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1.
Nat Commun ; 12(1): 1990, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790272

RESUMO

A crucial phase in the infection process, which remains poorly understood, is the localization of suitable host cells by bacteria. It is often assumed that chemotaxis plays a key role during this phase. Here, we report a quantitative study on how Salmonella Typhimurium search for T84 human colonic epithelial cells. Combining time-lapse microscopy and mathematical modeling, we show that bacteria can be described as chiral active particles with strong active speed fluctuations, which are of biological, as opposed to thermal, origin. We observe that there exists a giant range of inter-individual variability of the bacterial exploring capacity. Furthermore, we find Salmonella Typhimurium does not exhibit biased motion towards the cells and show that the search time statistics is consistent with a random search strategy. Our results indicate that in vitro localization of host cells, and also cell infection, are random processes, not involving chemotaxis, that strongly depend on bacterial motility parameters.


Assuntos
Algoritmos , Aderência Bacteriana/fisiologia , Células Epiteliais/metabolismo , Salmonella typhimurium/metabolismo , Linhagem Celular Tumoral , Quimiotaxia/fisiologia , Células Epiteliais/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Locomoção/fisiologia , Microscopia/métodos , Movimento (Física) , Salmonella typhimurium/fisiologia , Imagem com Lapso de Tempo/métodos
2.
Int J Mol Sci ; 22(4)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672911

RESUMO

The Gram-negative bacterium Flavobacterium johnsoniae employs gliding motility to move rapidly over solid surfaces. Gliding involves the movement of the adhesin SprB along the cell surface. F. johnsoniae spreads on nutrient-poor 1% agar-PY2, forming a thin film-like colony. We used electron microscopy and time-lapse fluorescence microscopy to investigate the structure of colonies formed by wild-type (WT) F. johnsoniae and by the sprB mutant (ΔsprB). In both cases, the bacteria were buried in the extracellular polymeric matrix (EPM) covering the top of the colony. In the spreading WT colonies, the EPM included a thick fiber framework and vesicles, revealing the formation of a biofilm, which is probably required for the spreading movement. Specific paths that were followed by bacterial clusters were observed at the leading edge of colonies, and abundant vesicle secretion and subsequent matrix formation were suggested. EPM-free channels were formed in upward biofilm protrusions, probably for cell migration. In the nonspreading ΔsprB colonies, cells were tightly packed in layers and the intercellular space was occupied by less matrix, indicating immature biofilm. This result suggests that SprB is not necessary for biofilm formation. We conclude that F. johnsoniae cells use gliding motility to spread and maturate biofilms.


Assuntos
Adesinas Bacterianas/metabolismo , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Flavobacterium/fisiologia , Locomoção/fisiologia , Proteínas de Bactérias/genética , Flavobacterium/genética , Flavobacterium/ultraestrutura , Locomoção/genética , Microscopia Eletrônica de Transmissão/métodos , Microscopia de Fluorescência/métodos , Mutação , Imagem com Lapso de Tempo/métodos
3.
Nat Commun ; 12(1): 1925, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771986

RESUMO

A spinal cord injury usually spares some components of the locomotor circuitry. Deep brain stimulation (DBS) of the midbrain locomotor region and epidural electrical stimulation of the lumbar spinal cord (EES) are being used to tap into this spared circuitry to enable locomotion in humans with spinal cord injury. While appealing, the potential synergy between DBS and EES remains unknown. Here, we report the synergistic facilitation of locomotion when DBS is combined with EES in a rat model of severe contusion spinal cord injury leading to leg paralysis. However, this synergy requires high amplitudes of DBS, which triggers forced locomotion associated with stress responses. To suppress these undesired responses, we link DBS to the intention to walk, decoded from cortical activity using a robust, rapidly calibrated unsupervised learning algorithm. This contingency amplifies the supraspinal descending command while empowering the rats into volitional walking. However, the resulting improvements may not outweigh the complex technological framework necessary to establish viable therapeutic conditions.


