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.
- Klíčová slova
- Brain-derived neurotrophic factor (BDNF), Experimental autoimmune uveoretinitis (EAU), Müller cells, Retina, Visual stimulation,
- 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
- Názvy látek
- Bdnf protein, mouse MeSH Prohlížeč
- cytokiny MeSH
- mozkový neurotrofický faktor * MeSH
- vazoaktivní intestinální peptid 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.
- Klíčová slova
- Anti-NMDAR encephalitis, BDNF, Dendritic branching, Neuronal development, Synaptic proteins,
- 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
- Názvy látek
- gephyrin MeSH Prohlížeč
- membránové proteiny MeSH
- mozkový neurotrofický faktor * MeSH
- protein PSD-95 MeSH
- proteiny nervové tkáně MeSH
- receptory N-methyl-D-aspartátu * MeSH
- synaptofysin MeSH
- transportní proteiny MeSH
Neurotrophins are proteins included in development and functioning of various processed in mammalian organisms. They are important in early development but as well as during adulthood. Brain - derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been previously linked with many psychiatric disorders such as depression and addiction. Since during postnatal development, brain undergoes various functional and anatomical changes, we included preweaning environment enrichment (EE), since enrichment has been linked with improved function and development of the several brain structure such as hippocampus (HP), in which we monitored these changes. On the other hand, social isolation has been linked with depression and anxiety-like behavior, therefore postweaning social isolation has been added to this model as well and animal were exposed to this condition till adolescence. We examined if all these three factors had impact on BDNF and NGF levels during three phases of adolescence - postnatal days (PDs) 28, 35 and 45. Our results show that EE did not increase BDNF levels neither in control or MA exposed animals and these results are similar for both direct and indirect exposure. On the other side, social separation after weaning did reduce BDNF levels in comparison to standard housing animals but this effect was reversed by direct MA exposure. In terms of NGF, EE environment increased its levels only in indirectly exposed controls and MA animals during late adolescence. On the other hand, social separation increased NGF levels in majority of animals.
- MeSH
- hipokampus MeSH
- krysa rodu Rattus MeSH
- methamfetamin * farmakologie MeSH
- mozek metabolismus MeSH
- mozkový neurotrofický faktor * metabolismus MeSH
- nervový růstový faktor metabolismus MeSH
- zpožděný efekt prenatální expozice * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- methamfetamin * MeSH
- mozkový neurotrofický faktor * MeSH
- nervový růstový faktor MeSH
High-contrast visual stimulation promotes retinal regeneration and visual function, but the underlying mechanism is not fully understood. Here, we hypothesized that Müller cells (MCs), which express neurotrophins such as brain-derived neurotrophic factor (BDNF), could be key players in this retinal plasticity process. This hypothesis was tested by conducting in vivo and in vitro high-contrast stimulation of adult mice and MCs. Following stimulation, we examined the expression of BDNF and its inducible factor, VGF, in the retina and MCs. We also investigated the alterations in the expression of VGF, nuclear factor kappa B (NF-κB) and pro-inflammatory mediators in MCs, as well as their capacity to proliferate and develop a neurogenic or reactive gliosis phenotype after high-contrast stimulation and treatment with BDNF. Our results showed that high-contrast stimulation upregulated BDNF levels in MCs in vivo and in vitro. The additional BDNF treatment significantly augmented VGF production in MCs and their neuroprotective features, as evidenced by increased MC proliferation, neurodifferentiation, and decreased expression of the pro-inflammatory factors and the reactive gliosis marker GFAP. These results demonstrate that high-contrast stimulation activates the neurotrophic and neuroprotective properties of MCs, suggesting their possible direct involvement in retinal neuronal survival and improved functional outcomes in response to visual stimulation.
- Klíčová slova
- BDNF, Müller cells, NF-κB, VGF, high-contrast stimulation, neurodifferentiation, reactive gliosis,
- MeSH
- ependymální buňky * metabolismus MeSH
- fenotyp MeSH
- glióza metabolismus MeSH
- mozkový neurotrofický faktor * metabolismus MeSH
- myši MeSH
- retina metabolismus MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mozkový neurotrofický faktor * 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.
