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排序方式: 共有132条查询结果,搜索用时 15 毫秒
1.
Sanaz Gabery Nellie Georgiou-Karistianis Sofia Hult Lundh Rachel Y. Cheong Andrew Churchyard Phyllis Chua Julie C. Stout Gary F. Egan Deniz Kirik ?sa Petersén 《PloS one》2015,10(2)
Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Non-motor symptoms and signs such as psychiatric disturbances, sleep problems and metabolic dysfunction are part of the disease manifestation. These aspects may relate to changes in the hypothalamus, an area of the brain involved in the regulation of emotion, sleep and metabolism. Neuropathological and imaging studies using both voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) as well as positron emission tomography (PET) have demonstrated pathological changes in the hypothalamic region during early stages in symptomatic HD. In this investigation, we aimed to establish a robust method for measurements of the hypothalamic volume in MRI in order to determine whether the hypothalamic dysfunction in HD is associated with the volume of this region. Using T1-weighted imaging, we describe a reproducible delineation procedure to estimate the hypothalamic volume which was based on the same landmarks used in histologically processed postmortem hypothalamic tissue. Participants included 36 prodromal HD (pre-HD), 33 symptomatic HD (symp-HD) and 33 control participants who underwent MRI scanning at baseline and 18 months follow-up as part of the IMAGE-HD study. We found no evidence of cross-sectional or longitudinal changes between groups in hypothalamic volume. Our results suggest that hypothalamic pathology in HD is not associated with volume changes. 相似文献
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Hult S Soylu R Björklund T Belgardt BF Mauer J Brüning JC Kirik D Petersén Å 《Cell metabolism》2011,13(4):428-439
In Huntington's disease (HD), the mutant huntingtin protein is ubiquitously expressed. The disease was considered to be limited to the basal ganglia, but recent studies have suggested a more widespread pathology involving hypothalamic dysfunction. Here we tested the hypothesis that expression of mutant huntingtin in the hypothalamus causes metabolic abnormalities. First, we showed that bacterial artificial chromosome-mediated transgenic HD (BACHD) mice developed impaired glucose metabolism and pronounced insulin and leptin resistance. Selective hypothalamic expression of a short fragment of mutant huntingtin using adeno-associated viral vectors was sufficient to recapitulate these metabolic disturbances. Finally, selective hypothalamic inactivation of the mutant gene prevented the development of the metabolic phenotype in BACHD mice. Our findings establish a causal link between mutant huntingtin expression in the hypothalamus and metabolic dysfunction, and indicate that metabolic parameters are powerful readouts to assess therapies aimed at correcting dysfunction in HD by silencing huntingtin expression in the brain. 相似文献
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I. P. Grigor’ev D. E. Korzhevskii E. G. Sukhorukova V. V. Gusel’nikova O. V. Kirik 《Cell and Tissue Biology》2016,10(1):29-36
Marinesco bodies were discovered in substantia nigra neurons of human brain in 1902. The relationships between these intranuclear inclusions and the other structures of the cellular nucleus are still obscure. The aim of this study is to elucidate the morphological and cytochemical peculiarities of intranuclear ubiquitin-immunopositive bodies in the substantia nigra neurons of human brain and to evaluate the interconnections of these peculiarities with nucleolus by means of light microscopy, immunocytochemistry, and confocal laser microscopy. It is found that up to 20% of neurons in substantia nigra of human brain contain ubiquitin-immunopositive Marinesco bodies. These rounded structures are 1–8 μm—more often 2–4 μm—in diameter. Only one-third of them are tightly adjacent to the nucleolus. By a method of silver impregnation of argentophilic proteins associated with nucleolar organizer, the absence was shown of argentophilic proteins, which are characteristic for the nucleolus, in Marinesco bodies. Special ubiquitin-positive substantially smaller structures (less than 1 μm) are revealed in the neurons’ nuclei along with Marinesco bodies. These structures are probably the initial forms in the formation of Marinesco bodies. The existence of two types of ubiquitin-immunopositive intranuclear bodies is revealed by means of confocal microscopy: one has high intensity of immunofluorescence, and the other has low intensity. Heterogeneous distribution of immunopositive product is characteristic of the former. The presence of DNA in Marinesco bodies is detected by using SYTOX Green fluorescent dye. The absence of peripheral heterochromatin zone and weak susceptibility to toluidine blue together with the presence of DNA and the absence of argentophilic proteins suggests substantial structural and chemical differences between Marinesco bodies and nucleoli, which argues against the idea that the detected bodies are modified nucleoli. 相似文献
