Pochopení vztahu mezi senzomotorickými proměnnými a exerkiny, které ovlivňují funkci mozku a kognici, nám umožňuje hlouběji porozumět biologickému procesu stárnutí. Hlavním cílem této studie bylo zjistit, jak silně jsou mozkový neurotrofický faktor (brain-derived neurotrophic factor, BDNF), irisin, svalová hmota a svalová síla asociovány s výsledky testů vybraných kognitivních funkcí u starších žen a jak dobře je predikují. Padesát sedm starších žen (průměrný věk 70,4 ± 4,1 roku) absolvovalo baterii neuropsychologických testů, měření izometrické dynamometrie a bioelektrické impedance. Hladiny v krevním séru sledovaných exerkinů byly stanoveny enzymatickým imunosorbentním testem (ELISA). Pro testování predikcí byly využity hierarchické vícenásobné regresní modely. Odhadli jsme, že rozptyl 46,1 % v krátkodobé paměti byl zapříčiněn hladinami BDNF v séru, přičemž druhým statisticky významným prediktorem byl věk (beta = –0,22; p = 0,030). Síla dolních končetin (lower limb strength, LLS) prokázala významnou prediktivní sílu jak u paměti – bezprostřední vybavení (beta = 0,39; p = 0,004), tak u paměti – oddálené vybavení (beta = 0,45; p = 0,001). Hladiny BDNF v séru byly významným prediktorem u oddáleného vybavení (beta = 0,29; p = 0,048). Přidání hladin BDNF do modelu prokázalo významné zvýšení jeho prediktivní síly o přibližně 5,6 % (p = 0,048) u paměti – oddálené vybavení. Index kosterní svalové hmoty (skeletal muscle index, SMI) a úroveň vzdělání byly významnými prediktory mentální flexibility. Byla zjištěna silná pozitivní asociace mezi hladinami BDNF, irisinem, svalovou silou a kognitivní funkcí, přičemž irisin a svalová síla jsou silnými prediktory hladin BDNF u starších žen. Studie byla realizována s podporou grantu Univerzity Karlovy – PRIMUS/19/HUM/012, Specifického vysokoškolského výzkumu SVV 260599, projektu COOPERATIO a Grantové agentury UK číslo grantu 268321. Korespondenční adresa: PhDr. Veronika Holá Katedra gymnastiky a úpolových sportů FTVS UK José Martího 269/31 162 52 Praha 6-Veleslavín e-mail: veronika.hola@ftvs.cuni.cz
Understanding the relationship between sensorimotor variables and exerkines related to brain function and cognition may help better understand biological ageing. The main aim of this study was to determine how strongly brain-derived neurotrophic factor (BDNF), irisin, muscle mass and muscle strength are associated and predict scores on selected cognitive domain tests in older women. Fifty seven older women (mean age 70.4 ± 4.1 years) underwent a battery of cognitive and psychological tests and measurements of isometric dynamometry and bioelectrical impedance. Serum exerkines levels were measured by enzyme-linked immunosorbent assay (ELISA). Hierarchical multiple regression models were used to test the predictions. We estimated that 46.1% of the variance in short-term memory was accounted for by serum BDNF levels, with age being the second statistically significant predictor (Beta = -0.22; p = 0.030). Lower limb strength (LLS) showed significant predictive power in both immediate (Beta = 0.39; p = 0.004) and delayed memory (Beta = 0.45; p = 0.001), serum BDNF levels were a significant predictor in delayed memory (Beta = 0.29; p = 0.048). Adding serum BDNF levels to the model showed a significant increase in predictive power of approximately 5.6% (p = 0.048) in delayed memory. Skeletal muscle index (SMI) and education level were significant predictors of mental flexibility. A strong positive association between BDNF levels, irisin, muscle strength, and cognitive function was found, with irisin and muscle strength being strong predictors of BDNF levels in older women.
