , Animais , Proteína de Ligação a CREB/metabolismo , Linhagem Celular Tumoral , Dineínas do Citoplasma/metabolismo , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Ácido Glutâmico/farmacologia , Lipossomos/farmacologia , Camundongos , Neuroblastoma/patologia , Nitritos/metabolismo , RNA Interferente Pequeno/farmacologia , Ratos , Receptores de GABA-A/metabolismo , Fatores de Tempo , Ácido gama-Aminobutírico/farmacologiaRESUMO
RESUMO Introdução: A capacidade intrínseca para o exercício aeróbico está relacionada com o inotropismo cardíaco. Por outro lado, a participação do óxido nítrico (NO) como mensageiro intracelular sobre a dinâmica do Ca2+ ainda permanece desconhecida em ratos com diferentes capacidades intrínsecas para o exercício. Objetivo: Avaliar se o NO modula diferentemente o transiente intracelular de Ca2+ e liberações espontâneas de Ca2+(sparks) em cardiomiócitos de ratos com diferentes capacidades intrínsecas para o exercício. Métodos: Ratos machos Wistar foram selecionados como desempenho padrão (DP) e alto desempenho (AD), de acordo com a capacidade de exercício até a fadiga, mensurada através de teste de esforço progressivo em esteira. Os cardiomiócitos dos ratos foram utilizados para determinar o transiente intracelular de Ca2+ e Ca2+sparks em microscópio confocal. Para estimar a contribuição do NO foi utilizado o inibidor das sínteses do NO (L-NAME, 100 µM). Os dados foram analisados através de ANOVA two-way seguido do pós-teste de Tukey e apresentados como médias ± EPM. Resultados: Os cardiomiócitos de ratos AD exibiram aumentos na amplitude do transiente de Ca2+ em comparação aos DP. Entretanto, o L-NAME aumentou a amplitude do transiente de Ca2+ somente em ratos DP. Não foram encontradas diferenças na constante de tempo de decaimento do transiente de Ca2+ (t) em cardiomiócitos de ratos com DP e AP, contudo, a administração do L-NAME diminuiu o t em cardiomiócitos em ambos os grupos. cardiomiócitos de ratos AD apresentaram menor amplitude e frequência de Ca2+sparks em comparação ao grupo DP. A administração de L-NAME aumentou a amplitude de Ca2+sparks em cardiomiócitos do grupo AD. Conclusão: O NO modula o transiente de Ca2+ e as sparks de Ca2+ em cardiomiócitos de ratos com diferentes capacidades intrínsecas para o exercício.
ABSTRACT Introduction: The intrinsic capacity to aerobic exercise is associated with cardiac inotropism. On the other hand, the contribution of nitric oxide (NO) as an intracellular messenger on Ca2+ dynamics remains unknown in rats with different intrinsic capacities to exercise. Objective: To evaluate whether NO modulates differently Ca2+ intracellular transient and spontaneous Ca2+ releases (sparks) in cardiomyocytes of rats with different intrinsic capacities to exercise. Methods: Male Wistar rats were selected as standard-performance (SP) and high-performance (HP), according to the exercise capacity until fatigue, assessed through a treadmill progressive stress test. Cardiomyocytes of rats were used to determine Ca2+ intracellular transient and Ca2+ sparks evaluated using confocal microscope. To estimate NO contribution, a NO synthase inhibitor (L-NAME, 100 µM) was used. Data were analyzed through two-way ANOVA followed by Tukey's post hoc test and expressed as means ± SEM. Results: Cardiomyocytes of HP rats exhibited higher Ca2+ transient amplitude compared to SP. However, L-NAME increased Ca2+ transient amplitude only in SP rats. No differences were found in Ca2+ transient decay time constant ( t) in cardiomyocytes of SP and HP rats. However, administration of L-NAME caused reduction of tin cardiomyocytes of both groups. Lower amplitude and frequency of Ca2+ sparks were found in cardiomyocytes of HS rats compared to SP group. Administration of L-NAME increased the amplitude of Ca2+ sparks in cardiomyocytes of the HP group. Conclusion: NO modulates Ca2+ transient and Ca2+ sparks in cardiomyocytes of rats with different intrinsic exercise capacities.
RESUMEN Introducción: La capacidad intrínseca para el ejercicio aeróbico está relacionada con el inotropismo cardiaco. Por otro lado, todavía se desconoce la contribución del óxido nítrico (ON) como mensajero intracelular sobre la dinámica del Ca2+ en ratones con diferentes capacidades intrínsecas para el ejercicio. Objetivo: Evaluar si el ON modula diferencialmente la variación transitoria intracelular de Ca2+ y las liberaciones espontaneas de Ca2+ (sparks) en cardiomiocitos de ratones con diferentes capacidades intrínsecas para el ejercicio. Métodos: Ratones machos Wistar fueron seleccionados como desempeño estándar (DE) y alto desempeño (AD), de acuerdo con la capacidad de ejercicio hasta la fatiga, medida a través del test de fuerza progresiva en la caminadora o cinta eléctrica. Los cardiomiocitos de los ratones fueron utilizados para determinar el tránsito intracelular y sparks de Ca2+ evaluados en microscopio confocal. Para estimar la contribución del ON fue utilizado un inhibidor de síntesis del ON (L-NAME, 100 µM). Los datos fueron analizados a través de un ANOVA two-way seguido de un post-test Tukey y presentados como promedios ± EPM. Resultados: Los cardiomiocitos de ratones AD mostraron aumento en la amplitud de la variación transitoria de Ca2+ en comparación con los DE. Así mismo, el L-NAME incremento la amplitud transitoria de Ca2+ solamente en ratones DE. No se encontraron diferencias en la constante del tiempo de decaimiento de la variación transitoria ( t ) de Ca2+ en cardiomiocitos de ratones DE e AD. Todavía, la administración de L-NAME mostro una reducción en el t en cardiomiocitos de ambos los grupos. Cardiomiocitos de ratones AD presentaron menor amplitud y frecuencia de sparks de Ca2+ en comparación al grupo DE. La administración de L-NAME incrementó la amplitud de sparks de Ca2+ en cardiomiocitos del grupo AD. Conclusión: El ON modula la variación de Ca2+ y sparks de Ca2+ en cardiomiocitos de ratones con diferentes capacidades intrínsecas para el ejercicio.
RESUMO
Biogas digestates contain valuable nutrients but also have high water contents. Di-gestates were sampled from two different biogas facilities before and after solid-liquid separation and were analyzed with regard to their composition and phosphorus (P) fractions. Additionally, to investigate the P fertilizer effects of these digestates in comparison with undigested slurry or TripleSuper-P (TSP), they were applied in a pot experiment (6 kg soil per pot) in an amount corresponding to 200 mg P per pot in combination with various crops (amaranth, maize, maize + beans mixed cropping, sorghum). A separation of digestates resulted in higher P concentrations of the solid fraction in comparison with the liquid fraction. The proportion of the readily soluble P fractions (H2O-P, NaHCO3-P) to the total P was higher than 70 % in all digestates. The digestates increased P uptake of the tested crops and concentrations of bioavailable P in the soil to the same extent as highly soluble TSP. Activities of soil enzymes were lower after application of the digestates in comparison to unfermented slurry. The fertilizer management of digestates can be improved by a solid-liquid separation since the solid fraction showed a relatively high concentration of P resulting in a reduction in application doses required to meet the P demands of crops.