Total rupture of Achilles tendon induces inflammatory response and glial activation on the spinal cord of mice

Rupture of Achilles tendon is a common accident affecting professional and recreational athletes. Acute and chronic pain are symptoms commonly observed in patients with rupture. However, few studies have investigated whether Achilles tendon rupture is able to promote disorders in the central nervous system (CNS). Therefore, the current study aimed to evaluate nociceptive alterations and inflammatory response in the L5 lumbar segment of Balb/c mice spinal cord after Achilles tendon rupture. We found increased algesia in the paw of the ruptured group on the 7th and 14th days post-tenotomy compared with the control group. This phenomenon was accompanied by overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase-2 (NOS-2) as well as hyperactivation of astrocytes and microglia in nociceptive areas of L5 spinal cord as evidenced by intense GFAP and IBA-1 immunostaining, respectively. Biochemical studies also demonstrated increased levels of nitrite in the L5 spinal cord of tenotomized animals compared with the control group. Thus, we have demonstrated for the first time that total rupture of the Achilles tendon induced inflammatory response and nitrergic and glial activation in the CNS in the L5 spinal cord region.

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.

Roles of NG2 Glia in Cerebral Small Vessel Disease / 神经科学通报·英文版

Cerebral small vessel disease (CSVD) is one of the most prevalent pathologic processes affecting 5% of people over 50 years of age and contributing to 45% of dementia cases. Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion, impaired cerebral vascular reactivity, and leakage of the blood-brain barrier in CSVD. However, the pathogenesis of CSVD remains elusive thus far, and no radical treatment has been developed. NG2 glia, also known as oligodendrocyte precursor cells, are the fourth type of glial cell in addition to astrocytes, microglia, and oligodendrocytes in the mammalian central nervous system. Many novel functions for NG2 glia in physiological and pathological states have recently been revealed. In this review, we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

Astrocytes in Chronic Pain: Cellular and Molecular Mechanisms / 神经科学通报·英文版

Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of therapies. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions, including chronic pain. Astrocytes regulate nociceptive synaptic transmission and network function via neuron-glia and glia-glia interactions to exaggerate pain signals under chronic pain conditions. It is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic pain. Therefore, this review presents our current understanding of the roles of astrocytes in chronic pain, how they regulate nociceptive responses, and their cellular and molecular mechanisms of action.

A Young Woman with Leukoencephalopathy and Significant Corpus Callosum Atrophy / 罕见病研究

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare autosomal-dominant progressive leukodystrophy, caused by mutations of colony stimulating factor-1 receptor (CSF1R) gene. Age of onset is usually between 40 and 50 years old and the clinical presentations include dementia, apraxia, behavioral changes, pyramidal and extrapyramidal signs. Varying clinical manifestations have led to misdiagnoses. Magnetic resonance imaging (MRI) typically reveals white matter changes with T2-Flair/DWI hyperintensity and atrophy especially for thinning of the corpus callosum. Here, we report a young woman experiencing hypomnesia for 2 years with lower extremities weakness and rigidity for 1 month. Considering the evidence of clinical manifestations, imaging and genetic test, this patient was diagnosed with ALSP.

Biomarcadores gliais da doença de Alzheimer / Glial biomarkers of Alzheimer's disease