Assuntos
Estimulação Encefálica Profunda/métodos , Modelos Animais de Doenças , Vértebras Lombares/fisiopatologia , Córtex Motor/fisiopatologia , Traumatismos da Medula Espinal/terapia , Medula Espinal/fisiopatologia , Caminhada/fisiologia , Animais , Estimulação Elétrica/métodos , Feminino , Humanos , Locomoção/fisiologia , Mesencéfalo/fisiopatologia , Neurônios/fisiologia , Ratos Endogâmicos Lew , Traumatismos da Medula Espinal/fisiopatologia
4.
Neuron ; 109(7): 1188-1201.e7, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33577748

RESUMO

Proprioception is essential for behavior and provides a sense of our body movements in physical space. Proprioceptor organs are thought to be only in the periphery. Whether the central nervous system can intrinsically sense its own movement remains unclear. Here we identify a segmental organ of proprioception in the adult zebrafish spinal cord, which is embedded by intraspinal mechanosensory neurons expressing Piezo2 channels. These cells are late-born, inhibitory, commissural neurons with unique molecular and physiological profiles reflecting a dual sensory and motor function. The central proprioceptive organ locally detects lateral body movements during locomotion and provides direct inhibitory feedback onto rhythm-generating interneurons responsible for the central motor program. This dynamically aligns central pattern generation with movement outcome for efficient locomotion. Our results demonstrate that a central proprioceptive organ monitors self-movement using hybrid neurons that merge sensory and motor entities into a unified network.


Assuntos
Retroalimentação Sensorial/fisiologia , Movimento/fisiologia , Propriocepção/fisiologia , Peixe-Zebra/fisiologia , Animais , Geradores de Padrão Central/fisiologia , Feminino , Interneurônios/fisiologia , Canais Iônicos/fisiologia , Locomoção/fisiologia , Masculino , Mecanotransdução Celular , Neurônios Motores/fisiologia , Rede Nervosa/citologia , Rede Nervosa/fisiologia , RNA/genética , Células Receptoras Sensoriais/fisiologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/fisiologia , Tomografia Computadorizada por Raios X , Proteínas de Peixe-Zebra/fisiologia
5.
Nat Commun ; 12(1): 781, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536416

RESUMO

After complete spinal cord injuries (SCI), spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. However, it is unknown whether selective manipulation of these circuits can restore locomotor function in the absence of brain-derived inputs. By taking advantage of the compromised blood-spinal cord barrier following SCI, we optimized a set of procedures in which AAV9 vectors administered via the tail vein efficiently transduce neurons in lesion-adjacent spinal segments after a thoracic crush injury in adult mice. With this method, we used chemogenetic actuators to alter the excitability of propriospinal neurons in the thoracic cord of the adult mice with a complete thoracic crush injury. We showed that activating these thoracic neurons enables consistent and significant hindlimb stepping improvement, whereas direct manipulations of the neurons in the lumbar spinal cord led to muscle spasms without meaningful locomotion. Strikingly, manipulating either excitatory or inhibitory propriospinal neurons in the thoracic levels leads to distinct behavioural outcomes, with preferential effects on standing or stepping, two key elements of the locomotor function. These results demonstrate a strategy of engaging thoracic propriospinal neurons to improve hindlimb function and provide insights into optimizing neuromodulation-based strategies for treating SCI.


Assuntos
Dependovirus/genética , Membro Posterior/fisiopatologia , Locomoção/fisiologia , Neurônios/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Animais , Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Clozapina/análogos & derivados , Vetores Genéticos/genética , Membro Posterior/inervação , Locomoção/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia
6.
Neurosci Lett ; 745: 135617, 2021 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-33421492

RESUMO

Hepatic encephalopathy (HE) is a cerebral function alteration in patients with liver dysfunction. The present study aimed to evaluate the therapeutic effects of thymoquinone (TQ) on behavioral deficits and its possible mechanism(s) in a thioacetamide (TAA)-induced HE model. HE was induced in male Wistar rats by intraperitoneal (i.p.) injection of TAA (200 mg/kg) for once every 48 h for 14 consecutive days. Thymoquinone (5, 10, and 20 mg/kg) was administered for seven consecutive days (i.p.) after HE induction. Anxiety and depression-like behaviors assessed by standard paradigms respectively. Finally, their brain hippocampus sections prepared to evaluate the oxidative stress changes in rats. Data showed treatment HE rats with TQ ameliorated anxiety and depression-like behaviors. TQ administration also reduced oxidative stress due to its potential to enhance the levels of glutathione-peroxidase (GPx), catalase (CAT), and total thiol content in the hippocampus. These findings suggest that TQ has notable effects against acute hepatic failure and HE complications through modulation of oxidative stress.


