A 9-bp deletion of the mtDNA is known as an anthropological marker of people with East-Asian origin. This 9-bp mtDNA deletion was analyzed in 1073 Hungarians with suspected mitochondrial disease and ...in 468 healthy control individuals. Fourteen cases with the 9-bp deletion were found in the cohort of mitochondrial patients, and one individual from 468 controls. In six cases the 9-bp deletion was present together with pathogenic major deletions in the mitochondrial genome. In one patient we found a frame shift mutation in the D-loop region, and in another family a pathogenic m.8322 A > G mutation in the tRNA
Lys
gene. Although the 9-bp deletion is common in the populations of the Pacific region and Asia, it is present in the Hungarian population as well. This 9-bp deletion may induce instability of the mtDNA and may provoke the introduction of other pathogenic mutations.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract The anti-apoptotic gene replacement could be an option in preventing hypoxia induced neuronal loss—necrosis and/or apoptosis. This intervention is however still controversial. In this paper, ...we tested the bcl-2 or bcl-XL anti-apoptotic gene transfers using an adenovirus vector in PC12 cells after hypoxia and re-oxygenation. Gene delivery results in a significant increase in both Bcl-2 and Bcl-XL proteins expression. Hypoxia (1 h)/re-oxygenation (4–48 h) have a detrimental effect upon cultured cells by inducing increased apoptosis by 30% compared to the controls. After hypoxia the compromised mitochondrial membrane function was detected by decreased tetramethyl-rhodamine-ethylester (TMRE) staining. Anti-apoptotic genes transferred 1 h after hypoxia, prevent the cell damage; the number of apoptotic cells has been reduced significantly and the gene transfers prevent mitochondrial membrane damage. Under normoxic conditions or following hypoxia the expression of plasticity protein, growth associated protein 43 (GAP-43) increased significantly by the gene treatment. We can conclude that anti-apoptotic gene transfers are not only cytoprotective as it is already documented before but these genes activate GAP-43 as well. This link on apoptotic signals and cell plasticity is a new finding.
Although much is known about the protective effect of acute estrogen therapy in cerebral ischemia, relatively little is known about its effect on functional outcome at different ages. The impact of ...age is, however, important on the efficacy of steroids in the central nervous system. We investigated whether a single dose of estradiol pre-treatment would be neuroprotective in young (4 months), middle-aged (9 months) and old (18 months) female gerbils following 10
min global brain ischemia. Apoptotic and necrotic cells were labelled and quantified in the affected hippocampus; exploratory activity, attention and memory functions were tested using open field, spontaneous alternation, novel object recognition and hole-board test. Age effect and treatment effect were analysed. High single dose (4
mg/kg b.w.) of estradiol pre-treatment exposed a marked neuroprotective effect against hippocampal cell loss in all age groups. In behavioural tests, however, age-related differences could be observed. In middle-aged and old animals the worsening in memory function following ischemia was more prominent compared to that in the young ones. In the Y-maze and the novel object recognition tests the middle-aged, in the hole-board test (investigating working memory and total time) the old gerbils had the worst functional outcome. Only reference memory in hole-board test did not change by age. Estrogen improved memory performances in all the tests at every age. We can conclude that age of experimental animals is a factor worsening the outcome following brain ischemia. A single-dose estrogen therapy prevents the lesion-induced behavioural dysfunctions and the hippocampal cell loss.
Winter supplementary feeding is widespread in large game management. As it is very expensive, it is important to know how essential this feeding may be for populations of game like red deer Cervus ...elaphus. Game managers typically observe only the disappearance of feed, but do not measure the consumption from the perspective of the animal, so the importance of feeding programs is often uncertain. During the winter of 2007–2008 we determined the consumption by red deer of two feed types (maize silage and apple pomace which is the residue from pressing apples) commonly offered at feeding plots in Hungary in two study areas. We simultaneously utilised two complementary methods: microhistological analysis of faeces and rumen content, and macroscopic observation of natural and artificially mixed food markers. Based on our analyses, 20 to 90% of the red deer (among different dates and measures) had eaten the supplementary food. However, the proportion of supplementary food in the red deer droppings collected in the immediate surroundings of the feeding plots was always very low (< 10%). This indicates that not every individual of the red deer population visits the feeders, or if does, eats a rather small amount of the provided food. Our data strongly suggests that supplementary food did not play a large role in the diet of the red deer individuals regularly visiting these sites. We emphasise that the mere observation that supplementary food regularly vanishes from the feeder does not necessarily mean that even one individual red deer has gained a significant biological advantage which would result in additional financial profit for the game manager later. Managers considering supplementary feeding should evaluate the quality of the forest area because the natural food supply can greatly influence the use of the feeding plots.
