A mitokondriális UCP2 mint neuromodulator és neuroprotektor, szerepe a Parkinson-kór megelőzésében és gyógyításában = Role of mitochondrial UCP2 as a neuromodulant and neuroprotectant in the prevention and treatment of Parkinson disease

Kutatási eredményeink hozzájárulnak egy újszerű mitochondriális mechanizmus felismeréséhez, amely döntő szerepet játszik a neurodegeneráció megakadályozásában. Kimutattuk, hogy a neurodegeneráció különböző modelljeiben (pl. a Parkinson-kór) a mitochondriális uncoupling protein 2-nek (UCP2) jelentős szerepe van. A UCP2 megjelenése és a különböző neuron populációk várható túlélése, valamint degenerációja között szoros korreláció volt kimutatható, ami egyértelműen alacsonyabb sejtpusztulásban nyilvánult meg indukált neurodegerenáció után. Bizonyítottuk, hogy a koenzim-Q (CoQ) -amely a UCP2 kofaktora- adagolásának hatására a neuron elhalás és a dopamin kiürülés csökkent, valamint a UCP2, koenzim-Q által történő aktiválása a dopamin sejtek megnövekedett védelmét eredményezi a degenerációval szemben. Megállapítottuk továbbá, hogy az indukuál sejthalál szignifikánsan alacsonyabb volt a ghrelinnel (gyomorból származó metabolikus hormon) kezelt állatokban. A ghrelin előkezelésben részesült állatok az exogen ghrelin alkalmazása után, kisseb morbiditást mutattak és kevesebb dopamine sejtjük pusztult el a substantia nigraban. A ghrelin hiánya csökkenti a dopamine sejtek túlélési lehetőségét az indukált neurodegenerációban. Bizonyítást nyert, hogy a ghrelin segíti a dopamine sejtek túlélését, támogatja a szinaptikus plaszticitást mind a középagyi dopamine sejtekben, mind a hippocampusban. | Our results revealed a significant mitochondrial mechanism, which play a key role in the inhibition of neuronal degeneration. We showed that in various models of neurodegeneration (e.g. Parkinson's disease) the mitochondrial uncoupling protein 2 (UCP2) plays a important role. The expression of UPC2 and the survival of various neuron populations exhibited a strong positive correlation: after induced neurodegeneration the presence of UPC2 resulted in a higher survival rate. We also showed that application of coenzyme Q (CoQ) - which is the cofactor of UPC2 - increased the survival rate of neurons along with a decrease of dopamine release. Thus, activation of UPC2 by CoQ increased the survival rate of dopaminergic cells, and protected them from degeneration. Furthermore we showed that induced cell death was significantly lower in animals treated with ghrelin, a gastric metabolic hormone. Animals pretreated with exogenic gherlin exhibited lower morbidity and the amount of degenerated dopaminergic cells in the subtancia nigra were also lower. Absence of gherlin lowers the survival rate of dopaminergic neurons in induced neurodegeneration. We proved, that gherlin facilitates synaptic plasticity of the midbrain and hippocampal dopaminergic neurons and also helps the survival and preservation of these cells

'Monster... -omics': on segmentation, re-segmentation, and vertebrae formation in amphibians and other vertebrates