Assuntos
Benzoquinonas/uso terapêutico , Encefalopatia Hepática/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Tioacetamida/toxicidade , Animais , Benzoquinonas/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Encefalopatia Hepática/induzido quimicamente , Encefalopatia Hepática/metabolismo , Hipocampo/química , Hipocampo/metabolismo , Locomoção/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Wistar
8.
Nat Commun ; 12(1): 535, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33483493

RESUMO

Optogenetics is a powerful technique that allows target-specific spatiotemporal manipulation of neuronal activity for dissection of neural circuits and therapeutic interventions. Recent advances in wireless optogenetics technologies have enabled investigation of brain circuits in more natural conditions by releasing animals from tethered optical fibers. However, current wireless implants, which are largely based on battery-powered or battery-free designs, still limit the full potential of in vivo optogenetics in freely moving animals by requiring intermittent battery replacement or a special, bulky wireless power transfer system for continuous device operation, respectively. To address these limitations, here we present a wirelessly rechargeable, fully implantable, soft optoelectronic system that can be remotely and selectively controlled using a smartphone. Combining advantageous features of both battery-powered and battery-free designs, this device system enables seamless full implantation into animals, reliable ubiquitous operation, and intervention-free wireless charging, all of which are desired for chronic in vivo optogenetics. Successful demonstration of the unique capabilities of this device in freely behaving rats forecasts its broad and practical utilities in various neuroscience research and clinical applications.


Assuntos
Eletrodos Implantados , Optogenética/instrumentação , Optogenética/métodos , Tecnologia sem Fio , Animais , Encéfalo/fisiologia , Estimulação Encefálica Profunda/métodos , Fenômenos Eletromagnéticos , Humanos , Locomoção/fisiologia , Masculino , Ratos Sprague-Dawley
9.
Nat Commun ; 12(1): 391, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452250

RESUMO

Spinal cord injury (SCI) often causes severe and permanent disabilities due to the regenerative failure of severed axons. Here we report significant locomotor recovery of both hindlimbs after a complete spinal cord crush. This is achieved by the unilateral transduction of cortical motoneurons with an AAV expressing hyper-IL-6 (hIL-6), a potent designer cytokine stimulating JAK/STAT3 signaling and axon regeneration. We find collaterals of these AAV-transduced motoneurons projecting to serotonergic neurons in both sides of the raphe nuclei. Hence, the transduction of cortical neurons facilitates the axonal transport and release of hIL-6 at innervated neurons in the brain stem. Therefore, this transneuronal delivery of hIL-6 promotes the regeneration of corticospinal and raphespinal fibers after injury, with the latter being essential for hIL-6-induced functional recovery. Thus, transneuronal delivery enables regenerative stimulation of neurons in the deep brain stem that are otherwise challenging to access, yet highly relevant for functional recovery after SCI.


Assuntos
Terapia Genética/métodos , Interleucina-6/genética , Locomoção/fisiologia , Regeneração Nervosa/fisiologia , Traumatismos da Medula Espinal/terapia , Animais , Axônios/fisiologia , Córtex Cerebral/citologia , Córtex Cerebral/fisiologia , Dependovirus/genética , Modelos Animais de Doenças , Feminino , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Humanos , Janus Quinases/metabolismo , Masculino , Camundongos , Camundongos Knockout , Microinjeções , Neurônios Motores/fisiologia , PTEN Fosfo-Hidrolase/genética , Núcleos da Rafe/citologia , Núcleos da Rafe/fisiologia , Recuperação de Função Fisiológica , Fator de Transcrição STAT3/metabolismo , Neurônios Serotoninérgicos/fisiologia , Índice de Gravidade de Doença , Transdução de Sinais , Medula Espinal/citologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/fisiopatologia , Transdução Genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-33401532