Permanent bilateral carotid occlusion is a well known cerebral hypoperfusion model in rats. The aim of our study was to investigate the different stages of vascular reaction by detecting changes in ...the extracellular martix proteins and to examine their relationship to angiogenesis after occlusion. Experiments were performed on adult male rats. Brain samples were investigated from day 1 to day 30 post-surgery. Immunohistochemical analysis was performed on the whole hippocampus and on the adjacent cortex in order to investigate extracellular martix proteins, such as the markers of dystroglycan complex (β-dystroglycan, α-dystrobrevin and utrophin) and a marker of basal lamina (laminin). The levels of the proteins were estimated by western blot analysis. Vascular density as well as blood–brain barrier permeability were studied on brain slices from the same regions. Our results showed altered laminin and β-dystroglycan immunoreactivity beginning 2
days after the onset of occlusion followed by an increased utrophin immunoreactivity without blood–brain barrier disruption 5
days later. By day 30 of hypoperfusion, when increased vascular density was detected, all changes returned to baseline levels. Western blot analysis showed significant differences in β-dystroglycan and utrophin expression. Our results indicate that the different stages of neovascularisation resulting from cerebral hypoperfusion can be well defined by the markers laminin, β-dystroglycan, and utrophin and that these markers are more likely to correlate with glio-vascular decoupling than does altered blood–brain barrier function.
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► Bilateral carotid occlusion in the rat. ► Cerebral hypoperfusion. ► Altered β-dystroglycan, utrophin and laminin immunoreactivity in the hippocampus and in the cortex. ► Altered nitric oxid synthase and vascular endothelial growth factor expression. ► Baseline β-dystroglycan, utrophin and laminin immunoreactivity. ► Increased vascular density in the examined regions in the brain.
The relevance of mitochondrial phosphate carrier (PiC), encoded by SLC25A3, in bioenergetics is well accepted. However, little is known about the mechanisms mediating the cellular impairments induced ...by pathological SLC25A3 variants. To this end, we investigated the pathogenicity of a novel compound heterozygous mutation in SLC25A3. First, each variant was modeled in yeast, revealing that substituting GSSAS for QIP within the fifth matrix loop is incompatible with survival on non-fermentable substrate, whereas the L200W variant is functionally neutral. Next, using skin fibroblasts from an individual expressing these variants and HeLa cells with varying degrees of PiC depletion, PiC loss of ∼60% was still compatible with uncompromised maximal oxidative phosphorylation (oxphos), whereas lower maximal oxphos was evident at ∼85% PiC depletion. Furthermore, intact mutant fibroblasts displayed suppressed mitochondrial bioenergetics consistent with a lower substrate availability rather than phosphate limitation. This was accompanied by slowed proliferation in glucose-replete medium; however, proliferation ceased when only mitochondrial substrate was provided. Both mutant fibroblasts and HeLa cells with 60% PiC loss showed a less interconnected mitochondrial network and a mitochondrial fusion defect that is not explained by altered abundance of OPA1 or MFN1/2 or relative amount of different OPA1 forms. Altogether these results indicate that PiC depletion may need to be profound (>85%) to substantially affect maximal oxphos and that pathogenesis associated with PiC depletion or loss of function may be independent of phosphate limitation when ATP requirements are not high.
Accumulation of cathepsin D immunoreactive lysosomes correlates with tissue pathology in sporadic Creutzfeldt-Jakob disease (CJD) brains. The C-to-T transition within exon 2 of the cathepsin D (CTSD) ...gene is associated with altered enzymatic activity. Possession of the TT genotype is a risk factor for variant CJD. To verify the association between the CTSD position 224T allele and the risk for and survival in sporadic and genetic CJD, we genotyped 540 sporadic, 101 genetic CJD, and 723 control individuals. Genotype data and duration of illness were compared using multiple logistic regression and Kruskal-Wallis test. Multivariate survival analysis was performed using Cox's regression model. The distribution of CTSD position 224 alleles was approximately the same in all groups. We observed a trend for shorter survival in sporadic CJD patients harboring the T allele at position 224 of the CTSD gene in particular in sporadic CJD patients with the prion protein gene position 129 MM genotype. We conclude that the CTSD position 224 polymorphism alone is not a significant risk or disease-modifying factor in sporadic or genetic CJD.
PURPOSETo investigate whether the single nucleotide polymorphisms (SNPs) of the LOXL1 gene associated with exfoliation syndrome (XFS) and exfoliative glaucoma (XFG) are different in XFS/XFG patients ...with and without cardiovascular disease (CVD); and to compare the allele frequencies in XFS/XFG with those in ischemic cerebrovascular disease (stroke), in the Hungarian population.
METHODSG153D and R141L allele frequencies were determined for 56 XFS/XFG patients (10 patients with and 45 without CVD, 1 patient unclassified), and for 189 patients with stroke.
RESULTSFor G153D the frequencies of guanine (G) and adenine (A) alleles were 71.4% and 28.6% in the ischemic stroke group, and 58.0% and 42.0% in XFS/XFG (χ test, P=0.008). The corresponding figures in XFS/XFG without CVD were 56.7% and 43.3%, and 60.0% and 40.0% in XFS/XFG with CVD (P=0.785). For R141L the frequencies of G and timidine (T) alleles were 68.2% and 31.7% in stroke patients, and 82.1% and 17.9% in XFS/XFG (P=0.004). No difference was seen for allele frequency distribution between XFS/XFG patients without and with CVD (84.4% and 15.6%; 80.0% and 20.0%, respectively, P=0.738).
CONCLUSIONSIn Hungarians, the frequency of G (risk) allele of G153D SNP was low in XFS/XFG. The frequency of G allele in R141L and G153D SNPs of the LOXL1 gene did not differ between XFS/XFG patients with and without CVD, but its frequency was different in XFS/XFG and ischemic stroke. These results suggest that the G allele in these SNPs has no direct role in the development of vascular diseases associated with XFS/XFG.
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