- Klíčová slova
- irisin,
- MeSH
- fibronektinová doména typu III fyziologie MeSH
- kognice fyziologie MeSH
- kognitivní stárnutí * fyziologie MeSH
- lidé MeSH
- mozkový neurotrofický faktor krev MeSH
- neuropsychologické testy * statistika a číselné údaje MeSH
- paměť fyziologie MeSH
- prognóza MeSH
- průřezové studie MeSH
- regresní analýza MeSH
- senioři MeSH
- svalová atrofie etiologie MeSH
- svalová síla fyziologie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Maintaining healthy brain function during ageing is of great importance, especially for the self-sufficiency of older adults. The main aim of this study was to determine the effects of dance and martial arts on exerkines Brain Derived Neurotrophic Factor (BDNF) and irisin blood serum levels. METHODS: This randomized controlled trial examined the effects of dance and martial arts on serum Brain-Derived Neurotrophic Factor (BDNF) and irisin levels, as well as cognitive function, mood, and physical measures in older adults. Seventy-seven independently living older adults (mean age 70.3±3.8 years) were randomized into three groups: dance (DG), martial arts (MaG), and control (CG), followed over 12 weeks. Generalized linear models were used to assess the interventions' effects. RESULTS: There was a significant increase in BDNF levels in both the DG (1.8 ± 4.9, p < 0.05) and MaG (3.5 ± 6.3, p < 0.05), while CG experienced a decrease (-4.9 ± 8.2, p < 0.05). Between-group effects were significant for BDNF, with DG and MaG showing higher levels than CG (p < 0.05). No significant changes in irisin levels were found. Cognitive performance, particularly attention and mental flexibility (measured by the Trail Making Test A and B), significantly improved in the DG compared to CG (p < 0.05). Additionally, participants in DG showed improved mood based on the Geriatric Depression Scale (p < 0.05) compared to CG. Anthropometric T-scores were significantly associated with changes in irisin levels (p < 0.05) after intervention. CONCLUSION: The study found that dance and martial arts upregulated BDNF levels, with dance showing notable improvements in cognitive function and mood in older adults. Changes in anthropometric measures were linked to increased irisin levels. These findings suggest that both dance and martial arts may promote healthy brain function in aging populations. TRIAL REGISTRATION: NCT05363228.
- MeSH
- afekt MeSH
- bojové sporty * fyziologie MeSH
- fibronektiny * krev MeSH
- kognice * MeSH
- lidé MeSH
- mozkový neurotrofický faktor * krev MeSH
- senioři MeSH
- tanec * fyziologie MeSH
- tělesná výkonnost * fyziologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD). OBJECTIVE: We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered. METHODS: Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory. RESULTS: KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p = 0.038) and AD dementia (OR = 15.75, p = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (β = 0.42; p = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (β = 1.21, p = 0.027). CONCLUSIONS: Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits.
- MeSH
- alely MeSH
- Alzheimerova nemoc * genetika MeSH
- apolipoprotein E4 genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- genotyp MeSH
- intracelulární signální peptidy a proteiny genetika MeSH
- jednonukleotidový polymorfismus * genetika MeSH
- kognitivní dysfunkce * genetika MeSH
- lidé MeSH
- mozkový neurotrofický faktor genetika MeSH
- neuropsychologické testy MeSH
- paměť fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder characterized by IgG antibodies targeting NMDAR. The prevalence is remarkably higher in women and some develop the condition during pregnancy. While immunotherapies have shown good outcomes for pregnant mothers and their infants, the impact on early neurodevelopment remains elusive. This study investigates the effects of anti-NMDAR antibody on the development of primary cortical cultures. Anti-NMDAR antibody was administered to the cultures at day in vitro 5 for the following 5 days to assess dendritic branching and arbor complexity, and at day in vitro 14 for measuring the expression of brain-derived neurotrophic factor (BDNF) and synaptic proteins. Immature cultured neurons treated with anti-NMDAR antibody exhibited impaired dendritic branching and arbor complexity. Interestingly, BDNF expression was unaffected in mature neurons. Additionally, GluN1 expression, a mandatory NMDAR subunit, was significantly reduced, while no significant alterations were observed in PSD-95, gephyrin and synaptophysin expression. These findings shed light on the structural and synaptic impacts of anti-NMDAR antibody on immature neurons, providing evidence for their consequences in early neuronal development.