RESUMO

Hamstring muscle injury is common in female soccer players. Changes affecting eccentric strength, flexibility, and the quadriceps-hamstring contraction cycle are risk factors associated with this type of injury. Methods: Seventeen soccer players were randomized to two groups: experimental (plyometric and eccentric exercises without external loads) and control (eccentric exercises without external loads). Eighteen sessions were scheduled over 6 weeks. The exercise program included three plyometric exercises (single-leg squat and lunge, 180 jump, and broad jump stick landing) and three eccentric exercises (Nordic hamstring exercise, diver, and glider). Dependent variables were jumping height (My Jump 2.0 App) and anterior, posteromedial, and posterolateral lower limb stability (Y-Balance test). Results: Following intervention, improvements were found in anterior and posteromedial stability (p = 0.04) in the experimental group. Posterolateral stability improved in athletes included in the control group (p = 0.02). There were differences in the repeated measures analysis for all variables, with no changes in group interaction (p > 0.05). Conclusions: Eccentric exercises, either combined with plyometric exercises or alone, can improve lower limb stability. No changes in jump height were noted in either group. There were no differences between the two groups in the variables studied. Future studies should analyze the effect of external loads on jumping stability and height in the performance of plyometric exercises.


Assuntos
Exercício Físico , Locomoção , Exercício Pliométrico , Futebol , Adulto , Exercício Físico/fisiologia , Feminino , Humanos , Locomoção/fisiologia , Projetos Piloto , Método Simples-Cego , Futebol/fisiologia , Adulto Jovem
11.
Am J Phys Anthropol ; 174(2): 327-351, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33368154

RESUMO

OBJECTIVES: Many primates change their locomotor behavior as they mature from infancy to adulthood. Here we investigate how long bone cross-sectional geometry in Pan, Gorilla, Pongo, Hylobatidae, and Macaca varies in shape and form over ontogeny, including whether specific diaphyseal cross sections exhibit signals of periosteal adaptation or canalization. MATERIALS AND METHODS: Diaphyseal cross sections were analyzed in an ontogenetic series across infant, juvenile, and adult subgroups. Three-dimensional laser-scanned long bone models were sectioned at midshaft (50% of biomechanical length) and distally (20%) along the humerus and femur. Traditional axis ratios acted as indices of cross-sectional circularity, while geometric morphometric techniques were used to study cross-sectional allometry and ontogenetic trajectory. RESULTS: The humeral midshaft is a strong indicator of posture and locomotor profile in the sample across development, while the mid-femur appears more reflective of shifts in size. By comparison, the distal diaphyses of both limb elements are more ontogenetically constrained, where periosteal shape is largely static across development relative to size, irrespective of a given taxon's behavior or ecology. DISCUSSION: Primate limb shape is not only highly variable between taxa over development, but at discrete humeral and femoral diaphyseal locations. Overall, periosteal shape of the humeral and femoral midshaft cross sections closely reflects ontogenetic transitions in behavior and size, respectively, while distal shape in both bones appears more genetically constrained across intraspecific development, regardless of posture or size. These findings support prior research on tradeoffs between function and safety along the limbs.


Assuntos
Tamanho Corporal/fisiologia , Diáfises/anatomia & histologia , Fêmur/anatomia & histologia , Hominidae , Locomoção/fisiologia , Fatores Etários , Anatomia Transversal , Animais , Antropologia Física , Antropometria , Hominidae/anatomia & histologia , Hominidae/fisiologia , Úmero/anatomia & histologia
12.
Methods Mol Biol ; 2191: 201-220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32865747

RESUMO

Zebrafish are an excellent model organism to study many aspects of vertebrate sensory encoding and behavior. Their escape responses begin with a C-shaped body bend followed by several swimming bouts away from the potentially threatening stimulus. This highly stereotyped motor behavior provides a model for studying startle reflexes and the neural circuitry underlying multisensory encoding and locomotion. Channelrhodopsin (ChR2) can be expressed in the lateral line and ear hair cells of zebrafish and can be excited in vivo to elicit these rapid forms of escape. Here we review our methods for studying transgenic ChR2-expressing zebrafish larvae, including screening for positive expression of ChR2 and recording field potentials and high-speed videos of optically evoked escape responses. We also highlight important features of the acquired data and provide a brief review of other zebrafish research that utilizes or has the potential to benefit from ChR2 and optogenetics.


