Effect of periapical inflammation on calcium binding proteins and ERK in the trigeminal nucleus / Efecto de la inflamación periapical sobre las proteínas fijadoras de calcio y ERK en el núcleo trigeminal

Peripheral inflammation induces plastic changes in neurons and glia which are regulated by free calcium and calcium binding proteins (CaBP). One of the mechanisms associated with the regulation of intracellular calcium is linked to ERK (Extracellular Signal-Regulated Kinase) and its phosphorylated condition (pERK). ERK phosphorylation is important for intracellular signal transduction and participates in regulating neuroplasticity and inflammatory responses. The aim of this study is to analyse the expression of two CaBPs and pERK in astrocytes and neurons in rat trigeminal subnucleus caudalis (Vc) after experimental periapical inflammation on the left mandibular first molar. At seven days post-treatment, the periapical inflammatory stimulus induces an increase in pERK expression both in S100b positive astrocytes and Calbindin D28k positive neurons, in the ipsilateral Vc with respect to the contralateral side and control group. pERK was observed coexpressing with S100b in astrocytes and in fusiform Calbindin D28k neurons in lamina I. These results could indicate that neural plasticity and pain sensitization could be maintained by ERK activation in projection neurons at 7 days after the periapical inflammation.

La inflamación periférica induce cambios plásticos en las neuronas y en la glía, los cuales están regulados por el calcio libre y las proteínas fijadoras calcio (CaBP). Uno de los mecanismos asociados con la regulación del calcio intrace-lular está vinculado con la fosforilación de la pro teína quinasa ERK. Asimismo, ERK fosforilado es importante para la trans-ducción de señales intracelulares y participa en la regulación de la neuroplasticidad y las respuestas inflamatorias. El objetivo de este estudio es analizar la expresión de dos CaBPs y pERK en astrocitos y neuronas del subnúcleo caudal del trigémino (Vc) después de una inflamación periapical experimental en el primer molar inferior izquierdo en ratas. A los siete días posteriores al tratamiento, el estímulo inflamatorio periapical induce un aumento en la expresión de pERK, en el número de astrocitos positivos para la proteína marcadora astroglial S100b y en neuronas positivas para Calbindina D28k, en el Vc ipsilateral respecto del lado contralateral y el grupo de control. Además, se observó coexpresión de pERK tanto en astrocitos S100b positivos, como en neuronas fusiformes Calbindin D28k positivas, de la lámina I. Estas observaciones podrían indicar que la neuroplasticidad y la sensibilización al dolor podrían mantenerse mediante la activación de ERK en las neuronas de proyección a los 7 días de la inflamación periapical.

The protection effect and mechanism of hyperbaric oxygen therapy in rat brain with traumatic injury

Abstract Purpose: To investigate the effect of hyperbaric oxygen therapy (HBOT) on traumatic brain injury (TBI) outcome. Methods: The modified Marmarou's weight drop device was used to generate non-lethal moderate TBI rat model, and further developed in vitro astrocytes culturing system. Then, we analyzed the expression changes of interested genes and protein by quantitative PCR and western blot. Results: Multiple HBO treatments significantly reduced the expression of apoptosis promoting genes, such as c-fos, c-jun, Bax and weakened the activation of Caspase-3 in model rats. On the contrary, HBOT alleviated the decrease of anti-apoptosis gene Bcl-2 and promoted the expression of neurotrophic factors (NTFs), such as NGF, BDNF, GDNF and NT-3 in vivo. As a consequent, the neuropathogenesis was remarkably relied with HBOT. Astrocytes from TBI brain or those cultured with 21% O2 density expressed higher NTFs than that of corresponding controls, from sham brain and cultured with 7% O2, respectively. The NTFs expression was the highest in astrocytes form TBI brain and cultured with 21% O2, suggesting a synergistic effect existed between TBI and the following HBO treatment in astrocytes. Conclusion: Our findings provided evidence for the clinical usage of HBO treating brain damages.