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Ricci GC De Souza-Kaneshima AM Felismino MF Mendes-Bonato AB Pagliarini MS Do Valle CB 《Journal of genetics》2011,90(2):289-294
A total of 44 accessions of Brachiaria decumbens were analysed for chromosome count and meiotic behaviour in order to identify potential progenitors for crosses. Among them,
15 accessions presented 2n = 18; 27 accessions, 2n = 36; and 2 accessions, 2n = 45 chromosomes. Among the diploid accessions, the rate of meiotic abnormalities was low, ranging from 0.82% to 7.93%. In
the 27 tetraploid accessions, the rate of meiotic abnormalities ranged from 18.41% to 65.83%. The most common meiotic abnormalities
were related to irregular chromosome segregation, but chromosome stickiness and abnormal cytokinesis were observed in low
frequency. All abnormalities can compromise pollen viability by generating unbalanced gametes. Based on the chromosome number
and meiotic stability, the present study indicates the apomictic tetraploid accessions that can act as male genitor to produce
interspecific hybrids with B. ruziziensis or intraspecific hybrids with recently artificially tetraploidized accessions. 相似文献
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Charitha Galva Viktor Kirik Jelmer J. Lindeboom Despoina Kaloriti David M. Rancour Patrick J. Hussey Sebastian Y. Bednarek David W. Ehrhardt John C. Sedbrook 《The Plant cell》2014,26(11):4409-4425
The microtubule plus-end tracking proteins (+TIPs) END BINDING1b (EB1b) and SPIRAL1 (SPR1) are required for normal cell expansion and organ growth. EB proteins are viewed as central regulators of +TIPs and cell polarity in animals; SPR1 homologs are specific to plants. To explore if EB1b and SPR1 fundamentally function together, we combined genetic, biochemical, and cell imaging approaches in Arabidopsis thaliana. We found that eb1b-2 spr1-6 double mutant roots exhibit substantially more severe polar expansion defects than either single mutant, undergoing right-looping growth and severe axial twisting instead of waving on tilted hard-agar surfaces. Protein interaction assays revealed that EB1b and SPR1 bind each other and tubulin heterodimers, which is suggestive of a microtubule loading mechanism. EB1b and SPR1 show antagonistic association with microtubules in vitro. Surprisingly, our combined analyses revealed that SPR1 can load onto microtubules and function independently of EB1 proteins, setting SPR1 apart from most studied +TIPs in animals and fungi. Moreover, we found that the severity of defects in microtubule dynamics in spr1 eb1b mutant hypocotyl cells correlated well with the severity of growth defects. These data indicate that SPR1 and EB1b have complex interactions as they load onto microtubule plus ends and direct polar cell expansion and organ growth in response to directional cues. 相似文献
10.
Hélène Hall Sandra Cuellar‐Baena Vladimir Denisov Deniz Kirik 《Journal of neurochemistry》2013,124(3):336-346
Choline acetyltransferase (ChAT) is the key enzyme for acetylcholine (ACh) synthesis and constitutes a reliable marker for the integrity of cholinergic neurons. Cortical ChAT activity is decreased in the brain of patients suffering from Alzheimer's and Parkinson's diseases. The standard method used to measure the activity of ChAT enzyme relies on a very sensitive radiometric assay, but can only be performed on post‐mortem tissue samples. Here, we demonstrate the possibility to monitor ACh synthesis in rat brain homogenates in real time using NMR spectroscopy. First, the experimental conditions of the radiometric assay were carefully adjusted to produce maximum ACh levels. This was important for translating the assay to NMR, which has a low intrinsic sensitivity. We then used 15N‐choline and a pulse sequence designed to filter proton polarization by nitrogen coupling before 1H‐NMR detection. ACh signal was resolved from choline signal and therefore it was possible to monitor ChAT‐mediated ACh synthesis selectively over time. We propose that the present approach using a labeled precursor to monitor the enzymatic synthesis of ACh in rat brain homogenates through real‐time NMR represents a useful tool to detect neurotransmitter synthesis. This method may be adapted to assess the state of the cholinergic system in the brain in vivo in a non‐invasive manner using NMR spectroscopic techniques. 相似文献