Assuntos
Channelrhodopsins/genética , Potenciais Evocados/genética , Neurônios/metabolismo , Optogenética/métodos , Animais , Animais Geneticamente Modificados/genética , Channelrhodopsins/fisiologia , Potenciais Evocados/fisiologia , Células Ciliadas Auditivas/metabolismo , Larva/fisiologia , Locomoção/genética , Locomoção/fisiologia , Neurônios/patologia , Reflexo de Sobressalto/fisiologia , Natação/fisiologia , Peixe-Zebra/genética , Peixe-Zebra/fisiologia
13.
J Neurosci ; 41(7): 1529-1552, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33328292

RESUMO

The basal ganglia are important for movement and reinforcement learning. Using mice of either sex, we found that the main basal ganglia GABAergic output in the midbrain, the substantia nigra pars reticulata (SNr), shows movement-related neural activity during the expression of a negatively reinforced signaled locomotor action known as signaled active avoidance; this action involves mice moving away during a warning signal to avoid a threat. In particular, many SNr neurons deactivate during active avoidance responses. However, whether SNr deactivation has an essential role driving or regulating active avoidance responses is unknown. We found that optogenetic excitation of SNr or striatal GABAergic fibers that project to an area in the pedunculopontine tegmentum (PPT) within the midbrain locomotor region abolishes signaled active avoidance responses, while optogenetic inhibition of SNr cells (mimicking the SNr deactivation observed during an active avoidance behavior) serves as an effective conditioned stimulus signal to drive avoidance responses by disinhibiting PPT neurons. However, preclusion of SNr deactivation, or direct inhibition of SNr fibers in the PPT, does not impair the expression of signaled active avoidance, indicating that SNr output does not drive the expression of a signaled locomotor action mediated by the midbrain. Consistent with a permissive regulatory role, SNr output provides information about the state of the ongoing action to downstream structures that mediate the action.SIGNIFICANCE STATEMENT During signaled active avoidance behavior, subjects move away to avoid a threat when directed by an innocuous sensory stimulus. Excitation of GABAergic cells in the substantia nigra pars reticulata (SNr), the main output of the basal ganglia, blocks signaled active avoidance, while inhibition of SNr cells is an effective stimulus to drive active avoidance. Interestingly, many SNr cells inhibit their firing during active avoidance responses, suggesting that SNr inhibition could be driving avoidance responses by disinhibiting downstream areas. However, interfering with the modulation of SNr cells does not impair the behavior. Thus, SNr may regulate the active avoidance movement in downstream areas that mediate the behavior, but does not drive it.


Assuntos
Gânglios da Base/fisiologia , Locomoção/fisiologia , Mesencéfalo/fisiologia , Animais , Aprendizagem da Esquiva/fisiologia , Feminino , Masculino , Camundongos , Fibras Nervosas/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Optogenética , Parte Reticular da Substância Negra/fisiologia , Núcleo Tegmental Pedunculopontino/fisiologia , Ácido gama-Aminobutírico/fisiologia
14.
Neurosci Lett ; 743: 135563, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33359046

RESUMO

N-myc downstream-regulated gene 2 (NDRG2), a member of the NDRG family, has multiple functions in cell proliferation, differentiation, and stress responses, and is predominantly expressed by astrocytes in the central nervous system. Previous studies including ours demonstrated that NDRG2 is involved in various central nervous system pathologies. However, the significance of NDRG2 in neurodevelopment is not fully understood. Here, we investigated the expression profile of NDRG2 during postnatal brain development, the role of NDRG2 in social behavior, and transcriptome changes in the brain of NDRG2-deficient mice. NDRG2 expression in the brain increased over time from postnatal day 1 to adulthood. Deletion of NDRG2 resulted in abnormal social behavior, as indicated by reduced exploratory activity toward a novel mouse in a three-chamber social interaction test. Microarray analysis identified genes differentially expressed in the NDRG2-deficient brain, and upregulated gene expression of Bmp4 and Per2 was confirmed by quantitative PCR analysis. Expression of both these genes and the encoded proteins increased over time during postnatal brain development, similar to NDRG2. Gene expression of Bmp4 and Per2 was upregulated in cultured astrocytes isolated from NDRG2-deficient mice. These results suggest that NDRG2 contributes to brain development required for proper social behavior by modulating gene expression in astrocytes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Comportamento Social , Animais , Proteína Morfogenética Óssea 4/biossíntese , Proteína Morfogenética Óssea 4/genética , Células Cultivadas , Expressão Gênica , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Circadianas Period/biossíntese , Proteínas Circadianas Period/genética
15.
Neurosci Lett ; 743: 135560, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33359047