Andrographolide protects mouse astrocytes against hypoxia injury by promoting autophagy and S100B expression

Andrographolide (ANDRO) has been studied for its immunomodulation, anti-inflammatory, and neuroprotection effects. Because brain hypoxia is the most common factor of secondary brain injury after traumatic brain injury, we studied the role and possible mechanism of ANDRO in this process using hypoxia-injured astrocytes. Mouse cortical astrocytes C8-D1A (astrocyte type I clone from C57/BL6 strains) were subjected to 3 and 21% of O2 for various times (0-12 h) to establish an astrocyte hypoxia injury model in vitro. After hypoxia and ANDRO administration, the changes in cell viability and apoptosis were assessed using CCK-8 and flow cytometry. Expression changes in apoptosis-related proteins, autophagy-related proteins, main factors of JNK pathway, ATG5, and S100B were determined by western blot. Hypoxia remarkably damaged C8-D1A cells evidenced by reduction of cell viability and induction of apoptosis. Hypoxia also induced autophagy and overproduction of S100B. ANDRO reduced cell apoptosis and promoted cell autophagy and S100B expression. After ANDRO administration, autophagy-related proteins, S-100B, JNK pathway proteins, and ATG5 were all upregulated, while autophagy-related proteins and s100b were downregulated when the jnk pathway was inhibited or ATG5 was knocked down. ANDRO conferred a survival advantage to hypoxia-injured astrocytes by reducing cell apoptosis and promoting autophagy and s100b expression. Furthermore, the promotion of autophagy and s100b expression by ANDRO was via activation of jnk pathway and regulation of ATG5.

Are astrocytes executive cells within the central nervous system? / ¿Son los astrocitos células ejecutivas dentro del Sistema Nervioso Central?

ABSTRACT Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS) by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations signal that some of the primary degenerative diseases of the CNS, like frontotemporal dementia, Parkinson’s disease, Alzheimer’s dementia, Huntington’s dementia, primary cerebellar ataxias and amyotrophic lateral sclerosis, all of which affect the human species exclusively, may be due to astroglial dysfunction. This hypothesis is supported by observations that demonstrated that the killing of neurons by non-neural cells plays a major role in the pathogenesis of those diseases, at both their onset and their progression. Furthermore, recent findings suggest that astrocytes might be involved in the pathogenesis of some psychiatric disorders as well.

RESUMEN Evidencias experimentales sugieren que los astrocitos desempeñan un rol crucial en la fisiología del sistema nervioso central (SNC) modulando la actividad y plasticidad sináptica. En base a lo actualmente conocido creemos que los astrocitos participan, en pie de igualdad con las neuronas, en los procesos de información del SNC. Además, observaciones experimentales y humanas encontraron que algunas de las enfermedades degenerativas primarias del SNC: la demencia fronto-temporal; las enfermedades de Parkinson, de Alzheimer, y de Huntington, las ataxias cerebelosas primarias y la esclerosis lateral amiotrófica, que afectan solo a los humanos, pueden deberse a astroglíopatía. Esta hipótesis se sustenta en hallazgos que demostraron que la muerte neuronal que en ellas ocurre es debida al compromiso de células no-neuronales que juegan rol principal en su iniciación y desarrollo. Más aún, observaciones recientes señalan que los astrocitos podrían estar implicados en la patogenia de algunas enfermedades psiquiátricas.

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. .

Esclerosis lateral amiotrófica: ¿es el astrocito la célula primariamente dañada? / [Amyotrophic lateral sclerosis: is the astrocyte the cell primarily involved?].

