Novel Microglia-based Therapeutic Approaches to Neurodegenerative Disorders / 神经科学通报·英文版

As prominent immune cells in the central nervous system, microglia constantly monitor the environment and provide neuronal protection, which are important functions for maintaining brain homeostasis. In the diseased brain, microglia are crucial mediators of neuroinflammation that regulates a broad spectrum of cellular responses. In this review, we summarize current knowledge on the multifunctional contributions of microglia to homeostasis and their involvement in neurodegeneration. We further provide a comprehensive overview of therapeutic interventions targeting microglia in neurodegenerative diseases. Notably, we propose microglial depletion and subsequent repopulation as promising replacement therapy. Although microglial replacement therapy is still in its infancy, it will likely be a trend in the development of treatments for neurodegenerative diseases due to its versatility and selectivity.

The Structure and Function of Glial Networks: Beyond the Neuronal Connections / 神经科学通报·英文版

Glial cells, consisting of astrocytes, oligodendrocyte lineage cells, and microglia, account for >50% of the total number of cells in the mammalian brain. They play key roles in the modulation of various brain activities under physiological and pathological conditions. Although the typical morphological features and characteristic functions of these cells are well described, the organization of interconnections of the different glial cell populations and their impact on the healthy and diseased brain is not completely understood. Understanding these processes remains a profound challenge. Accumulating evidence suggests that glial cells can form highly complex interconnections with each other. The astroglial network has been well described. Oligodendrocytes and microglia may also contribute to the formation of glial networks under various circumstances. In this review, we discuss the structure and function of glial networks and their pathological relevance to central nervous system diseases. We also highlight opportunities for future research on the glial connectome.

Neuronal GRK2 regulates microglial activation and contributes to electroacupuncture analgesia on inflammatory pain in mice

BACKGROUND: G protein coupled receptor kinase 2 (GRK2) has been demonstrated to play a crucial role in the development of chronic pain. Acupuncture is an alternative therapy widely used for pain management. In this study, we investigated the role of spinal neuronal GRK2 in electroacupuncture (EA) analgesia. METHODS: The mice model of inflammatory pain was built by subcutaneous injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the hind paws. The mechanical allodynia of mice was examined by von Frey test. The mice were subjected to EA treatment (BL60 and ST36 acupuncture points) for 1 week. Overexpression and down-regulation of spinal neuronal GRK2 were achieved by intraspinal injection of adeno associated virus (AAV) containing neuron-specific promoters, and microglial activation and neuroinflammation were evaluated by real-time PCR. RESULTS: Intraplantar injection with CFA in mice induced the decrease of GRK2 and microglial activation along with neuroinflammation in spinal cord. EA treatment increased the spinal GRK2, reduced neuroinflammation, and significantly decreased CFA-induced mechanical allodynia. The effects of EA were markedly weakened by non-cell-specific downregulation of spinal GRK2. Further, intraspinal injection of AAV containing neuron-specific promoters specifically downregulated neuronal GRK2, and weakened the regulatory effect of EA on CFA-induced mechanical allodynia and microglial activation. Meanwhile, overexpression of spinal neuronal GRK2 decreased mechanical allodynia. All these indicated that the neuronal GRK2 mediated microglial activation and neuroinflammation, and subsequently contributed to CFA-induced inflammatory pain. CONCLUSION: The restoration of the spinal GRK2 and subsequent suppression of microglial activation and neuroinflammation might be an important mechanism for EA analgesia. Our findings further suggested that the spinal GRK2, especially neuronal GRK2, might be the potential target for EA analgesia and pain management, and we provided a new experimental basis for the EA treatment of pain.

Absenteísmo-doença no serviço público municipal de Goiânia / Sickness absence in a municipal public service of Goiânia, Brazil

INTRODUÇÃO: O absenteísmo-doença, enquanto falta ao trabalho justificada por licença médica, é um importante indicador das condições de saúde dos trabalhadores. Em geral, características sociodemográficas e ocupacionais situam-se entre os principais fatores associados ao absenteísmo-doença. A administração pública é responsável por 21,8% dos empregos formais no Brasil. Esta população permite o estudo de uma grande variedade de categorias profissionais. OBJETIVO: Analisar o perfil e os indicadores de absenteísmo-doença entre servidores municipais de Goiânia, no Estado de Goiás, Brasil. Métodos: Estudo transversal das licenças certificadas para tratamento de saúde superiores a três dias, de todos os servidores, desde janeiro de 2005 a dezembro de 2010. Foram calculadas as prevalências, utilizando como critérios o número de indivíduos, os episódios e os dias de afastamento. RESULTADOS: Foram concedidas 40.578 licenças certificadas para tratamento de saúde a 13.408 servidores numa população média anual de 17.270 pessoas, o que resultou em 944.722 dias de absenteísmo. A prevalência acumulada de licença no período foi de 143,7%, com média anual de 39,2% e duração de 23 dias por episódio. A prevalência acumulada de absenteísmo-doença foi maior entre mulheres (52,0%) com idade superior a 40 anos (55,9%), com companheiro (49,9%), de baixa escolaridade (54,4%), profissionais de educação (54,7%), > 10 anos de serviço (61,9%) e múltiplos vínculos profissionais (53,7%). Os grupos de diagnósticos (CID-10) com as maiores prevalências acumuladas de licenças foram os do capítulo de transtornos mentais (26,5%), doenças osteomusculares (25,1%) e lesões (23,6%). CONCLUSÕES: Os indicadores de absenteísmo-doença expressam a magnitude desse fenômeno no serviço público e podem auxiliar no planejamento das ações de saúde do trabalhador, priorizando os grupos ocupacionais mais vulneráveis. .