RESUMO

Epilepsy is a chronic neurological condition that affects 1%-2% of the world population. Although research about the disease is advancing and a wide variety of drugs is available, about 30 % of patients have refractory epilepsy which cannot be controlled with the most common drugs. This highlights the need for a better understanding of the disorder and new types of treatment for it. Against this backdrop, a growing body of evidence has reported that inflammation may play a role both in the origin and in the progression of seizures. It has shown a tendency to be both the root and the result of epilepsy. This investigation aimed to assess the impact of prednisolone, a steroidal anti-inflammatory drug, in an animal model of pentylenetetrazole (PTZ)-induced seizures, at 1 mg/kg and 5 mg/kg doses. We also examined the degree of seizure severity and the modulation of pro-inflammatory cytokines in the treated animals. Four treatment groups were used (saline, diazepam, prednisolone 1 mg/kg, and prednisolone 5 mg/kg) and, in addition to their own daily treatments, subconvulsant doses of pentylenetetrazole (25 mg/kg) were administered every other day during a test protocol that lasted 14 days. After treatment, the cytokines interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured in the animals' sera, hippocampi, and prefrontal cortices. Animals treated with prednisolone presented less severe seizures than the animals in the saline group, and there was a decrease in pro-inflammatory cytokine levels in central structures, but not peripheral ones. In short, an animal model of chemically-induced epileptic seizures was used, in which the animals were treated with doses of prednisolone, and these animals presented less severe seizures than the negative control group (saline), in addition to showing decreased levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α, in the hippocampi and prefrontal cortices, but not the sera.


Assuntos
Anti-Inflamatórios/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Locomoção/efeitos dos fármacos , Pentilenotetrazol/toxicidade , Prednisolona/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Mediadores da Inflamação/metabolismo , Locomoção/fisiologia , Masculino , Prednisolona/farmacologia , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/metabolismo , Resultado do Tratamento
16.
Nat Struct Mol Biol ; 28(1): 29-37, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33318703

RESUMO

In motile cilia, a mechanoregulatory network is responsible for converting the action of thousands of dynein motors bound to doublet microtubules into a single propulsive waveform. Here, we use two complementary cryo-EM strategies to determine structures of the major mechanoregulators that bind ciliary doublet microtubules in Chlamydomonas reinhardtii. We determine structures of isolated radial spoke RS1 and the microtubule-bound RS1, RS2 and the nexin-dynein regulatory complex (N-DRC). From these structures, we identify and build atomic models for 30 proteins, including 23 radial-spoke subunits. We reveal how mechanoregulatory complexes dock to doublet microtubules with regular 96-nm periodicity and communicate with one another. Additionally, we observe a direct and dynamically coupled association between RS2 and the dynein motor inner dynein arm subform c (IDAc), providing a molecular basis for the control of motor activity by mechanical signals. These structures advance our understanding of the role of mechanoregulation in defining the ciliary waveform.


Assuntos
Chlamydomonas reinhardtii/anatomia & histologia , Cílios/metabolismo , Locomoção/fisiologia , Proteínas de Plantas/metabolismo , Axonema/metabolismo , Fenômenos Biomecânicos/fisiologia , Microscopia Crioeletrônica , Proteínas do Citoesqueleto/metabolismo , Dineínas/metabolismo , Flagelos/metabolismo , Microtúbulos/metabolismo , Modelos Moleculares , Estrutura Terciária de Proteína , Transdução de Sinais/fisiologia , Nexinas de Classificação/metabolismo
17.
Nat Struct Mol Biol ; 28(1): 20-28, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33318704

RESUMO

Motile cilia power cell locomotion and drive extracellular fluid flow by propagating bending waves from their base to tip. The coordinated bending of cilia requires mechanoregulation by the radial spoke (RS) protein complexes and the microtubule central pair (CP). Despite their importance for ciliary motility across eukaryotes, the molecular function of the RSs is unknown. Here, we reconstituted the Chlamydomonas reinhardtii RS head that abuts the CP and determined its structure using single-particle cryo-EM to 3.1-Å resolution, revealing a flat, negatively charged surface supported by a rigid core of tightly intertwined proteins. Mutations in this core, corresponding to those involved in human ciliopathies, compromised the stability of the recombinant complex, providing a molecular basis for disease. Partially reversing the negative charge on the RS surface impaired motility in C. reinhardtii. We propose that the RS-head architecture is well-suited for mechanoregulation of ciliary beating through physical collisions with the CP.