Introdução: A neuroinflamação associada às células gliais é um elemento importante do processo patológico da doença de Alzheimer (DA). Este estudo apresenta uma revisão dos marcadores gliais quitinase 3-like 1 (YKL-40), do receptor desencadeado expresso nas células mieloides 2 (Triggering receptor expressed on myeloid cells 2 ­ TREM2), da proteína acídica fibrilar glial (GFAP) e da proteína B S100 ligante de cálcio (S100B). Métodos: Nesta revisão são analisados os marcadores gliais YKL-40, TREM2, GFAP e S100B presentes em sangue e/ou líquido cefalorraquidiano (LCR), a partir de estudos publicados até 2020 nos bancos de dados do PubMed, Medline e Periódicos Capes. Resultados: Foram recuperados 233 documentos, dentre os quais foram incluídos 60. Todos os marcadores se encontram aumentados na DA em LCR ­ YKL-40 e TREM2 solúvel (sTREM2), já na fase pré-clínica ­, e em sangue, e estão correlacionados ao declínio cognitivo. No entanto, nenhum dos marcadores analisados apresentou grande potencial para o diagnóstico diferencial. Além da proteína TREM2 solúvel no LCR, no sangue também se pode identificar alteração nos níveis do RNAm de TREM2. GFAP sanguíneo mostra ser o melhor em distinguir controles de pacientes com Alzheimer. Há evidências de um efeito protetivo da ativação glial em reação ao acúmulo amiloide. Conclusão: Os marcadores gliais no geral têm pouca utilidade para o diagnóstico diferencial, mas podem auxiliar no prognóstico e como biomarcadores inespecíficos para doenças neurodegenerativas. (AU)

Introduction: Glial cell-associated neuroinflammation is a driving force for the pathological process of Alzheimer's disease (AD). This study is a systematic review aimed to analyze the following glial markers: chitinase-3-like protein 1 (YKL-40), triggering receptor expressed on myeloid cells 2 (TREM2), glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B). Methods: The PubMed, MEDLINE and CAPES Journals databases were searched for studies published until 2020 that addressed blood and/or cerebrospinal fluid (CSF) levels of YKL-40, TREM2, GFAP and S100B. Results: A total of 233 articles were retrieved, of which 60 were included in this study. All CSF ­ YKL-40 and soluble TREM2 (sTREM2) in preclinical stage ­ and blood biomarker levels were elevated for AD and were correlated to cognitive decline. None of the analyzed biomarkers showed promising results for differential diagnosis. Besides CSF sTREM2 levels, blood TREM2 mRNA levels were also altered in AD. Blood GFAP levels seem to be the best option for distinguishing controls from AD patients.' There is evidence of a protective role of glial activation in amyloid accumulation. Conclusion: Glial markers in general are of little use for differential diagnosis but can assist in prognosis and as nonspecific biomarkers of neurodegenerative diseases. (AU)

Glioblastoma de células gigantes: informe de un caso / Giant cell glioblastoma: case report

Antecedentes: El Glioblastoma (GB) o astrocitoma grado IV, es un tumor agresivo que se origina de células gliales, con alto grado de malignidad, prevalencia menor al 1% en fosa posterior e incidencia menor al 0.5% de todos los GB. Actualmente se describen alrededor de 75 casos a nivel mundial. Descripción del caso clínico: Femenina, 24 años, referida a emergencia de Neurocirugía del Hospital Escuela Universitario, presentó cefalea holocraneana intensa, vómitos, náuseas, visión borrosa, vértigo y anorexia. Al examen neurológico mostró discreta adiadococinesia derecha y signos de papiledema. La tomografía axial computarizada cerebral evidenció lesión heterogénea en vermis extendido a hemisferio cerebeloso derecho, por lo que se realizó craniectomía suboccipital, abordaje transcerebelar, con citorreducción tumoral, encontrando masa vascularizada con componente quístico. Estudio anatomopatológico evidenció glioblastoma multiforme variante de células gigantes, confirmado con tinción de inmunohistoquímica (PFGA, CD34+ y vimentina). Paciente con buena evolución clínica postquirúrgica, egresada sin déficit neurológico. 16 meses después, presentó síndrome de recidiva tumoral y complicaciones, por lo que se reintervino en 4 ocasiones, posterior a recibir 30 dosis de radioterapia y 12 ciclos de quimioterapia, se reingresó con deterioro neurológico progresivo, signos meníngeos y síndrome de Parinaud, escala de Karnofsky (30 puntos), realizándose derivación ventrículo-peritoneal por compresión del IV ventrículo e hidrocefalia obstructiva secundaria, luego desarrolló neumonía intrahospitalaria, falleciendo a las dos semanas. Conclusiones: Es importante identificar la variante biológica del glioblastoma de forma temprana, para determinar pronóstico y acciones terapéuticas que influirán en la calidad de vida, así como la supervivencia...(AU)