So far, amyotrophic lateral sclerosis (ALS) is thought as due to a primary insult of the motor neurons. None of its pathogenic processes proved to be the cause of the illness, nor can be blamed environmental agents. Motor neurons die by apoptosis, leaving the possibility that their death might be due to an unfriendly environment, unable to sustain their health, rather than being directly targeted themselves. These reasons justify an examination of the astrocytes, because they have the most important role controlling the neurons’ environment. It is known that astrocytes are plastic, enslaving their functions to the requirements of the neurons to which they are related. Each population of astrocytes is unique, and if it were affected the consequences would reach the neurons that it normally sustains. In regard to the motor neurons, this situation would lead to a disturbed production and release of astrocytic neurotransmitters and transporters, impairing nutritional and trophic support as well. For explaining the spreading of muscle symptoms in ALS, correlated with the type of spreading observed at the cortical and spinal motor neurons pools, the present hypotheses suggests that the illness-causing process is spreading among astrocytes, through their gap junctions, depriving the motor neurons of their support. Also it is postulated that a normal astrocytic protein becomes misfolded and infectious, inducing the misfolding of its wild type, travelling from one protoplasmatic astrocyte to another and to the fibrous astrocytes encircling the pyramidal pathway which joints the upper and lower motoneurones.

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.

Astrocyte, the star avatar: redefined.

Until recently, the neuroscience community held the belief that glial cells such as astrocytes and oligodendrocytes functioned solely as "support" cells of the brain. In this role, glial cells simply provide physical support and housekeeping functions for the more important cells of the brain, the neurons. However, this view has changed radically in recent years with the discovery of previously unrecognized and surprising functions for this underappreciated cell type. In the past decade or so, emerging evidence has provided new insights into novel glial cell activities such as control of synapse formation and function, communication,cerebrovascular tone regulation, immune regulation and adult neurogenesis. Such advances in knowledge have effectively elevated the role of the astrocyte to one that is more important than previously realized. This review summarizes the past and present knowledge of glial cell functions that has evolved over the years, and has resulted in a new appreciation of astrocytes and their value in studying the neurobiology of human brain cells and their functions. In this review, we highlight recent advances in the role of glial cells in physiology, pathophysiology and, most importantly, in adult neurogenesis and "stemness", with special emphasis on astrocytes.

Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

PURPOSE: Reactive astrocytes are implicated in several mechanisms after central or peripheral nervous system lesion, including neuroprotection, neuronal sprouting, neurotransmission and neuropathic pain. Schwann cells (SC), a peripheral glia, also react after nerve lesion favoring wound/repair, fiber outgrowth and neuronal regeneration. We investigated herein whether cell therapy for repair of lesioned sciatic nerve may change the pattern of astroglial activation in the spinal cord ventral or dorsal horn of the rat. METHODS: Injections of a cultured SC suspension or a lesioned spinal cord homogenized extract were made in a reservoir promoted by a contiguous double crush of the rat sciatic nerve. Local injection of phosphate buffered saline (PBS) served as control. One week later, rats were euthanized and spinal cord astrocytes were labeled by immunohistochemistry and quantified by means of quantitative image analysis. RESULTS: In the ipsilateral ventral horn, slight astroglial activations were seen after PBS or SC injections, however, a substantial activation was achieved after cord extract injection in the sciatic nerve reservoir. Moreover, SC suspension and cord extract injections were able to promote astroglial reaction in the spinal cord dorsal horn bilaterally. Conclusion: Spinal cord astrocytes react according to repair processes of axotomized nerve, which may influence the functional outcome. The event should be considered during the neurosurgery strategies.

OBJETIVO: Astrócitos reativos participam de vários mecanismos após lesões do sistema nervoso central e periférico, os quais incluem neuroproteção, brotamento neuronal, neurotransmissão e dor neuropática. As células de Schwann (CS), um tipo de glia periférica, também reagem com a lesão do nervo, podendo interferir com o reparo e cicatrização, crescimento de fibras e regeneração neuronais. Investigamos aqui a possibilidade da terapia celular para o reparo do nervo ciático poder alterar o padrão da ativação astrocitária nos cornos anterior e posterior da medula espinal do rato. MÉTODOS: Suspensão de CS cultivadas ou extrato homogeneizado de medula espinal lesada de rato foram inoculados num reservatório feito a partir de dois esmagamentos aplicados no nervo ciático do rato distantes 0,5mm entre si. Injeção local de salina tamponada serviu como controle. Os ratos foram mortos uma semana após e os astrócitos da medula espinal marcados por método imunohistoquímico e quantificados por análise de imagem. RESULTADOS: No corno anterior da medula, ipsilateral à lesão, ativação astrocitária leve foi vista após as injeções de tampão ou CS, entretanto, ativação celular intensa foi observada nesta região com a inoculação neural do extrato homogeneizado de tecido medular lesado. Adicionalmente, as inoculações de CS e de extrato homogeneizado de tecido medular promoveram forte reação astrocitária no corno dorsal da medula espinal, bilateralmente. CONCLUSÕES: Os astrócitos da medula espinal reagem em função do processo de reparo do nervo lesado, o que pode influenciar o resultado funcional esperado, algo que deve ser considerado durante o planejamento da estratégia neurocirúrgica.

