281 research outputs found
Degenerating synaptic boutons in prion disease. Microglia activation without synaptic stripping
No full textA growing body of evidence suggests that the loss of synapses is an early and major component of a number of neurodegenerative diseases. Murine prion disease offers a tractable preparation in which to study synaptic loss in a chronic neurodegenerative disease and to explore the underlying mechanisms. We have previously shown that synaptic loss in the hippocampus underpins the first behavioral changes and that there is a selective loss of presynaptic elements. The microglia have an activated morphology at this stage but they have an anti-inflammatory phenotype. We reasoned that the microglia might be involved in synaptic stripping, removing synapses undergoing a degenerative process, and that this gives rise to the anti-inflammatory phenotype. Analysis of synaptic density revealed a progressive loss from 12 weeks post disease initiation. The loss of synapses was not associated with microglia processes; instead, we found that the postsynaptic density of the dendritic spine was progressively wrapped around the degenerating presynaptic element with loss of subcellular components. Three-dimensional reconstructions of these structures from Dual Beam electron microscopy support the conclusion that the synaptic loss in prion disease is a neuron autonomous event facilitated without direct involvement of glial cells. Previous studies described synapse engulfment by developing and injured neurons, and we suggest that this mechanism may contribute to developmental and pathological changes in synapse numbers. <br/
M and P retinal ganglion cells of diurnal and nocturnal new-world monkeys
No full textM and P retinal ganglion cell morphology revealed by bio- cytin retrograde labelling was compared in two closely related New-World monkeys, Cebus and Aotus, to investigate whether nocturnal and diurnal species of primates have similar cell classes. Monkey and cat ganglion cells from regions of matching cell class densities were also compared. Cat a, cat /3, Aotus M, and Cebus M cells were similar in many aspects, but Cebus M cells had higher branching density. Cebus and Aotus P cells formed a distinct group and represent a primate specialization com-mon to diurnal and nocturnal simians.</p
MRI reveals that early changes in cerebral blood volume precede blood-brain barrier breakdown and overt pathology in MS-like lesions in rat brain
No full textMagnetic resonance imaging (MRI) is an established clinical tool for diagnosing multiple sclerosis (MS), the archetypal central nervous system neuroinflammatory disease. In this study, we have used a model of delayed-type hypersensitivity in the rat brain, which bears many of the hallmarks of an MS lesion, to investigate the development of MRI-detectable changes before the appearance of conventional indices of lesion development. In addition, we have correlated the MRI-detectable changes with the developing histopathology. Significant increases in regional cerebral blood volume (rCBV) preceded overt changes in blood–brain barrier (BBB) permeability, T2 relaxation and the diffusion properties of tissue water. Thus, changes in rCBV might be a more sensitive indicator of lesion onset than the conventional indices used clinically in MS patients, such as contrast enhancement. In addition, we show that BBB breakdown, and consequent edema formation, are more closely correlated with astrogliosis than any other histopathologic changes, while regions of T1 and T2 hypointensity appear to reflect hypercellularity
Morphological and functional abnormalities in mitochondria associated with synaptic degeneration in prion disease
No full textSynaptic and dendritic pathology is a well-documented component of prion disease. In common with other neurodegenerative diseases that contain an element of protein misfolding, little is known about the underlying mechanisms of synaptic degeneration. In particular, in prion disease the relationship between synaptic malfunction, degeneration, and mitochondria has been neglected. We investigated a wide range of mitochondrial parameters, including changes in mitochondrial density, inner membrane ultrastructure, functional properties and nature of mitochondrial DNA from hippocampal tissue of mice with prion disease, which have ongoing synaptic pathology. Our results indicate that despite a lack of detectable changes in either mitochondrial density or expression of the mitochondrial proteins, mitochondrial function was impaired when compared with age-matched control animals. We observed changes in mitochondrial inner membrane morphology and a reduction in the cytochrome c oxidase activity relative to a sustained level of mitochondrial proteins such as porin and individual, functionally important subunits of complex II and complex IV. These data support the idea that mitochondrial dysfunction appears to occur due to inhibition or modification of respiratory complex rather than deletions of mitochondrial DNA. Indeed, these changes were seen in the stratum radiatum where synaptic pathology is readily detected, indicating that mitochondrial function is impaired and could potentially contribute to or even initiate the synaptic pathology in prion disease