Glia maturation factor-gamma inhibits the proliferation of human colorectal cancer LoVo cells and affects the cytoskeletal motion of human umbilical vein endothelial cells / 中国组织工程研究

BACKGROUND: Glial maturation factor-gamma (GMFG) is one of the members of the ADF/cofilin superfamily protein in the process of cytoskeleton remodeling. It can regulate the cell movement by regulating actin-mediated cytoskeleton reorganization. The authors previously found that the high expression of GMFG is associated with the clinicopathological features of colorectal cancer patients, but the specific upstream and downstream mechanisms need to be explored. OBJECTIVE: To study the effects of GMFG on cytoskeleton and LoVo cell proliferation. METHODS: (1) Human umbilical vein endothelial cells were inoculated in a laser confocal dish. After the cells grew stably, the correlation between the expression of GMFG and the expression of cytoskeletal protein F-actin was observed by immunofluorescence staining. Colchicine inhibited mitosis. The cells were divided into control group, 0.5 mg/L colchicine group and 1.0 mg/L colchicine group. The cell cycle was observed by flow cytometry and GMFG protein expression was observed by western blot assay. (2) Human colorectal cancer LoVo cells were inoculated in a laser confocal dish. After the cells grew stably, the correlation between GMFG expression and cell cycle was observed by immunofluorescence staining. Afterwards, siRNA was used to interfere the expression of GMFG in LoVo cells. The LoVo cells were divided into blank control group, empty transfer group and siRNA-GMFG group. The cell proliferation rate was detected by Edu assay. RESULTS AND CONCLUSION: (1) In human umbilical vein endothelial cells, the expression of GMFG was associated with the cytoskeletal motion of human umbilical vein endothelial cells, and the expression of GMFG increased when the cytoskeleton retracted. After colchicine inhibited the mitosis of human umbilical vein endothelial cells, the proportion of cells in G2/M phase increased and the expression of GMFG protein decreased with the increase of colchicine dosage. (2) In LoVo cells, the expression intensity of GMFG was associated with mitosis, and the expression of GMFG was enhanced in the middle and late stages of cell mitosis. (3) After siRNA interference with GMFG in LoVo cells, the cell proliferation rate was decreased. (4) Results verify that interference with GMFG can inhibit the proliferation rate of LoVo cells of human colorectal cancer, and there is a certain correlation between cytoskeletal motion and GMFG expression.

A platform to understand amyotrophic lateral sclerosis (ALS) and extend human motor neurons longevity / Plataforma para empezar a comprender la esclerosis lateral amiotrófica (ELA) y extender la longevidad de neuronas motoras humanas

In vitro modeling of neurodegenerative diseases is now possible by using patient-derived induced pluripotent stem cells (iPS). Through them, it is nowadays conceivable to obtain human neurons and glia, and study diseases cellular and molecular mechanisms, an attribute that was previously unavailable to any human condition. Amyotrophic lateral sclerosis (ALS) is one of the diseases that has gained a rapid advance with iPS technology. By differentiating motor neurons from iPS cells of ALS- patients, we are studying the mechanisms underlying ALS- disease onset and progression. Here, we introduce a cellular platform to help maintain longevity of ALS iPS-motor neurons, a cellular feature relevant for most late-onset human diseases. Long term cultures of patient-derived iPS cells might prove to be critical for the development of personalized-drugs.