Degeneração esponjosa no sistema nervoso central de bezerros da raça Sindhi / Spongious degeneration in the central nervous system in Sindhi calves

Degeneração esponjosa (status spongiosus) agrupa várias alterações histológicas caracterizadas pela formação de vacúolos no neurópilo em diferentes regiões do sistema nervoso central (SNC). Essa vacuolização pode ser por edema intramielínico, como na doença da urina com odor de xarope de bordo (maple syrup urine disease) e algumas doenças tóxicas, ou por edema de astrócitos, como na citrulinemia. Este trabalho descreve degeneração esponjosa do SNC em dois bezerros, um macho e uma fêmea, da raça Sindhi. Ambos são filhos de um mesmo touro, de um rebanho que apresentava alto grau de consangüinidade. Uma fêmea nasceu normal e aos 2 meses apresentou sinais nervosos progressivos. Um macho apresentou sinais nervosos progressivos desde o nascimento. Os dois foram eutanasiados aos 4 meses de idade com acentuadas alterações do sistema nervoso central. Na necropsia o fígado de bezerro macho estava pálido. Histologicamente havia, em ambos os bezerros, discreta a acentuada vacuolização difusa do SNC, sendo mais acentuada nas camadas profundas do córtex cerebral, cápsula interna, substância branca da medula cerebelar, tronco encefálico e substância cinzenta da medula. No fígado dos dois animais havia degeneração gordurosa nos hepatócitos da região centrolobular. Na microscopia eletrônica observou-se que o status spongiosus era devido a edema astrocitário. Sugere-se que a doença é causada por um erro metabólico hereditário, diferente da doença da urina com odor de xarope de bordo.

Spongy degeneration (status spongiosus) includes many histological alterations characterized by vacuoles in the neuropile in different regions of the central nervous system (CNS). The vacuolization can be caused by intramyelinic edema, as in maple syrup urine disease and some toxic diseases, or by astrocytic edema, as in citrullinemia. This paper reports a spongy degeneration in two Sindhi calves, a female and a male. Both calves were offspring from the same bull, and the herd had high degree of inbreeding. The female calf was born normal, but progressive nervous signs were observed since 2 months old. The male calf had progressive nervous signs since it was born. Both calves were euthanized with severe nervous signs when 4 months old. At necropsy the liver was pale in the male calf. Histological alterations were mild to accentuated vacuolization, mainly in the deep cerebral cortex, cerebellar white matter, grey matter of the spinal cord, internal capsule, and brain stem. Fatty degeneration was observed in the liver of both animals. On electron microscopy it was found that the status spongiosus was caused by astrocytic edema. It is suggested that the disease is caused by a metabolic hereditary error.

Regulation of astroglia on synaptic plasticity in the CA1 region of rat hippocampus / 华中科技大学学报（医学）（英德文版）

The regulation of astroglia on synaptic plasticity in the CA1 region of rat hippocampus was examined. Rats were divided into three groups: the newly born (< 24 h), the juvenile (28-30 days) and the adult groups (90 - 100 days), with each group having 20 animals. The CA1 region of rat hippocampus was immunohistochemically and electron-microscopically examined, respectively, for the growth of astroglia and the ultrastructure of synapses. The high performance liquid chromatography was employed to determine the cholesterol content of rat hippocampus. In the newly-born rats, a large number of neurons were noted in the hippocampal CA1 region of the newly-born rats, and few astroglia and no synaptic structure were observed. In the juvenile group, a few astroglias and some immature synapses were found, which were less than those in adult rats (P < 0.01). The cholesterol content was 2.92 +/- 0.03 mg/g, 11.20 +/- 3.41 mg/g and 12.91 +/- 1.25 mg/g for newly born, the juvenile and the adult groups, respectively, with the differences among them being statistically significant (P < 0.01). Our study suggests that the astrocytes may play an important role in the synaptic formation and functional maturity of hippocampal neurons, which may be related to the secretion of cholesterol from astrocytes.

