Underlying Mechanisms of Epilepsy

This book is a very provocative and interesting addition to the literature on Epilepsy. It offers a lot of appealing and stimulating work to offer food of thought to the readers from different disciplines. Around 5% of the total world population have seizures but only 0.9% is diagnosed with epilepsy, so it is very important to understand the differences between seizures and epilepsy, and also to identify the factors responsible for its etiology so as to have more effective therapeutic regime. In this book we have twenty chapters ranging from causes and underlying mechanisms to the treatment and side effects of epilepsy. This book contains a variety of chapters which will stimulate the readers to think about the complex interplay of epigenetics and epilepsy

Protektion perineuronaler Netze der extrazellulären Matrix gegenüber Verbreitung und Einlagerung des Tau-Proteins

Tauopathien wie u.a. die Alzheimer-Demenz sind eine Gruppe neurodegenerativer Erkrankungen mit intrazellulärer Ablagerung des hyperphosphorylierten Tau-Proteins. Perineuronale Netze sind eine spezialisierte Form der extrazellulären Matrix im Zentralen Nervensystem. Sie bestehen u.a. aus Chondroitinsulfat-Proteoglykanen und Tenascin-R. Ziel der vorliegenden Arbeit war der Nachweis einer Protektion perineuronaler Netze vor Tau-Protein-Einlagerung. Zu Beginn wurde die Verteilung des Tau-Proteins und die verschiedenen Arten perineuonaler Netze in der Mauslinie C57Bl6 (Wildtyp) und deren Tenascin-R-Knockout beschrieben. Die Darstellung der Komponenten erfolgte mithilfe von Gefrierschnitten und Immunhistochemie. Um die Ausbreitung von Tau-Protein zu untersuchen, wurden organotypische Hirnschnittkulturen angelegt und markiertes Tau-Protein zugesetzt. Es wurden verschiedene Antikörper genutzt, welche bestimmte Seitenketten von Chondroitinsulfat-Proteoglykanen darstellen. Die Chondroitinsulfat-Seitenketten wurden mit dem Enzym Chondroitinase ABC entfernt, um deren Funktion zu untersuchen. Die Ergebnisse der Arbeit zeigten deutliche Unterschiede in der Verteilung von Tau-Protein. Es reicherte sich bei den Wildtypen und den Tenascin-R-Knockout-Mäusen diffus extrazellulär um Neuronen mit perineuronalen Netzen an. Im Unterschied dazu verteilte sich Tau-Protein nach der Abspaltung der Chondroitinsulfat-Seitenketten vom perineuronalen Netz gleichmäßig über die Schnittkultur ohne sich an perineuronalen Netzen anzureichern. Die vorliegende Arbeit stellt die neuroprotektive Funktion der perineuronalen Netze und insbesondere ihrer Chondroitinsulfat-Seitenketten gegenüber zugegebenem Tau-Protein heraus. Weiterhin weist sie den Verlust der neuroprotektiven Funktion gegenüber zugegebenem Tau-Protein nach Behandlung mit Chondroitinase ABC nach