- MeSH
- dendrity * účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- membránové proteiny metabolismus imunologie MeSH
- mozkový neurotrofický faktor * metabolismus MeSH
- neurony * metabolismus účinky léků MeSH
- protein PSD-95 metabolismus MeSH
- proteiny nervové tkáně imunologie metabolismus MeSH
- receptory N-methyl-D-aspartátu * imunologie MeSH
- synaptofysin metabolismus MeSH
- transportní proteiny MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: To investigate the therapeutic potential of visual stimulation (VS) and BDNF in murine experimental autoimmune uveoretinitis (EAU). MAIN METHODS: Mice were immunized by subcutaneous injection of interphotoreceptor retinoid-binding protein in Freund's complete adjuvant and intravenous injection of pertussis toxin, and were then exposed to high-contrast VS 12 h/day (days 1-14 post-immunization). EAU severity was assessed by examining clinical score, visual acuity, inflammatory markers, and immune cells in the retina. The transcriptome of activated retinal cells was determined by RNA-seq using RNA immunoprecipitated in complex with phosphorylated ribosomal protein S6. The retinal levels of protein products of relevant upregulated genes were quantified. The effect of BDNF on EAU was tested in unstimulated mice by its daily topical ocular administration (days 8-14 post-immunization). KEY FINDINGS: VS attenuated EAU development and decreased the expression of pro-inflammatory cytokines/chemokines and numbers of immune cells in the retina (n = 10-20 eyes/group for each analysis). In activated retinal cells of control mice (n = 30 eyes/group), VS upregulated genes encoding immunomodulatory neuropeptides, of which BDNF and vasoactive intestinal peptide (VIP) also showed increased mRNA and protein levels in the retina of VS-treated EAU mice (n = 6-10 eyes/group for each analysis). In unstimulated EAU mice, BDNF treatment mimicked the protective effects of VS by modulating the inflammatory and stem cell properties of Müller cells (n = 5 eyes/group for each analysis). SIGNIFICANCE: VS effectively suppresses EAU, at least through enhancing retinal levels of anti-inflammatory and neuroprotective factors, VIP and BDNF. Our findings also suggest BDNF as a promising therapeutic agent for uveitis treatment.
- MeSH
- autoimunitní nemoci * imunologie metabolismus MeSH
- cytokiny metabolismus MeSH
- modely nemocí na zvířatech MeSH
- mozkový neurotrofický faktor * metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- retina metabolismus účinky léků MeSH
- retinitida * farmakoterapie prevence a kontrola imunologie MeSH
- uveitida * metabolismus farmakoterapie imunologie MeSH
- vazoaktivní intestinální peptid farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Mild behavioral impairment (MBI) has been commonly reported in early Alzheimer's disease (AD) but rarely using biomarker-defined samples. It is also unclear whether genetic polymorphisms influence MBI in such individuals. We thus aimed to examine the association between the cognitive status of participants (amnestic mild cognitive impairment (aMCI-AD) vs cognitively normal (CN) older adults) and MBI severity. Within aMCI-AD, we further examined the association between APOE and BDNF risk genetic polymorphisms and MBI severity. METHODS: We included 62 aMCI-AD participants and 50 CN older adults from the Czech Brain Aging Study. The participants underwent neurological, comprehensive neuropsychological examination, APOE and BDNF genotyping, and magnetic resonance imaging. MBI was diagnosed with the Mild Behavioral Impairment Checklist (MBI-C), and the diagnosis was based on the MBI-C total score ≥ 7. Additionally, self-report instruments for anxiety (the Beck Anxiety Inventory) and depressive symptoms (the Geriatric Depression Scale-15) were administered. The participants were stratified based on the presence of at least one risk allele in genes for APOE (i.e., e4 carriers and non-carriers) and BDNF (i.e., Met carriers and non-carriers). We used linear regressions to examine the associations. RESULTS: MBI was present in 48.4% of the aMCI-AD individuals. Compared to the CN, aMCI-AD was associated with more affective, apathy, and impulse dyscontrol but not social inappropriateness or psychotic symptoms. Furthermore, aMCI-AD was related to more depressive but not anxiety symptoms on self-report measures. Within the aMCI-AD, there were no associations between APOE e4 and BDNF Met and MBI-C severity. However, a positive association between Met carriership and self-reported anxiety appeared. CONCLUSIONS: MBI is frequent in aMCI-AD and related to more severe affective, apathy, and impulse dyscontrol symptoms. APOE and BDNF polymorphisms were not associated with MBI severity separately; however, their combined effect warrants further investigation.