Cloning of TLR3 Isoform

Toll-like receptor (TLR) 3 is a member of the TLR family that confers innate immunity by recognizing viral pathogens. Herein, we report that the TLR3 isoform is expressed on human primary cells and cell lines. This isoform has 2, 520 bp cDNAs compared to the 2, 712 bp of full cDNA, is produced by deletion of an intron-like sequence within exon 4 and is co-expressed with wild type TLR3 in primary human astrocytes and glioblastoma cell lines. This finding suggests the TLR3 isoform in astrocytes may have a different immunological role for binding ligands during the immune response in brain.

Characterization of the Two Genes Differentially Expressed During Development in Human Fetal Astrocytes

Astrocytes are ubiquitous in the brain and have multiple functions. It is becoming clear that they play an important role in monitoring the neuromicroenvironment, information processing, and signaling in the central nervous system (CNS) in normal conditions and that they respond to CNS injuries. During the development of the CNS, astrocytes play a key role as a substrate for neuronal migration and axonal growth. To identify genes that could participate in astrocyte maturation, we used the differential display reverse transcription-PCR (DDRT-PCR) method. Human fetal astrocytes were cultured and total RNAs were isolated at intervals of 5 days for 50 days. Using 24 primer combinations, we identified a set of 18 candidate cDNAs deriving from the excised DDRT-PCR bands. DNA sequencing revealed 16 genes that have been described already. We found that RTP, TG, hTM-alpha, SPARC, TRIP7, and RPL7 genes were expressed increasingly, while HMGCR, RPL27a, NACA, NPM, and TARBP2 genes were expressed decreasingly, according to their culture stages. We also found two unidentified genes, A3 and C8, which were expressed differently in culture stages; the former was expressed decreasingly and the latter increasingly. These two genes were found in the same amount in genomic DNA from various human cells such as astrocytes, astrocytoma, trophoblasts and lymphocytes. The A3 gene was found only in human genomic DNA, but not in rat (ATr5), mouse (RAW264.7), or monkey (Vero) cells, whereas the C8 gene was found in human genomic DNA and monkey cells, but not in rat or mouse cells. We analysed these two genes for identification. There was > 92% nucleotide sequence identity between the A3 gene (3, 626 bp) and the Homo sapiens general transcription factor 3 (GTF3), and > 96% nucleotide sequence identity between the C8 gene (2, 401 bp) and the transmembrane receptor Unc5h2. These findings suggest that these two genes may participate in some functional roles within the cells.

Cross-talk between neurons and glia: highlights on soluble factors

The development of the nervous system is guided by a balanced action between intrinsic factors represented by the genetic program and epigenetic factors characterized by cell-cell interactions which neural cells might perform throughout nervous system morphogenesis. Highly relevant among them are neuron-glia interactions. Several soluble factors secreted by either glial or neuronal cells have been implicated in the mutual influence these cells exert on each other. In this review, we will focus our attention on recent advances in the understanding of the role of glial and neuronal trophic factors in nervous system development. We will argue that the functional architecture of the brain depends on an intimate neuron-glia partnership

Influencia del ácido oleico sobre la actividad angiotensinasa de astroglía cortical de rata / Influence of oleic acid in the angiotensinase activity in the cortical astroglia in rats