«Per esse ad beatum esse». Biblical exegesis as a tool for the intellectual and moral restoration of man in the work of Hugh of St. Victor (1096-1141)
No full textWydział Filozofii, Instytut Filozofii; promotor: dr hab. Andrzej StefańczykDysertacja pt. «Per esse ad beatum esse». Egzegeza biblijna jako narzędzie intelektualnej i moralnej restauracji człowieka w twórczości Hugona ze św. Wiktora (1096-1141) zawiera filozoficzną wizję odnowy człowieka, który na skutek grzechu pierworodnego, utracił zdolność poznawania i miłowania Stwórcy. Jej autorem jest wiktoryński myśliciel, Hugon ze św. Wiktora, związany z dwunastowiecznym opactwem św. Wiktora pod Paryżem. Restauracja słabej, ludzkiej kondycji [esse], której celem jest życie szczęśliwe [beatum esse] w zamyśle Hugona ma dokonać się dwutorowo: na płaszczyźnie intelektualnej poprzez dotarcie do prawdy oraz na płaszczyźnie moralnej poprzez odzyskanie dobra, czyli życie cnotliwe. Narzędziem dla integralnej odnowy człowieka Hugon uczynił egzegezę biblijną. Dowiódł, że właściwie uprawiana egzegeza powinna korzystać z zasobu nauk filozoficznych, pośród których uprzywilejowane miejsce zajmują sztuki wyzwolone [artes liberales]. W ten sposób połączył poszczególne stopnie egzegezy biblijnej ze stopniami integralnej odnowy człowieka. Analiza i interpretacja najważniejszych dzieł Hugona ze św. Wiktora pokazała, że człowiek nie może odzyskać prawdziwego szczęścia wyłącznie dzięki swoim naturalnym zdolnościom. Potrzebuje pomocy z zewnątrz, aby dokonała się w nim intelektualno-moralna restauracja. Stwórca, w zamyśle Hugona, pozostawił ludzkości drogi wyjścia z nieszczęśliwego położenia. Jeżeli człowiek, czerpiąc ze skarbca rozmaitych nauk konstytuujących filozofię, zechce wejść na egzegetyczną drogę odnowy, wówczas doświadczy szczęścia dzięki życiu w prawdzie i w cnocie.
Dissertation entitled «Per esse ad beatum esse». Biblical exegesis as a tool for the intellectual and moral restoration of man in the work of Hugh of St. Victor (1096-1141) contains a philosophical vision of the restoration of man, who, as a result of original sin, lost the ability to know and love the Creator. Its author is a victorine thinker, Hugh of St. Victor, associated with the 12th-century abbey of St. Victor near Paris. The restoration of the weak human condition [esse], the goal of which is to live a happy life [beatum esse] in Hugh's intention is to be accomplished in two ways: on the intellectual plane by reaching the truth, and on the moral plane by recovering the good, i.e., living a virtuous life. Hugh made biblical exegesis the tool for integral human renewal. He proved that properly practiced exegesis should draw on the stock of philosophical sciences, among which the liberal arts [artes liberales] have a privileged place. In this way, he linked the various degrees of biblical exegesis with the degrees of integral human renewal. The analysis and interpretation of the most important works of Hugh of St. Victor showed that man cannot regain true happiness through his natural abilities alone. He needs outside help for an intellectual and moral restoration to take place in him. The Creator, in Hugh's idea, left to mankind ways out of an unhappy position. If man, drawing from the treasury of the various sciences that constitute philosophy, is willing to embark on the exegetical path of restoration, then he will experience happiness through a life of truth and virtue
Anselm of Canterbury and the Development of Theological Thought, c. 1070-1141