- MeSH
- Alzheimerova nemoc * diagnostické zobrazování epidemiologie genetika MeSH
- apolipoproteiny E genetika MeSH
- genotyp MeSH
- kognitivní dysfunkce * diagnostické zobrazování epidemiologie genetika MeSH
- lidé MeSH
- mozkový neurotrofický faktor genetika MeSH
- neuropsychologické testy MeSH
- polymorfismus genetický genetika MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- Alzheimerova nemoc * genetika patofyziologie patologie MeSH
- apolipoproteiny E MeSH
- epigenomika MeSH
- kognice MeSH
- kognitivní poruchy etiologie genetika patofyziologie patologie MeSH
- lidé MeSH
- mozkový neurotrofický faktor MeSH
- polymorfismus genetický * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2'-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.
Inflammation and immunity belong to the main factors influencing tumor growth. In this study, we attempted to identify a profile of biomarkers associated with gliomas. We found decreased serum levels of sTREM-1 (soluble triggering receptor expressed on myelocytes) and increased levels of IL-10 in all grades of glioma patients in comparison with healthy controls (sTREM-1: grade II: p=0.0051, grade III: p=0.02, grade IV: p=0.01; IL-10: grade II: p=0.0017, grade III: p=0.03, grade IV: p=0.007). However, we did not find any combination of tested markers with good sensitivity and specificity in grades II and III of glioma patients to discriminate them from healthy controls. In grade IV glioma patients, two sets of markers showed promising results in distinguishing patients from healthy people. For the first set consisting of four selected markers, sTREM-1, sHLA-G, BDNF, and IL-13, the ROC curves indicate a good discriminatory capability for glioblastoma patients (AUC=0.9510). The best discriminatory capability for glioblastoma patients (AUC=0.9534) was found for the second set consisting of three selected markers sTREM-1, sHLA-G, and BDNF with 79.2% sensitivity and 94.1% specificity.
- MeSH
- biologické markery MeSH
- glioblastom * MeSH
- gliom * MeSH
- interleukin-10 MeSH
- lidé MeSH
- mozkový neurotrofický faktor MeSH
- receptor TREM-1 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: By measuring the extent of cytokines secreted by human dental pulp stem cells (hDPSCs) from passages 2 through 10, the optimal passage of hDPSCs was determined. This offers a potential theoretical basis for the treatment of neurological disorders. METHOD: After isolation and culture of hDPSCs from human teeth, the morphological features of the cells were observed under an inverted microscope. hDPSCs were identified by their immunophenotypes and their multiple differentiation capability. Cytokine concentrations secreted in the supernatants at passages 2-10 were detected by ELISA. RESULTS: hDPSCs were viewed as fusiform or polygonal in shape, with a bulging cell body, homogenized cytoplasm, and a clear nucleus. Moreover, they could differentiate into neuroblasts in vitro. hDPSCs at passage 3 were positive for CD29 (91.5%), CD73 (94.8%) and CD90 (96.7%), but negative for the hematopoietic markers CD34 (0.13%). ELISA results showed that hDPSCs at passage 3 had the highest secretion levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF), with the highest secretion level of Neurotrophin-3 (NT-3) being at passage 2. CONCLUSION: hDPSCs have steady biological features of stem cells and exhibit optimal proliferation potential. hDPSCs at different passages have different capacities in the secretion of VEGF, BDNF, NGF, and NT-3. In conclusion cytokines secreted by hDPSCs may prove to be appropriate in the treatment of neurological diseases.
- MeSH
- buněčná diferenciace * MeSH
- cytokiny * metabolismus MeSH
- kmenové buňky * metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- nervový růstový faktor metabolismus MeSH
- neurotrofin 3 metabolismus MeSH
- proliferace buněk MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zubní dřeň cytologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