Objetivo. Las dietas elevadas en grasa están asociada con el desarrollo de enfermedades cerebrovasculares de distinto tipo. Distintos estudios epidemiológicos ha demostrado que la población de los países mediterráneos tienen menor porcentaje de enfermedades cerebro vasculares que la población del norte de Europa o de Estados Unidos de Norteamérica. En los países mediterráneos, la dieta habitual contiene una gran proporción de ácidos grasos monoinsaturados, mientras que en los países mas industrializados, el componente graso está constituido principalmente por grasas saturadas. Las aminopeptidasas (AP) son especialmente importantes por que están implicadas en el metabolismo y regulación de hormonas circulantes y péptidos biológicamente activos de numerosos tejidos. Algunas aminopeptidasas están relacionadas con el metabolismo de las angiotensinas en el sistema renina-angiotensina (RAS), y por tanto participan en la regulación de la presión sanguínea, tanto a nivel sistémico como local. El sistema nervioso es, probablemente, uno de los órganos mas sensibles a las alteraciones de la presión arterial. El presente trabajo se ha diseñado para estudiar el comportamiento de la actividad angiotensinasa en astrocitos de corteza frontal de rata, cultivados en presencia de distintas concentraciones de ácido oleico en el medio de cultivo. Material y métodos. La actividad angiotensinasa (aspartato-glutamato-aminopeptidasa) se analizó en cultivos primarios de astrocitos de rata, utilizando b -naftilamidas como sustratos. Resultados y conclusiones. Las disminuciones observadas en la actividad aminopeptidasa ponen de manifiesto la posible influencia del ácido oleico sobre algunos de los factores implicados en la regulación del flujo sanguíneo local o la homeostasis de líquidos y electrólitos locales en el sistema nervioso. Se discute que esta acción puede ser debida a la modificación de los procesos de comunicación intercelular mediados por uniones de tipo GAP o bien, a la modulación de los sistemas de comunicación intracelular mediados por el fosfatidilinositol y posterior activación de la proteinkinasa C, entre otros

Experimental microneurosurgery of the central and peripheral nervous system in the study of the neuronal and glial trophism and plasticity

Trauma and neurodegenerative diseases commit the nervous system. After an axotomy or nerve injury in the peripheral nervous system the regeneration of the nerve fibers and reinervation of the target are seen. In central nervous system these events are restrictive, however their occurrence are related to the state of glial reaction and the synthesis of neurotrophic factors. Basic fibroblast growth factor (bFGF) has been considered an important trophic factor for neurons and astrocytes of many central nervous system regions. In this study rats were submitted to one of following neurosurgery procedures: callosotomy, pyramidectomy or complete transection of hypoglossal nerve (XII). Sham operations were made in control animals. Seven days later animals were sacrificed and their braims processed for immunohistochemistry. Coronal sections were taken from the central nervous system and incubated with antisera against the glial fibrillary acidic protein (GFAP) or neurofilament (NF), markers for astrocyte and neuronal cell body and fibers, respectively, as well as with the antiserum against the bFGF. The degree of the labelling was quatified with computer assisted stereological methods. The analysis of the NF immunoreactivity revealed a disappearance of fibers in the white matter distal to the pyramidectomy and callosotomy, however no disapperance of NF immunoreactive neurons was found in the XII nucleus following axotomy. These changes was accompanied by a massive astrocytic reaction. The reactive astrocytes synthesized increased amounts of bFGF. These findings suggest that glial reaction synthesizing neurotrophic factors may influence the wound and repair after mechanical lesions of central nervous and subsequent neuronal trophism and plasticity which may be relevant to the regenerative process of the nervous tissue.

Control of the phosphorylation of the astrocyte marker glial fibrillary acidic protein (GFP) in the immature rat hippocampus by glutamate and calcium ions: possible key factor in astrocytic plasticity