Assuntos
Chlamydomonas reinhardtii/anatomia & histologia , Cílios/metabolismo , Locomoção/fisiologia , Proteínas de Plantas/metabolismo , Axonema/metabolismo , Microscopia Crioeletrônica , Proteínas do Citoesqueleto/metabolismo , Flagelos/metabolismo , Microtúbulos/metabolismo , Transdução de Sinais/fisiologia
18.
Neuron ; 109(4): 645-662.e9, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33357413

RESUMO

Retinal ganglion cells (RGCs) form an array of feature detectors, which convey visual information to central brain regions. Characterizing RGC diversity is required to understand the logic of the underlying functional segregation. Using single-cell transcriptomics, we systematically classified RGCs in adult and larval zebrafish, thereby identifying marker genes for >30 mature types and several developmental intermediates. We used this dataset to engineer transgenic driver lines, enabling specific experimental access to a subset of RGC types. Expression of one or few transcription factors often predicts dendrite morphologies and axonal projections to specific tectal layers and extratectal targets. In vivo calcium imaging revealed that molecularly defined RGCs exhibit specific functional tuning. Finally, chemogenetic ablation of eomesa+ RGCs, which comprise melanopsin-expressing types with projections to a small subset of central targets, selectively impaired phototaxis. Together, our study establishes a framework for systematically studying the functional architecture of the visual system.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Locomoção/fisiologia , Células Ganglionares da Retina/classificação , Células Ganglionares da Retina/fisiologia , Animais , Animais Geneticamente Modificados , Feminino , Masculino , Estimulação Luminosa/métodos , Peixe-Zebra
19.
J Neurosci Res ; 99(4): 1099-1107, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33368537

RESUMO

The effects of social isolation on an individual's behavior is an important field of research, especially as public health officials encourage social distancing to prevent the spread of pandemic disease. In this study we evaluate the effects of social isolation on physical activity in mice. Utilizing a pixel-based tracking system, we continuously monitored the movement of isolated mice compared with paired cage mates in the home cage environment. We demonstrate that mice that are socially isolated dramatically decrease their movement when separated from their cage mate, and especially in the dark cycle, when mice are normally most active. When isolated mice are re-paired with their original cage mate, this effect is reversed, and mice return to their prior levels of activity. These findings suggest a close link between social isolation and physical activity, and are of particular interest in the wake of coronavirus disease 2019, when many are forced into isolation. Social isolation may affect an individual's overall activity levels in humans too, which may have unintended effects on health that deserve further consideration.


Assuntos
Locomoção/fisiologia , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/psicologia , Isolamento Social/psicologia , Animais , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL
20.
Toxicol Lett ; 339: 23-31, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33359558

RESUMO

Interesterified fat (IF) currently substitutes the hydrogenated vegetable fat (HVF) in processed foods. However, the IF consumption impact on the central nervous system (CNS) has been poorly studied. The current study investigated connections between IF chronic consumption and locomotor impairments in early life period and adulthood of rats and access brain molecular targets related to behavior changes in adulthood offspring. During pregnancy and lactation, female rats received soybean oil (SO) or IF and their male pups received the same maternal supplementation from weaning until adulthood. Pups' motor ability and locomotor activity in adulthood were evaluated. In the adult offspring striatum, dopaminergic targets, glial cell line-derived neurotrophic factor (GDFN) and lipid profile were quantified. Pups from IF supplementation group presented impaired learning concerning complex motor skill and sensorimotor behavior. The same animals showed decreased locomotion in adulthood. Moreover, IF group showed decreased immunoreactivity of all dopaminergic targets evaluated and GDNF, along with important changes in FA composition in striatum. This study shows that the brain modifications induce by IF consumption resulted in impaired motor control in pups and decreased locomotion in adult animals. Other studies about health damages induced by IF consumption may have a contribution from our current outcomes.


Assuntos
Encéfalo/metabolismo , Gorduras na Dieta/efeitos adversos , Locomoção/fisiologia , Atividade Motora/fisiologia , Sistema Nervoso/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ácidos Graxos Trans/efeitos adversos , Fatores Etários , Fenômenos Fisiológicos da Nutrição Animal , Animais , Gorduras na Dieta/metabolismo , Feminino , Humanos , Fenômenos Fisiológicos da Nutrição Materna , Modelos Animais , Fenômenos Fisiológicos do Sistema Nervoso , Gravidez , Ratos , Ácidos Graxos Trans/metabolismo
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