Actualmente es posible modelar in vitro enfermedades neurodegenerativas humanas mediante el uso de células madre pluripotentes inducidas (iPS) derivadas del paciente. A través de ellas, es hoy concebible obtener neuronas y glía humanas, y estudiar mecanismos celulares y moleculares de enfermedades, un atributo que anteriormente no era posible para ninguna condición humana. La esclerosis lateral amiotrófica (ELA) es una de las enfermedades que se ha beneficiado con la tecnología de iPS. Al diferenciar neuronas motoras de células iPS obtenidas de pacientes con ELA, hemos iniciado estudios sobre los mecanismos que subyacen a la aparición y progresión de la enfermedad. Aquí, presentamos el desarrollo de una plataforma celular que permite extender la longevidad de las neuronas motoras derivadas de iPS, una característica relevante para la mayoría de las enfermedades humanas de inicio tardío. Los cultivos a largo plazo de células iPS provenientes de pacientes pueden ser determinantes en el desarrollo de terapias asociadas a la medicina de precisión.

Envolvimento das células da glia na ação antinociceptiva da toxina phα1ß e da ω-conotoxina mviia na dor inflamatória periférica / Involvement of glial cells in the antinociceptive action of phα1ß toxin and ω-conotoxin mviia in peripheral inflammatory pain

A lesão inflamatória de origem periférica aumenta a sensibilidade sensória a um estímulo mecânico de leve intensidade, provocando dor, um processo conhecido como alodinia. A recente descoberta de que astrócitos e micróglia da medula espinal tornam-se reativos devido à inflamação periférica, sugere que a glia deve estar envolvida na manifestação patológica da dor. Nesta tese, observou-se que a inflamação periférica, induzida pela injeção intraplantar do adjuvante completo de Freund (CFA), causa alodinia mecânica assim como mudanças na glia. Dentre essas mudanças destacamos o aumento de marcadores específicos da glia, aumento da proliferação de astrócitos assim como alterações morfológicas na micróglia, todas elas características do fenótipo reativo da glia. Além disso, este estudo descobriu que a injeção intratecal da toxina de aranha Phα1ß, um peptídeo com ação analgésica que bloqueia canais de cálcio dependente de voltagem (VGCC), reverte todas as alterações da glia da medula espinal causadas pela inflamação periférica. Essas observações, em resumo, sugerem que a toxina Phα1ß, além de sua já reconhecida ação analgésica, também possui efeitos anti-inflamatórios sobre a plasticidade glial.

A peripheral inflammatory injury increases the mechanical sensitivity in response to light-touch, also named as allodynia. The discovery that spinal astrocytes and microglia become reactive to the peripheral inflammation suggests that the glia presumably engage with the pain pathophysiology. Here, we found that the peripheral inflammation induced by intraplantar injection of complete Freund's adjuvant (CFA) produce mechanical allodynia and robust changes in the spinal glial. Among these changes we found an increase of specific glial markers, increment of astrocytes proliferation, elevation of microglia density and morphologic changes, all of them compatible with the glia reactive phenotype. Moreover, we found that intrathecal injection with the analgesic Phα1ß spider toxin, a voltage-gated calcium channel (VGCC) blocker, reverses all the glial pathological features of the peripheral inflammation. We therefore suggest that the Phα1ß toxin, apart from its notable analgesic effects, is also a potent anti-inflammatory compound acting on glial plasticity.

Efeitos da exposição à fumaça do cigarro e suas implicações na neuroinflamação / Effects of exposure to cigarette smoke and its implications on neuroinflammation