Background: The axial skeleton is one of the defining evolutionary landmarks of vertebrates. How this structure develops and how it has evolved in the different vertebrate lineages is, however, a matter of debate. Vertebrae and vertebral structures are derived from the embryonic somites, although the mechanisms of development are different between lineages. Discussion: Using the anecdotal description of a teratological newt (Triturus dobrogicus) with an unusual malformation in its axial skeleton, we review, compare, and discuss the development of vertebral structures and, in particular, the development of centra from somitic cellular domains in different vertebrate groups. Vertebrae development through re-segmentation of the somitic sclerotomal cells is considered the general mechanism among vertebrates, which has been generalized from studies in amniotic model organisms. The prevalence of this mechanism among anamniotes is, however, controversial. We propose alternative developmental mechanisms for vertebrae formation that should be experimentally tested. Summary: Research in model organisms, especially amniotes, is laying the foundations for a thorough understanding of the mechanisms of development of the axial skeleton in vertebrates, foundations that should expand the extent of future comparative studies. Although immersed in the ‘-omics’ era, we emphasize the need for an integrative and organismal approach in evolutionary developmental biology for a better understanding of the causal role of development in the evolution of morphological diversity in nature.JV was supported by the NKFP project (Faunagenezis 3B-02304) from the National Office for Research and Technology, Hungary, and the Hungarian Scientific Research Fund (OTKA K84071). DB was partially supported by the National Science Foundation EF-0334939 project (USA) and a JAE-DOC fellowship from the CSIC (Spain) under the program “Junta para la Ampliación de Estudios” co-financed by the European Social Fund (ESF). The authors also thank the Unit of Information Resources for Research (URICI-CSIC) for the co-financing of this publication in Open Access.We also acknowledge institutional support from the Unit of Information Resources for Research at the “Consejo Superior de Investigaciones Científicas” (CSIC) for the article-processing charges contribution.S

Endocardiális myocardiális pacemaker elektródák hatása a szívizomzatra = The influence of myocardial pacemaker electrodes to the heart musculature

Huszonkét 3-4 hónapos, sertésbe összesen 28 pacemaker elektródát ültettünk be. A kísérleti állatokat 3 hónapon keresztül tartottuk. A kísérlet során az állatok több mint felében tapasztaltunk súlyos fokú komplikáció kialakulását, így végül 10 állatba beültetett 13 elektróda elektromos adatait tudtuk feldolgozni. Nem találtunk szignifikáns különbséget sem a kétféle fixációjú ingerelt elektróda jelnagysága, sem küszöb ingerlési potenciálja között. Nem volt szignifikáns különbség az aktív fixációjú endocardiális ingerelt és ingerlés nélküli elektródák ellenállásában, küszöb ingerlési potenciáljában, ill. jelnagyságában sem. Szöveti reakciókat 20 sertésből származó szívizom mintákon vizsgáltuk. A vizsgált elváltozások előfordulásában sem a pacemaker elektróda típusa, sem az ingerlő feszültség nem volt meghatározó. A nem ingerelt elektródák végénél és környezetükben sokszor az ingereltekével azonos reakciók jelentek meg. Így azt a következtetést vontuk le, hogy a pacemaker elektródák körül kialakuló reakcióban az elektródavégek elektromos tulajdonságainak nincs meghatározó szerepe. Mostani vizsgálatainkban nem tudtunk a bekövetkező szövettani reakció mértéke és az elektróda elektromos paramétereinek megváltozása között sem összefüggést találni. Kutatásunk során vizsgáltuk a setések más cardiovascularis paramétereit, továbbá a cardialis memória előfordulását is. Leírtuk a pacemaker beültetések komplikációit és ezek megelőzésének lehetőségeit is. | Pacemaker implantations were performed in twenty-two 3-4 months old swine. The animals were kept for 3 months. Severe complications were met in more than half of the experimental animals, thus 13 electrodes from 10 animals were ready for electronic testing at the end of the study. We didn't find significant difference between the threshold potential and the mean signal amplitude of the active (screw in) and passive fixated endomyocardial electrodes. Similarly, no significant differences were found between the threshold potential, mean signal amplitude and impedance of the paced and non-paced screw in electrodes. Histological samples were obtained from twenty pacemaker implanted swine. There was no association between the observed histological lesions and the electrode types or the pacing voltages. Similar histological lesions were found around the tip of paced and non-paced screw-in endomyocardial electrodes. Therefore we suggest that the histological lesions are determined almost exclusively by the electrode material and not by the fixation type or pacing parameters. We couldn't find association between the different histological lesions and the measured electrode parameters during this study. We also investigated and described other cardiovascular parameters of the pig and the occurrence of cardiac memory during pacing. We analyzed the possible causes and prevention of pacemaker implantation complication in this species

