1,721,014 research outputs found
Axotomy dependent purinergic and nitrergic co-expression.
No full textDifferent lines of evidence indicate that ATP and nitric oxide (NO) play key roles in mediating neuronal responses after cell damage. Purinergic and nitrergic interactions have been proposed in non neural tissues physiological functions and, in different experimental models of brain injury, both purinergic and nitrergic activations have been reported. The present study was planned to ascertain possible relations of these two systems after brain damage. Variations in the expression of the nitric oxide synthase neuronal isoform (nNOS) enzyme, and of two subunits of purinergic ionotrophic receptors (P2X) namely P2X(1) and P2X(2) in precerebellar stations after cerebellar lesion in rats were analyzed and compared. After the lesion nNOS positive cells presented a clear increment followed by a decrement. Conversely, nNOS negative cells presented a rapid decrement in the first postlesional weeks that continued less pronounced afterward. Postlesional nNOS activation was related with time course of P2X(1) and P2X(2) activations. The capacity of the same cells to express both nNOS and P2X markers was investigated immunocytochemically. Confocal microscopy of double immunofluorescence showed a high percentage of co-localization among P2X(1)/nNOS, P2X(2)/nNOS and P2X(1)/P2X(2) in olivary and pontine neurons. In addition, NeuN/P2X(1) and NeuN/P2X(2) double immunofluorescence showed P2X(1) expressed only in neurons while P2X(2) expressed by both neurons and glia. Present data demonstrate that after cerebellar lesion nitrergic and purinergic systems are activated with similar time courses in precerebellar stations. Further, time differences in the relation between nNOS expression and cell survival suggest a multifarious role of NO in mediating cell reaction to axotomy. The tight cellular co-localization and temporal co-activation of purinergic and nitrergic markers indicate possible interactions between these two systems also in the CNS
Partial resistance of ataxin-2-containing olivary and pontine neurons to axotomy-induced degeneration.
No full textSpinocerebellar ataxia type 2 (SCA2) is caused by the expansion of a polyglutamine tract in ataxin-2, the SCA2 gene product. In spite of the identification of the genetic defect and the coded protein, the function of wild-type ataxin-2 has not been clarified. In order to identify the possible resistance of ataxin-2-containing neurons to degeneration, we investigated in this study the distribution and the characteristics of cell reaction to axotomy in ataxin-2-positive olivary and pontine neurons in a model of cerebellar damage represented by hemicerebellectomy. We also performed double immunofluorescence studies of ataxin-2 and purinergic receptors to characterize ataxin-2-positive surviving neurons. The present data demonstrated that after axotomy olivary and pontine ataxin-2-expressing neurons survived longer than the ataxin-2-negative cell population. Cell counting performed in the different olivary subdivisions failed to reveal any topographical prevalence in the distribution of ataxin-2-positive neurons. Therefore, the relative resistance to axotomy appears to be an intrinsic property of the ataxin-2 cell population. In addition, the capacity to modify the pattern of purinergic receptor expression in response to damage was present in only one subset of ataxin-2-positive surviving neurons. These data suggest that ataxin-2 is involved in resistance to degeneration phenomena which may be lost after mutation
Localization of ataxin-2 within the cerebellar cortex of the rat.
No full textSpinocerebellar ataxia type 2 is caused by a polyglutamine stretch in the protein ataxin-2 that is due to an expansion of a CAG repeat in the spinocerebellar ataxia-2 gene. The function of wild-type ataxin-2 has not been clarified. A widespread distribution of this protein throughout the brain has been reported. We examined the expression of ataxin-2 in cortical cerebellar cells of the adult rat. We performed a single label immunohistochemical study of ataxin-2 and a single label immunofluorescence study of ataxin-2 and zebrin on adjacent sections, to compare the distribution of the observed parasagittal band pattern. We also performed a double label immunofluorescence study of ataxin-2 and one of each parvalbumin, calbindin, and calretinin. Single label studies revealed that between 50% and 70% of the Purkinje cells express ataxin-2. The abundance of ataxin-2 was different between hemisphere and vermis, with a clear prevalence for the former. Furthermore, the distribution of ataxin-2-positive Purkinje cells showed a peculiar alternating parasagittal band pattern. Among the other cortical cerebellar cells only basket and granule cells showed ataxin-2 staining. Our dual label studies showed that about 50% of calbindin and more than 70% of parvalbumin-immunoreactive Purkinje cells were also labeled for ataxin-2. The uneven distribution of ataxin-2 expression in the Purkinje cell layer does not support the hypothesized link between ataxin-2 content and cell vulnerability. The differences in ataxin-2 expression among the cell types of cerebellar cortex, on the other hand, suggest a possible correlation between ataxin-2 content and cell function
Methylprednisolone treatment delays remote cell death after focal brain lesion.