O Sistema Nervoso Central (SNC) humano é formado por cerca de 86,1 bilhões de neurônios entre o encéfalo e a medula espinhal. O desenvolvimento pré-natal humano (tempo da concepção ao nascimento) possui cerca de 38 semanas, e é dividido na fase embrionária que corresponde ao período das 8 semanas iniciais da gestação, seguido pela fase fetal. A fase embrionária é o período mais vulnerável à ocorrência de anormalidades congênitas. Por ser um órgão com grande período de desenvolvimento, o SNC está sujeito às alterações genéticas, epigenéticas e ambientais. Durante a fase de implantação do embrião, o DNA é mais vulnerável às influências externas, como à fumaça do cigarro, aumentando o risco de retardo do desenvolvimento fetal, o risco de morte súbita pós-natal e de anormalidades do sistema imune. Neste contexto, o objetivo deste trabalho é avaliar os efeitos da exposição à fumaça do cigarro sobre o processo de neuroinflamação da prole de camundongos C57BL/6 expostos à fumaça do cigarro durante a gestação e desafiados ou não com LPS. Para tanto, camundongos C57BL/6 fêmeas prenhes foram expostas à fumaça do cigarro desde o plug vaginal até o nascimento da prole. No 3º dia de vida, os filhotes foram separados para três linhas de trabalho: 1) in vivo: os animais foram desafiados com LPS pelo período de 4h, seguidos de eutanasia e análises de PCR Array do SNC. 2) in vitro: os encéfalos dissecados foram utilizados para a preparação de cultura mista de glia e da cultura enriquecida com neurônio. Após a maturação celular, as células foram estimuladas com LPS 100 ng/mL e, após 24h, foram realizados ensaios de CBA, citometria de fluxo, PCR, dosagem de NO, avaliação de morte celular e metilação global. 3) Encefalomielite Autoimune Experimental (EAE): após o desmame, os animais foram mantidos em suas caixas moradia por 8 semanas sem nenhum estímulo externo, e então foram imunizados com MOG35-55 para o desenvolvimento da EAE. Nos experimentos in vivo observamos o aumento da transcrição de genes relacionados ao processo inflamatório, como interleucinas e quimiocinas. Em relação aos experimentos in vitro observamos maior crescimento de células astrocitárias (astrogliose), e células da microglia com aumento de moléculas co-estimuladoras (CD80 e CD86) bem como da transcrição e concentração de citocinas pró-inflamatórias e produção de NO. Em cultura enriquecida de neurônio, foi observado aumento na porcentagem de células em apoptose no grupo exposto à fumaça do cigarro desafiados ou não com LPS. O bloqueio da atividade da microglia pela minociclina reverteu a apoptose e diminuiu a produção de NO minimizando a morte celular. Em relação aos experimentos de EAE, os animais expostos à fumaça do cigarro no período gestacional, quando imunizados na vida adulta apresentam aumento no grau da doença bem como maior persistência da mesma quando observado escore clínico, além de acompanhados de um grau maior de infiltrado celular e desmielinização. Desta forma podemos concluir que a exposição à fumaça do cigarro durante o período gestacional leva a uma programação fetal com aumento da resposta neuroinflamatória frente a um estimulo sistêmico, trazendo consequências na vida adulta