The present review describes recent research on the regulation by glutamate and Ca2+ of the phosphorylation state of the intermediate filament protein of the astrocytic cytoskeleton, glial fibrillary acidic protein (GFAP), in immature hippocampal slices. The results of this research are discussed against a background of modern knowledge of the functional importance of astrocytes in the brain and of the structure and dynamic properties of intermediate filament proteins. Astrocytes are now recognized as partners with neurons in many aspects of brain function with important roles in neural plasticity. Site-specific phosphorylation of intermediate filament proteins, including GFAP, has been shown to regulate the dynamic equilibrium between the polymerized and depolymerized state of the filaments and to play a fundamental role in mitosis. Glutamate was found to increase the phosphorylation state of GFAP in hippocampal slices from rats in the post-natal age range of 12-16 days in a reaction that was dependent on external Ca2+. The lack of external Ca2+ in the absence of glutamate also increased GFAP phosphorylation to the same extent. These effects of glutamate and Ca2+ were absent in adult hippocampal slices, where the phosphorylation of GFAP was completely Ca2+ -dependent. Studies using specific agonists of glutamate receptors showed that the glutamate response was mediated by a G protein-linked group II metabotropic glutamate receptor (mGluR). Since group II mGluRs do not act by liberating Ca2+ from internal stores, it is proposed that activation of thereceptor by glutamate inhibits Ca2+ entry into the astrocytes andconsequently down-regulates a Ca2+-dependent dephosphorylationcascade regulating the phosphorylation state of GFAP. The functional significance of these results may be related to the narrow developmental window when the glutamate response is present. In the rat brain this window corresponds to the period of massive synaptogenesis during which astrocytes are known to proliferate. Possibly, glutamate liberated from developing synapses during this period may signal an increase in the phosphorylation state of GFAP and a consequent increase in the number of mitotic astrocytes.

Heterogeneity of median and lateral midbrain radial glia and astrocytes

In the developing mammalian midbrain, radial glial cells are divided into median formations and lateral radial systems with differential properties including rate and timing of cell proliferation, expression of cytoskeletal and calcium-binding proteins, storage of glycogen and relations to afferent fiber systems. To test hypothesis that radial glial cells of median and lateral midbrain sectors and/or their derivatives are heterogeneous in their relations with local neurons, an in vitro system has been developed and has also been characterized in terms of extracellular matrix (ECM) components. Confluent astrocyte cultures, derived from median (M) or lateral (L) embryonic mouse midbrain sectors, were used as substrates for culturing dissociated cells from median (m) or lateral (l) sectors of embryonic midbrains. In spite of the morphological invariance of glial substrates at confluency, cells that were plated onto these substrates and that were immunoreactive for neuronal markers (MAP2, polysialylated N-CAM or betaIII tubulin) showed differences in the aggregation of somata and in the length, caliber and branching of neurites. These differences, which depend mostly on the sector of origin of astrocytes (L: permissive, M: non-permissive for neuronal growth), suggest that the substrates may differ in adhesiveness and/or their carrying of growth-promoting vs. growth-interfering molecules. Indeed, L and M cultures differ in laminin deposition patterns (L: fibrillar, M: punctate pattern). Furthermore, sulfated glycosaminoglycans (s-GAGs) isolated from the pericellular (P), intracellular (I) and extracellular (E) compartments of these sectoral cultures also showed correlations with the ability to support neurite growth. The total amount of s-GAGs in M cultures was twice that in L cultures and was particularly high in the P compartment, with about 3 times as much heparan sulfate (HS) and about 15 times as much chondroitin sulfate (CS) in this fraction of M than in the corresponding compartment of L glia. Our results indicate that cultured astrocytes have heterogeneous properties including different organizatio of their extracellular matrix that reflect the roles played by their parent radial glia in regions favorable to axonal growth or barrier regions of the developing brain.

Macroglia cells of the macaque monkey retina

There are two types of macroglia cells in the macaque monkey retina: Müller cells and astrocytes. Both cell types are in close contact with neuronal structures as well as with the retinal vasculature and are thus well suited for their many physiological tasks. Müller cells ubiquitously traverse the whole thickness of the retina whereas astrocytes are only found in the ganglion cell and nerve fiber layers of vascularized retinal regions. In the adult, astrocytes are very scarce in the central 4mm around the fovea, a region coinciding with peak Müller cell densities. During development this area is transiently occupied by astrocytes which then disappear during the first postnatal weeks at least in part through apoptosis. Possible reasons for this transiency will be discussed.