The role of galectin-3 in the modulation of behavior

SAŽETAK: Uvod: Galektin-3 (Gal-3) ima značajnu ulogu u brojnim biološkim i patološkim procesima, a posebno je bitan u sazrevanju i funkcionisanju nervnog sistema i nastanku neuroinflamacije. Glavni cilj ovog istraživanja bio je ispitivanje uticaja delecije gena za Gal-3 na ponašanje kod miševa soja C57/BL6. Materijal i metode: Razlike u ponašanju su evaluirane bihevioralnim testovima koji su sprovedeni kod WT (wild-type) i Gal-3-/- (engl. knockout, KO) C57BL/6 miševa, mužjaka, starosti 20 nedelja, u bazalnim uslovima, kao i 24 sata nakon intraperitonealne aplikacije lipopolisaharida (engl. lipopolysaccharide, LPS) (u jednoj dozi, 5 mg/kg). Odmah nakon toga, životinje su žrtvovane i određivani su nivoi ekspresije gena za moždani neurotrofni faktor (engl. brain-derived neurotrophic factor, BDNF), GABA-A receptorske subjedinice i proinflamacijske citokine, IL-6 (engl. interleukin-6) i TNF-α (engl. tumor necrosis factor-α) u mozgu (hipokampusu). Rezultati: Delecija gena za Gal-3 je u bazalnim uslovima imala izražen anksiogeni efekat. Ovaj efekat je bio udružen sa smanjenjem ekspresije gena i sadržaja IL-6 i TNF-α u hipokampusu. Deficijencija Gal-3 je bila praćena i smanjenjem genske ekspresije i BDNF-imunoreaktivnosti, posebno u CA1 hipokampalnom regionu. Takođe, delecija gena za Gal-3 je izazvala smanjenje ekspresije gena za subjedinice 2 i 5 GABA-A receptora u hipokampusu. Delecija gena za Gal-3 nije pokazala prodepresantni efekat u bazalnim uslovima. Anksiogeni efekat neuroinflamacije indukovane LPS-om je kod WT miševa bio udružen sa povećanom ekspresijom gena za IL-6, TNF-α i TLR4 u hipokampusu, kao i redukcijom genske i imunohistohemijske ekspresije hipokampalnog BDNF-a, uz značajnu redukciju GABAAR2S u odnosu na vrednosti koje su detektovane u bazalnim uslovima. Međutim, deficijencija Gal-3 je sprečila povećanje IL-6 i smanjenje genske ekspresije i imunoreaktivnosti BDNF-a, kao i redukciju hipokampalnih GABA-AR2S i na taj način ublažila anksiogeni efekat akutne neuroinflamacije. Zaključak: Rezultati ovog istraživanja ukazuju na to da su naizgled suprotni efekti delecije gena za Gal-3 na nivo anksioznosti (anksiogeni efekat u bazalnim uslovima i anksiolitički efekat tokom akutne neuroinflamacije) povezani sa promenama ekspresije i sadržaja IL-6, TNF-a, TLR4, GABA-ARS i BDNF-a u hipokampusu.ABSTRACT: Intraduction: Galectin-3 (Gal-3) plays a significant role in various biological and pathological processes, and is particulary important in maturation and function of nervous system and in promotion of neuroinflammation. The principle aim of this study was to examine the effects of Gal-3 gene deletion on behavior in C57/BL6 mice strain. Material and Methods: Behavioral differences were evaluated by behavioral tests carried out on WT (wild-type) and Gal-3-/- (knockout, KO) C57BL/6 mice, males, aged 20 weeks, in basal conditions, and 24 hours after an intraperitoneal application of lipopolysaccharide (LPS) (in a single dose, 5 mg/kg). After that, animals were sacrificed and levels of gene expressions of brain-derived neurotrophic factor (BDNF), GABA-A receptor subunits and proinflammatory cytokines, IL-6 (interleukin-6) and TNF-α (tumor necrosis factor-α) in the brain (hippocampus) were evaluated. Results: Deletion of the Gal-3 gene had an anxiogenic effect in basal conditions. This effect was accompanied by decrease in the gene expression and content of IL-6 and TNF-α in hippocampus. Gal-3 deficiency was also accompanied by decreases in gene expression and BDNF-immunoreactivity, predominantly in the CA1 region of hippocampus. Besides, the deletion of the Gal-3 gene resulted in decrease of hippocampal gene expression of GABA-A receptor subunits 2 and 5. Deletion of the Gal-3 gene did not show a pro-depressant effect under basal conditions. In WT mice, the anxiogenic effect of neuroinflammation induced by LPS, was followed by increased hippocampal IL-6, TNF-α and TLR4 gene expression, as well as by decreased gene and immunohistochemical expression of BDNF in hippocampus, with a significant reduction in GABA-AR2S in comparison with the values obtained in basal condition. However, Gal-3 gene deletion prevented the increase in IL-6 and the reduction in BDNF gene expression and immunoreactivity, as well as the reduction of hippocampal GABA-AR2S, and therefore attenuated the anxiogenic effect of acute neuroinflammation. Conclusion: The results of this study show that the apparently opposite effects of Gal-3 deficiency on the level of anxiety (anxiogenic effect in basal conditions and anxiolytic effect during acute neuroinflammation) are associated with changes in the gene expression and content of IL-6, TNF-a, TLR4, GABA-ARS and BDNF in hippocampus

Novel application of the gray-level co-occurrence matrix analysis in the parvalbumin stained hippocampal gyrus dentatus in distinct rat models of Parkinson's disease.

To reveal the best choice of algorithm for parvalbumin-immunostained images of the hippocampal gyrus dentatus in two distinct rat models of Parkinson's disease (PD), particularly in terms of extracting the crucial information from the image, we tested whether the impact of experimentally induced dopaminergic (hemiparkinsonism) vs. cholinergic (PD cholinopathy) innervation impairment on the parvalbumin stained GABA interneurons could be detected using two separate algorithms, the fractal box-count and the gray-level co-occurrence matrix analysis (GLCM) algorithms. For the texture and fractal analysis of the hippocampal gyrus dentatus images, we used.tif images from three experimental groups of adult male Wistar rats: control rats, rats with Parkinson disease (PD) cholinergic neuropathology (with a PPT lesion), and hemiparkinsonian rats (with a SNpc lesion). For the suprapyramidal layer of the gyrus dentatus ASM and Entropy differentiated the images of the SNpc lesion versus the images of the control and the PPT lesion subjects, with significantly higher ASM and lower Entropy, indicating the homogenization of the images and their lower gray-level complexity. The infrapyramidal images of the SNpc group were differentiated versus the images from the control and PPT groups in terms of all the GLCM parameters: they showed lower mean Entropy and Contrast and higher ASM, Correlation and IDM. These results strongly suggest a rise in the uniformity, homogeneity and orderliness in the gray-levels of images from the SNpc group. Our results indicate that GLCM analysis is a more sensitive tool than fractal analysis for the detection of increased dendritic arborization in histological images