The human central nervous system (CNS) is made up of about 86.1 billion neurons between the brain and the spinal cord. The human prenatal development (time from conception to birth) is about 38 weeks, and is divided into the embryonic phase that corresponds to the period of the initial 8 weeks of gestation, followed by the fetal phase. The embryonic stage is the period most vulnerable to the occurrence of congenital abnormalities. Because it is an organ with a long period of development, the CNS is subject to genetic, epigenetic and environmental changes. During the embryo implantation phase, DNA is more vulnerable to external influences such as cigarette smoke, increasing the risk of delay on fetal development, risk of sudden postnatal death, and abnormalities of the immune system. In this context, the aim of this work is to evaluate the effects of exposure to cigarette smoke on the neuroinflammation process of offspring of C57BL/6 mice exposed to cigarette smoke during gestation and challenged or not with LPS. For this, pregnant female C57BL/6 mice were exposed to cigarette smoke from vaginal plug to offspring birth. On the 3rd day of life the offspring were separated into three lines of work: 1) in vivo: the animals were challenged with 1mg/Kg LPS and after 4h they followed to euthanasia; PCR analysis of the CNS was made in this period. 2) in vitro: dissected encephalons were used for the preparation of mixed culture of glia and the culture enriched with neuron. After cell maturation, the cells were stimulated with 100 ng/mL LPS and, after 24 hours, CBA, flow cytometry, PCR, NO assay, cell death and global methylation assays were performed. 3) Experimental Autoimmune Encephalomyelitis (EAE): After weaning, the animals were kept in their housing for 8 weeks without any external stimulus, and then were immunized with MOG35-55 for the development of EAE. In the in vivo experiments we observed increased transcription of genes related to the inflammatory process, such as interleukins and chemokines. In vitro experiments showed higher growth of astrocytes (astrogliosis) and microglia cells with increased stimulatory molecules (CD80 and CD86) as well as the transcription and concentration of proinflammatory cytokines and NO production. In the enriched neuron culture, an increase in the percentage of cells in apoptosis was observed in the group exposed to cigarette smoke challenged or not with LPS. Blocking microglial activity by minocycline reversed apoptosis and decreased NO production by minimizing cell death. The EAE experiments shows that the animals exposed to cigarette smoke in the gestational period, when immunized in adulthood, present an increase in the degree of the disease as well as a greater persistence of the disease; The higher as the clinical score higher is the degree of cellular infiltration and demyelination. In this way we can conclude that the exposure to cigarette smoke during the gestational period leads to a fetal programming with increased neuroinflammatory response to a systemic stimulus and that this is able to last until the adult stage

Advances of Nogo-A protein in the mechanism of epilepsy / 中华神经科杂志

The myelin-associated protein Nogo-A was considered to be the axon growth inhibitory factor, which participates in a variety of pathophysiological regulation of nervous system. In recent years, a growing number of studies have shown that Nogo-A protein is closely related to epilepsy by regulating dendritic plasticity, mediating abnormal nerve migration and regulating glial cell activation, etc. This article will review the research progress of Nogo-A in epilepsy in recent years.

H3K27me3 Signal in the Cis Regulatory Elements Reveals the Differentiation Potential of Progenitors During Drosophila Neuroglial Development / 基因组蛋白质组与生物信息学报·英文版

Drosophila neural development undergoes extensive chromatin remodeling and precise epigenetic regulation. However, the roles of chromatin remodeling in establishment and maintenance of cell identity during cell fate transition remain enigmatic. Here, we compared the changes in gene expression, as well as the dynamics of nucleosome positioning and key histone modifications between the four major neural cell types during Drosophila neural development. We find that the neural progenitors can be separated from the terminally differentiated cells based on their gene expression profiles, whereas nucleosome distribution in the flanking regions of transcription start sites fails to identify the relationships between the progenitors and the differentiated cells. H3K27me3 signal in promoters and enhancers can not only distinguish the progenitors from the differentiated cells but also identify the differentiation path of the neural stem cells (NSCs) to the intermediate progenitor cells to the glial cells. In contrast, H3K9ac signal fails to identify the differentiation path, although it activates distinct sets of genes with neuron-specific and glia-related functions during the differentiation of the NSCs into neurons and glia, respectively. Together, our study provides novel insights into the crucial roles of chromatin remodeling in determining cell type during Drosophila neural development.

Axon Guidance Molecules Guiding Neuroinflammation

Axon guidance molecules (AGMs), such as Netrins, Semaphorins, and Ephrins, have long been known to regulate axonal growth in the developing nervous system. Interestingly, the chemotactic properties of AGMs are also important in the postnatal period, such as in the regulation of immune and inflammatory responses. In particular, AGMs play pivotal roles in inflammation of the nervous system, by either stimulating or inhibiting inflammatory responses, depending on specific ligand-receptor combinations. Understanding such regulatory functions of AGMs in neuroinflammation may allow finding new molecular targets to treat neurodegenerative diseases, in which neuroinflammation underlies aetiology and progression.