No full textThis thesis explores the role of Anselm of Canterbury (1033-1109) in the development of theological thought in the late eleventh and early twelfth centuries. It aims to demonstrate that Anselm’s thought had a greater impact on the early development of scholastic theology than is often recognized, particularly in the areas of the doctrine of the incarnation and redemption, but also in his discussion of freedom and sin. Through his explanation of the economy of salvation in terms of making satisfaction for sin, and his rejection of modes of discussion that focussed on the rights and role of the devil, Anselm’s writing on the theology of the redemption provided a framework for the discussion of later authors such as Hugh of St Victor, Peter Abelard, Bernard of Clairvaux and authors associated with the School of Laon, among others. Such discussion often utilized Anselm as an explicator of difficult passages in patristic theology, notably Augustine, and his work was most controversial when he was thought to have contradicted earlier authority. Anselm was involved in contemporary polemics with both Jews and Christian theologians, as well as producing works that explored profound theological and metaphysical ideas. In his emphasis on the place and role of reason in divine questions, he crossed the boundaries between ‘monastic’ and ‘scholastic’ thought. Through an exploration of Anselmian elements in the thought of a variety of authors from the late eleventh and early twelfth centuries, this thesis aims to contribute to a broadening understanding of the legacy of this great thinker
Hugh of Saint Victor’s Treatise De verbo Dei
No full textThis article presents the translation of the treatise De verbo Dei, one of the several minor works of Hugh of Saint Victor (c. 1096–1141), which are known under the joint title Sex opuscula spiritualia. Hugh was a philosopher, a theologian, and a mystic, one of the main representatives of the Parisian Victorine School, an author increasingly present in Polish specialist literature. Hugh’s opuscle is an excellent exemplum of the twelfth-century monastic method of Scriptural interpretation. It is an exegesis of a short New Testament fragment, just a few verses of the Letter to the Hebrews (4:12–5:2).W niniejszym artykule przedkłada się tłumaczenie jednego spośród kilku pomniejszych, znanych pod wspólnym tytułem Sex opuscula spiritualia, dziełek Hugona ze Świętego Wiktora (ok. 1096–1141) – filozofa i teologa oraz mistyka, jednego z głównych przedstawicieli paryskiej szkoły wiktoryńskiej, autora coraz bardziej w polskim piśmiennictwie specjalistycznym obecnego – tłumaczenie mianowicie traktatu De verbo Dei. Utwór ten jest znakomitym exemplum dwunastowiecznej, monastycznej metody interpretacji Biblii. Stanowi go egzegeza króciutkiego fragmentu nowotestamentalnego, kilku zaledwie wersetów Listu do Hebrajczyków (4,12–5,2)
Investigations into the immune modulatory role of HSPB5
No full textSmall heat-shock proteins are conserved molecular entities present in all mammalian cells. They have historically been studied in the context of being intracellular molecular chaperones that are constitutively expressed, with a capacity to be induced by cellular stress, in order to promote and remediate protein folding. More recently however, growing evidence suggests that the action of small heat-shock proteins is not limited to protein folding but also extends to a wider range of important cellular roles. Of the 11 small heat-shock proteins that are expressed in mammalian cells, only 4, HSPB1, HSPB5, HSPB6 and HSPB8, are expressed in the central nervous system (CNS). The role of these small heat-shock proteins in the CNS is thought to be protective as they show widespread upregulation during several neurological conditions. Confoundingly however, studies from R6/2 animal models of Huntington’s disease show a selective reduced expression of HSPB5 in these animals, raising pertinent questions as to whether this reduction is cause or effect of the condition. Here, we have investigated whether reduced expression of HSPB5 has a detrimental effect, focussing specifically on HSPB5’s proposed immune modulatory role. Using mice inoculated with S. typhimurium, we found that, in our hands, mice lacking HSPB5 did not appear to be phenotypically different from wild type animals and equally, the reduced expression of HSPB5 did not exacerbate systemic inflammation or potentiate disease progression. Furthermore, to investigate HSPB5’s role in the CNS, we inoculated animals with ME7 Prion and also found that deficiency in HSPB5 did not alter phenotype or behaviour and did not negatively influence disease progression. Lastly, we investigated whether the reduced expression of HSPB5 as observed in R6/2 animals was reciprocated in humans. Our findings show that in humans disease, there is no reduction of HSPB5. Our findings suggests that in C57BL/6 animals, HSPB5 does not appear to have an immune modulatory role; they also highlight how data obtained from animal models should be taken tentatively
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