A Detailed Canine Brain Label Map for Neuroimaging Analysis

Background and aims: Dogs have recently become an important model species for comparative social and cognitive neuroscience. Brain template-related label maps are essential for functional magnetic resonance imaging (fMRI) data analysis, to localize neural responses. In this study, we present a detailed, individual-based, T1-weighted MRI-based brain label map used in dog neuroimaging analysis. Methods: A typical, medium-headed dog (a 7.5-year-old male Golden Retriever) was selected from a cohort of 22 dogs, based on brain morphology (shape, size, and gyral pattern), to serve as the template for a label map. Results: Eighty-six 3-dimensional labels were created to highlight the main cortical (cerebral gyri on the lateral and medial side) and subcortical (thalamus, caudate nucleus, amygdala, and hippocampus) structures of the prosencephalon and diencephalon, and further main parts of brainstem (mesencephalon and rhombencephalon). Discussion: Importantly, this label map is (a) considerably more detailed than any available dog brain template; (b) it is easy to use with freeware and commercial neuroimaging software for MRI and fMRI analysis; and (c) it can be registered to other existing templates, including a recent average-based dog brain template. Using the coordinate system and label map proposed here can enhance precision and standard localization during future canine neuroimaging studies

Digital Endocasting in Comparative Canine Brain Morphology

Computed tomography (CT) is one of the most useful techniques for digitizing bone structures and making endocranial models from the neurocranium. The resulting digital endocasts reflect the morphology of the brain and the associated structures. Our first aim was to document the methodology behind creating detailed digital endocasts of canine skulls. We created digital endocasts of the skulls of 24 different dog breeds and 4 wild canids for visualization and teaching purposes. We used CT scanning with 0.323×0.322×0.6 mm resolution. The imaging data were segmented with 3D Slicer software and refined with Autodesk Meshmixer. Images were visualized in 3D Slicer and surface models were converted to 3D PDFs to provide easier interactive access, and 3D prints were also generated for visualization purposes. Our second aim was to analyze how skull length and width relate to the surface areas of the prepiriform rhinencephalic, prefrontal, and non-prefrontal cerebral convexity areas of the endocasts. The rhinencephalic area ratio decreased with a larger skull index. Our results open the possibility to analyze the relationship between the skull and brain morphology, and to link certain features to behavior, and cognition in dogs

A közép- és a belső fül vizsgálata 3D képalkotó eljárások alkalmazásával kutyákban

A képalkotó eszközök használata a közép- és belső fül vizsgálatában gyakran megkerülhetetlen. A hagyományos röntgenfelvételezési technikák mellett egyre nagyobb jelentősége van a computer tomográfia (CT) és a mágneses rezonan-ciás képalkotás (MR) elterjedésének, amelyekkel vetülés nélküli, nagy felbontású és szenzitivitású képanyag nyerhető. Ezek segítségével pontosabb diagnózis, prognózis és terápiás terv állítható fel a betegség leküzdésére. A szerzők a CT-és MR-vizsgálati modalitások alkalmazását egy-egy beteg bemutatásával ismer-tetik

Automatic method for determining the number of lumbar and thoracic vertebrae in rabbits using Computer Tomography images

There are several studies dealing with the phenotypic variance of the vertebral number in the spinal column of rabbits. According to the literature the number of thoracic and lumbar vertebrae varies between 11-13 and 6-8, respectively. The length of the m. longissimus dorsi (MLD) - a valuable meat part of rabbits - is determined by the length of the vertebral column therefore the number of vertebrae may have economic importance in breeding. The aim of this study was to create an automatic counter using computed tomography (CT) images. In the first step, a skeleton binary mask was created using the radiodensity range between 120 and 3071 HU, then the lumbar and thoracic regions were processed by two different methods. The lumbar part was evaluated based on the frequency of the bone voxels along the axial plane. The number of thoracic vertebrae was determined from the number of ribs. The left and right ribs were processed separately. The developed method was tested on CT examination of 40 Hycole rabbits compared to manual evaluation. The results of the automatic algorithm had few errors: in one case in the lumbar region (2.5%) and in 3 cases in the thoracic region (5%). The automated evaluation process takes a few seconds per individual and then the program visualizes the results on a graph. The incorrectly evaluated rabbits are recognizable on graphs and they can be easily corrected with a minimal time investmen