Role of Agmatine on Neuroglia in Central Nervous System Injury

Recovery from central nervous system (CNS) injury, such as stroke or spinal cord injury (SCI), largely depends on axonal regeneration, and the neuronal and glial cells plasticity in the lesioned tissue. The lesioned tissue following CNS injury forms a scar that is composed of astrocytes and mixed with connective tissues. At the glial scar, the regenerating axon forms dystrophic endbulbs which do not regenerate and grow beyond the glial scar without a suitable environment. Along with the astrocytes, microglia are also suspected of being involved in necrotic and apoptotic neuronal cell death and the early response to axonal damage in CNS injury. The inflammatory response, a major component of secondary injury and controlled by the microglia, plays a pivotal role in nerve injury and control the regenerative response. As a result, it is very important to control the glial cell function in order to assure the recovery of the CNS injury. Studies have suggested that agmatine, a L-arginine derived primary amine, is a potential modulator of glial cell function after CNS injuries. Agmatine was found to possess anti-inflammatory and neuroprotective characteristics that benefited the rehabilitation process following CNS injury. In this review, we will discuss the effect of agmatine on glial cells in the process of recovery after CNS injury.

Effects of intrathecal injection of SOCS3 on pain behavior and expression of proinflammatory cyto-kines in mice with neuropathic pain / 中华行为医学与脑科学杂志

Objective To evaluate the role of suppressor of cytokine signaling 3 ( SOCS3) in the spinal cord of chronic sciatic constriction injury ( CCI) mice. Methods Part one:four Kunming mice were selected to receive the CCI operation by sciatic nerve ligation. Seven days after operation the mice were sac-rificed and L4～6 segments of the spinal cord were removed. The co-expression of SOCS3 with NeuN ( for neurons),GFAP (for astrocytes),or IBA1 (for microglia) in spinal were detected by immunohistofluores-cence. Part two:thirty-two Kunming mice were divided into 4 groups according to random number table:sham operation group (group SH),CCI group (group BP),CCI+Lenti-SOCS3 group (group BS),CCI +Lenti-vector group (group BV). Group BS were intrathcal injected of Lenti-SOCS3 (2 μl) and group BV were intrathcal injected of Lenti-vector (2 μl) on 7 d,8 d,9 d after operation. Paw withdrawal latency ( PWL) and paw withdrawal threshold ( PWT) were measured at 1 d before operation and 5,7,10,12,14 d after operation. Mice were then sacrificed and L4～6 segments of the spinal cord were removed for determina-tion of GFAP,IBA-1 by Western blot and IL-6,IL-1β,TNF-α by Elisa on 14 d. Results SOCS3 was dis-tributed in dorsal horn,and expressed in astrocytes and microglia,but hardly colocalized with neurons. Com-pared with group SH,the PWL and PWT of group BP and BV were significantly decreased after operation (all P<0. 05),and the expression of GFAP,IBA-1,IL-6,IL-1β and TNF-α was significantly increased (all P<0. 05). Compared with group BV,the PWL (5. 1±0. 9,7. 5±0. 8,7. 2±1. 4) and PWT (6. 1±1. 4,8. 9± 1. 1,8. 2±2. 1) of group BS was significantly increased on 10,12,14 d (all P<0. 05),and the expression of GFAP (1. 69±0. 45),IBA-1(1. 76±0. 25),IL-6 (181±8),IL-1β (151±7),TNF-α (216±9) was signifi-cantly downregulated (P<0. 05) . Conclusion SOCS3 alleviates neuropathic pain by inhibiting the glial ac-tivation and the expression of proinflammatory cytokines IL-6,IL-1β,TNF-α.