BACKGROUND: Sickness absence, as work absenteeism justified by medical certificate, is an important health status indicator of the employees and, overall, sociodemographic and occupational characteristics are among the main factors associated with sickness absence. Public administration accounts for 21.8% of the formal job positions in Brazil. This population allows the study of a wide range of professional categories. OBJECTIVE: To assess the profile and indicators of sickness absence among public workers from the municipality of Goiania, in the State of Goiás, Brazil. METHODS: A cross-sectional study on certified sick leaves, lasting longer than three days, of all civil servants from January 2005 to December 2010. Prevalence rates were calculated using as main criteria the number of individuals, episodes and sick days. RESULTS: 40,578 certified sick leaves were granted for health treatment among 13,408 public workers, in an annual average population of 17,270 people, which resulted in 944,722 days of absenteeism. The cumulative prevalence of sick leave for the period was of 143.7%, with annual average of 39.2% and duration of 23 days per episode. The cumulative prevalence of sickness absence was higher among women (52.0%), older than 40 years old (55.9%), with a partner (49.9%), low schooling (54.4%), education professionals (54.7%), > 10 years of service (61.9%), and with multiple work contracts (53.7%). Diagnoses groups (ICD-10) with higher cumulative prevalence of sick leaves were those with mental disorders (26.5%), musculoskeletal diseases (25.1%), and injuries (23.6%). CONCLUSIONS: Indicators of sickness absence express the magnitude of this phenomenon in the public sector and can assist in planning health actions for the worker, prioritizing the most vulnerable occupational groups. .

Neurobiología de la glía y sus funciones en el desarrrollo, la fisiología y la patología del SNC / The neurobiology of glial cells and the function they perform in the development, physiology and the pathology of the Central Nervous System (CNS)

Las células gliales presentan una función similar a sus homólogos más excitables del sistema nervioso central (SNC), las neuronas. Dentro del sistema nervioso en desarrollo, los astrocitos y células de Schwann ayudan activamente a promover la formación de sinapsis y la función, e incluso han sido implicados en la eliminación de sinapsis. En el cerebro adulto, los astrocitos responden a la actividad sináptica por la liberación de los transmisores que modulan esta actividad. De esta forma, las células gliales son participantes activos en la función cerebral. Investigaciones recientes han cambiado la percepción de la glía, que además de ser células de apoyo y soporte para las neuronas, son socios dinámicos que participan en el metabolismo del cerebro y la comunicación entre las neuronas. El descubrimiento de nuevas funciones gliales coincide con los estudiois crecientes de la participación de la glía en las enfermedades cerebrales más comunes, como el traumatismo craneoencefálico, el accidente cerebrovascular, la lesión de la médula espinal, la esclerosis múltimple, la epilepsia, la enfermedad de Alzheimer, la enfermedad de Parkinson, la esclerosis lateral amiótica, el síndrome de Down, el glioma, el trastorno depresivo mayor y el autismo. Sin embargo, quedan muchas preguntas sobre la identidad de la glía y su importancia.

Glial cells have a function similar to their counterparts more excitable central nervous system (CNS), neurons. Within the developing nervous system, astrocytes and Schwann cells actively help to promote synapse formation and function, and have even been involved in the elimination of synapses. In the adulto brain, the astrocytes respond to synaptic activity by realeasing transmitters that modulate synaptic activity. Thus, glia are active participants in brain function. Recent reserch has changed the perception of glia, in addition to help and support cells to neurons, are also dynamic partners participating in brain metabolism and communication between neurons. The discovery fo new glial functions coincides with growing studies of the involvement of glia in brain diseases are the most common head injury, stroke, injury to the spinal cord, multiple sclerosis, epilepsy. Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Down's syndrome, glioma, mayor depressive disorder and autism. Many questions remain about the identity of the glial and importance.

Dolor agudo postoperatorio: cómo el proceso quirúrgico induce neuroplasticidad / Accute postoperative pain: how the surgical process leads to neuroplasticity

El dolor agudo postoperatorio constituye un importante desafío para el anestesiólogo y un derecho para los pacientes. No obstante, en la actualidad éste continúa presente en un alto porcentaje de pacientes, a pesar de los esfuerzoz en la difusión de su evaluación y en el uso de diferentes terapias. una importante e interesante forma de cambiar estas cifras puede ser la investigación de la fisiopatología del dolor agudo postoperatorio y la difusión de los resultados. En los últimos años se ha profundizado en el conocimiento de la fisiopatología del dolor agudo postoperatorio, donde se ha determinado que existen cambios capaces de enfrentar la noxa quirúrgica, conocidos como neuroplasticidad, una de cuyas principales expresiones es el mecanismo de sensibilización. Se presenta a continuación una revisión de los principales mecanismos involucrados en el desarrollo y mantención de esta neuroplasticidad.