No full textGlucocorticoids have a prominent role in the treatment of CNS injuries. However, the cellular consequences of glucocorticoid treatment on remote degenerative responses after focal brain lesions have been poorly investigated. Here we examine the effectiveness of a high dose (50 mg/kg) of methylprednisolone sodium succinate (MPSS) in reducing neuronal loss, glial response and glial-derived inflammatory mediators in inferior olive and pontine nuclei after lesion of the contralateral cerebellar hemisphere using immunohistochemistry and Western blot techniques. Quantitative analysis demonstrated that MPSS treatment significantly improved the survival of neurons in remote precerebellar stations. This survival was accompanied by reduction in the postlesional activation of microglia, astrocytes and interleukin-1 beta (IL-1beta). Cell death resumed after suspension of MPSS treatment and this delayed wave of cell loss was paralleled by reactivation of the inflammatory markers analyzed. The present study confirms the importance of inflammatory events in inducing remote cell death and that this type of degeneration can be delayed by MPSS treatment. Furthermore, the sustained effect of MPSS treatment, up to 28 days postlesion, and the reactivation of the degenerative phenomena after its suspension, support the hypothesis that glucocorticoid treatment, although capable of delaying cell death mechanisms, is not effective in blocking the cascade of remote degenerative events started by the primary lesion
Huntingtin distribution among striatal output neurons of normal rat brain.
No full textHuntingtin is the protein whose mutation leads to Huntington's disease (HD). The protein is heterogeneously distributed in the telencephalon, and not consistently correlated with cell vulnerability in HD [Fusco, F.R., Chen, Q., Lamoreaux, W.J., Figueredo-Cardenas, G., Jiao, Y., Coffman, J.A., Surmeier, D.J., Honig, M.G., Carlock, L.R., and Reiner, A., J. Neurosci., 19 (1999) 1189-1202]. The aim of our study was to investigate a possible preferential distribution of huntingtin among the two main striatal output pathways, namely, the striatonigral and the striatopallidal circuit. Dual label immunofluorescence by means of confocal microscopy was used to detect the presence of huntingtin among striatal projection neurons identified by their cellular content of Substance P, Enkephalin, CB1 receptor, and D1a dopamine receptor. Our data showed that striatopallidal neurons co-containing SP and D1a [Surmeier, D.J., Song, W.J., and Yan, Z., J. Neurosci., 16 (1996) 6579-6591] co-localized with huntingtin in a higher proportion than striatonigral neurons
N-arachidonoyl-dopamine tunes synaptic transmission onto dopaminergic neurons by activating both cannabinoid and vanilloid receptors.
No full textIn the present study, we used electrophysiological, biochemical, and confocal microscopy techniques, to investigate the functional role of transient receptor potential vanilloid type 1 (TRPV1) and cannabinoid type 1 receptors (CB1-R) in the substantia nigra pars compacta (SNpc) and their stimulation by the endocannabinoid N-arachidonoyl-dopamine (NADA). Liquid chromatography-mass spectrometry analyses revealed that a NADA-like compound is produced in substantia nigra slices, in conditions of hyperactivity. Moreover, the functional role of both TRPV1 and CB1-R in modulating synaptic transmission in this area was suggested by confocal microscopy data, showing TRPV1 and CB1-R immunoreactivity in punctate structures, probably representing synaptic contacts on cell bodies of the SNpc. In patch-clamp recordings from dopamine (DA) neurons of the SNpc, we found that NADA increases or reduces glutamatergic transmission onto DA neurons by activating TRPV1 and CB1 receptors, respectively, whereas it decreases GABAergic transmission via CB1 stimulation. Facilitation of glutamate release through TRPV1 was blocked in the presence of a selective blocker of the putative endocannabinoid membrane transporter (EMT), indicating that NADA needs to be taken up by cells to interact with this receptor. In line with these data, biochemical results demonstrated that NADA selectively acted at CB1-R when its re-uptake was blocked. Altogether these data demonstrate a significant role exerted by the endocannabinoid/endovanilloid NADA in the regulation of synaptic transmission to DA neurons of the SNpc. Moreover, they highlight a key function of the EMT transporter in promoting the stimulation of TRPV1 or CB1-R, thus favoring facilitation or inhibition of glutamate synaptic release
Repetitive transcranial magnetic stimulation reduces remote apoptotic cell death and inflammation after focal brain injury
Full text linkAbstract: Background: After focal brain injuries occur, in addition to the effects that are attributable to the primary site of damage, the resulting functional impairments depend highly on changes that occur in regions that are remote but functionally connected to the site of injury. Such effects are associated with apoptotic and inflammatory cascades and are considered to be important predictors of outcome. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique that is used to treat various central nervous system (CNS) pathologies and enhance functional recovery after brain damage.
Objective: This study examined the efficacy of rTMS in mitigating remote degeneration and inflammation and in improving functional recovery in a model of focal brain damage.
Methods: Rats that were undergoing hemicerebellectomy (HCb) were treated with an rTMS protocol for 7 days, and neuronal death indices, glial activation, and functional recovery were assessed.
Results: rTMS significantly reduced neuronal death and glial activation in remote regions and improved functional recovery.
Conclusions: Our finding opens up a completely new scenario for exploiting the potential of rTMS as an anti-apoptotic and anti-inflammatory treatment
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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