Astrocytes, Microglia, and Parkinson's Disease

Astrocytes and microglia support well-being and well-function of the brain through diverse functions in both intact and injured brain. For example, astrocytes maintain homeostasis of microenvironment of the brain through up-taking ions and neurotransmitters, and provide growth factors and metabolites for neurons, etc. Microglia keep surveying surroundings, and remove abnormal synapses or respond to injury by isolating injury sites and expressing inflammatory cytokines. Therefore, their loss and/or functional alteration may be directly linked to brain diseases. Since Parkinson's disease (PD)-related genes are expressed in astrocytes and microglia, mutations of these genes may alter the functions of these cells, thereby contributing to disease onset and progression. Here, we review the roles of astrocytes and microglia in intact and injured brain, and discuss how PD genes regulate their functions.

Inflammatory Changes in Paravertebral Sympathetic Ganglia in Two Rat Pain Models / 神经科学通报·英文版

Injury to peripheral nerves can lead to neuropathic pain, along with well-studied effects on sensory neurons, including hyperexcitability, abnormal spontaneous activity, and neuroinflammation in the sensory ganglia. Neuropathic pain can be enhanced by sympathetic activity. Peripheral nerve injury may also damage sympathetic axons or expose them to an inflammatory environment. In this study, we examined the lumbar sympathetic ganglion responses to two rat pain models: ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion (DRG), which does not involve axotomy. Both models resulted in neuroinflammatory changes in the sympathetic ganglia, as indicated by macrophage responses, satellite glia activation, and increased numbers of T cells, along with very modest increases in sympathetic neuron excitability (but not spontaneous activity) measured in ex vivo recordings. The spinal nerve ligation model generally caused larger responses than DRG inflammation. Plasticity of the sympathetic system should be recognized in studies of sympathetic effects on pain.

Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders

Objective: To investigate plasma concentrations of S100B (a calcium-binding protein derived primarily from the glia) and inflammatory cytokines in children with autism and the relationship between S100B and cytokine concentrations. Methods: Plasma levels of S100B, tumor necrosis factor alpha (TNF-α), interferon gamma, interleukin (IL)-1β, IL-4, IL-6, IL-10, and IL-17A were measured in 40 unmedicated children with autism and 35 normally developing healthy children. The severity of autism was assessed using the Childhood Autism Rating Scale (CARS). Results: Concentrations of both S100B and TNF-α were higher in children with autism before and after adjusting for a priori-selected confounders (age, sex, and body mass index). S100B concentrations were higher in children with severe autism compared to children with mild-moderate autism. However, this association remained as a trend after adjusting for confounders. S100B concentrations correlated positively with TNF-α concentrations. Conclusion: Our findings showing an increase in peripheral concentrations of S100B and TNF-α provide limited support to the hypothesis about the roles of altered immune function and S100B in autism spectrum disorder (ASD). Studies of larger numbers of well-characterized individuals with ASD are needed to clarify the potential role of the immune system in the pathophysiology of this disorder.

Decreased Glial GABA and Tonic Inhibition in Cerebellum of Mouse Model for Attention-Deficit/Hyperactivity Disorder (ADHD)

About 5~12% of school-aged children suffer from the Attention-Deficit/Hyperactivity Disorder (ADHD). However, the core mechanism of ADHD remains unclear. G protein-coupled receptor kinase-interacting protein-1 (GIT1) has recently been reported to be associated with ADHD in human and the genetic deletion of GIT1 result in ADHD-like behaviors in mice. Mice lacking GIT1 shows a shift in neuronal excitation/inhibition (E/I) balance. However, the pricise mechanism for E/I imbalance and the role of neuron-glia interaction in GIT1 knockout (KO) mice have not been studied. Especially, a possible contribution of glial GABA and tonic inhibition mediated by astrocytic GABA release in the mouse model for ADHD remains unexplored. Therefore, we investigated the changes in the amount of GABA and degree of tonic inhibition in GIT1 KO mice. We observed a decreased glial GABA intensity in GIT1 KO mice compared to wild type (WT) mice and an attenuation of tonic current from cerebellar granule cells in GIT1 KO mice. Our study identifies the previously unknown mechanism of reduced astrocytic GABA and tonic inhibition in GIT1 lacking mice as a potential cause of hyperactivity disorder.