Accute postoperative pain is a great challenge for anesthesiologists and a right for patients. However, there is still an important percentage of patients with accute postoperative pain, despite all the efforts that have been made to divulge the existing evaluation methods and the use of different therapies. Research of physiopathology of accute postoperative pain might be a relevant and interesting way to change such percentage as well as the publication of the results from that research. In the last years, researchers have gained deeper knowledge in the field of physiopathology of accute postoperative pain and found there are some changes with the capacity to face the surgical noxa known as neuroplasticity, being one of the most important expressions the sensitizazation mechanism. A review of the most important mechanisms that play a part in the development and maintenance of this neuroplasticity is presented below.

Influence of NF-kappa B on the development and regulation of neural system / 法医学杂志

Nuclear factor-kappa B (NF-kappa B) plays an important role in controlling infection, immunity responses, cellar differentiation and apoptosis. It is of characteristics especially in neural system. NF-kappa B exist widely in neural cells and transfer from plasma into nucleolus through diversified activation passages. in addition, NF-kappa B is also a key factor in the development of the neural system, anti-apoptosis and modulating the activity of glia cells. It is of great significance in the forensic science.

Entry, dispersion and differentiation of microglia in the developing central nervous system

Microglial cells within the developing central nervous system (CNS) originate from mesodermic precursors of hematopoietic lineage that enter the nervous parenchyma from the meninges, ventricular space and/or blood stream. Once in the nervous parenchyma, microglial cells increase in number and disperse throughtout the CNS; these cells finally differentiate to become fully ramified microglial cells. In this article we review present knowledge on these phases of microglial development and the factors that probably influence them.

Proliferation of differentiated glial cells in the brain stem

Classical studies of macroglial proliferation in muride rodents have provided conflicting evidence concerning the proliferating capabilities of oligodendrocytes and microglia. Furthermore, little information has been obtained in other mammalian orders and very little is known about glial cell proliferation and differentiation in the subclass Metatheria although valuable knowledge may be obtained from the protracted period of central nervous system maturation in these forms. Thus, we have studied the proliferative capacity of phenotypically identified brain stem oligodendrocytes by tritiated thymidine radioautography and have compared it with known features of oligodentroglial differentation as well as with proliferation of microglia in the opossum Didelphis marsupialis. We have detected a previously undescribed ephemeral, regionally heterogenous proliferation of oligodendrocytes expressing the actin-binding, ensheathment-related protein 2' 3'- cyclic nucleotide 3' -phosphodiesterase (CNPase), that is not necessarily related to the known regional and temporal heterogeneity of expression of CNPase in cell bodies. On the other hand, proliferation of microglia tagged by the binding of Griffonia simplicifolia B4 isolectin, which recognizes an alpha-D-galactosyl-bearing glycoprotein of the plasma membrane of macrophages/microglia, is known to be long lasting, showing no regional heterogeneity and being found amongst both ameboid and differentiated ramified cells, although at different rates. The functional significance of the proliferative behavior of these differentiated cells is unknown but may provide a lowgrade cell renewal in the normal brain and may be augmented under pathological conditions.

Funçöes da neuroglia no sistema nervoso central: contribuiçäo para a plasticidade neural / Neuroglia functions in the central nervous system: contribution to the neural plasticity

Apesar da existência de inúmeros fatores inibitórios interferindo na capacidade adaptativa às interferências do meio ambiente, o sistema nervoso central possui capacidade de reorganizaçÒo e regeneraçÒo axonal. A investigaçäo da contribuiçäo das células da glia para o processo de plasticidade neural tem resultado em um crescente número de estudos os quais apontam o envolvimento destas células após injúrias, patologias degenerativas ou na aprendizagem. Estas evidências surgem com a constataçäo da ocorrência de gliose nas diferentes condiçöes acima. Fundamentada na revisÒo de trabalhos que demonstram, por meio de modelos experimentais e em patologias, a participaçÒo da glia, o presente trabalho analisa e descreve a participaçäo das células da glia na fisiologia cerebral. A resposta reativa da glia está associada à síntese de fatores de crescimento, neurotransmissores e citocininas. Desta forma, pode ser trófica e contribuir para a manutençäo da funçäo neural, ou tóxica, e resultar em morte neuronal. O resultado final dependerá do equilíbrio entre seus produtos de secreçäo e da capacidade de manutençäo da homeostase iônica. Considera-se, assim, que as células da glia atuam em mecanismos fundamentais que caracterizam a capacidade de reorganizaçäo e recuperaçÒo neural.