- Klíčová slova
- brain-derived neurotrophic factor, cytokines, dental pulp stem cell, multidirectional differentiation, nerve growth factor, neurotrophin-3. immunophenotype, vascular endothelial growth factor,
- 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
- Názvy látek
- cytokiny * MeSH
- mozkový neurotrofický faktor MeSH
- nervový růstový faktor MeSH
- neurotrofin 3 MeSH
- NTF3 protein, human MeSH Prohlížeč
- vaskulární endoteliální růstový faktor A MeSH
The aging of human populations, including those in Europe, is an indisputable fact. The challenge for the future is not simply prolonging human life at any cost or by any means but rather extending self-sufficiency and quality of life. Even in the most advanced societies, the eternal questions remain. Who will take care of the older generations? Will adult children's own circumstances be sufficient to support family members as they age? For a range of complex reasons, including socioeconomic conditions, adult children are often unable or unwilling to assume responsibility for the care of older family members. For this reason, it is imperative that aging adults maintain their independence and self-care for as long as possible. Movement is an important part of self-sufficiency. Moreover, movement has been shown to improve patients' clinical status. At a time when the coronavirus pandemic is disrupting the world, older people are among the most vulnerable. Our paper explores current knowledge and offers insights into the significant benefits of movement for the elderly, including improved immunity. We discuss the biochemical processes of aging and the counteractive effects of exercise and endogenous substances, such as vitamin D.
- Klíčová slova
- COVID-19, brain-derived neurotrophic factor (BDNF), exercises, geroscience, immunity, irisin, stress, vitamin D,
- MeSH
- COVID-19 imunologie patologie virologie MeSH
- cvičení * MeSH
- lidé MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- obezita patologie MeSH
- psychický stres MeSH
- sarkopenie patologie MeSH
- SARS-CoV-2 izolace a purifikace MeSH
- stárnutí * MeSH
- vitamin D aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mozkový neurotrofický faktor MeSH
- vitamin D MeSH
This study examined the effects of a nine-week intervention of four different high-intensity training modalities [high-intensity functional training (HIFT), high-intensity interval training (HIIT), high-intensity power training (HIPT), and high-intensity endurance training (HIET)] on the resting concentration of brain-derived neurotropic factor (BDNF). In addition, we evaluated the BDNF responses to Graded Exercise Test (GXT) and Wingate Anaerobic Test (WAnT) in men. Thirty-five healthy individuals with body mass index 25.55 ± 2.35 kg/m2 voluntarily participated in this study and were randomly assigned into four training groups. During nine-weeks they completed three exercise sessions per week for one-hour. BDNF was analyzed before and after a GXT and WAnT in two stages: (stage 0-before training and stage 9-after nine weeks of training). At stage 0, an increase in BDNF concentration was observed in HIFT (33%; p < 0.05), HIPT (36%; p < 0.05) and HIIT (38%; p < 0.05) after GXT. Even though HIET showed an increase in BDNF (10%) this was not statistically significant (p > 0.05). At stage 9, higher BDNF levels after GXT were seen only for the HIFT (30%; p < 0.05) and HIIT (18%; p < 0.05) groups. Reduction in BDNF levels were noted after the WAnT in stage 0 for HIFT (- 47%; p < 0.01), HIPT (- 49%; p < 0.001), HIET (- 18%; p < 0.05)], with no changes in the HIIT group (- 2%). At stage 9, BDNF was also reduced after WAnT, although these changes were lower compared to stage 0. The reduced level of BDNF was noted in the HIFT (- 28%; p < 0.05), and HIPT (- 19%;p < 0.05) groups. Additionally, all groups saw an improvement in VO2max (8%; p < 0.001), while BDNF was also correlated with lactate and minute ventilation and selected WAnT parameters. Our research has shown that resting values of BDNF after nine weeks of different forms of high-intensity training (HIT) have not changed or were reduced. Resting BDNF measured at 3th (before GXT at stage 9) and 6th day after long lasting HITs (before WAnT at stage 9) did not differed (before GXT), but in comparison to the resting value before WAnT at the baseline state, was lower in three groups. It appears that BDNF levels after one bout of exercise is depended on duration time, intensity and type of test/exercise.
- MeSH
- cvičení fyziologie MeSH
- dospělí MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- odpočinek fyziologie MeSH
- vysoce intenzivní intervalový trénink metody MeSH
- zátěžový test metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- BDNF protein, human MeSH Prohlížeč
- mozkový neurotrofický faktor MeSH
Neuroblastoma cell line SH-SY5Y, due to its capacity to differentiate into neurons, easy handling, and low cost, is a common experimental model to study molecular events leading to Alzheimer's disease (AD). However, it is prevalently used in its undifferentiated state, which does not resemble neurons affected by the disease. Here, we show that the expression and localization of amyloid-β protein precursor (AβPP), one of the key molecules involved in AD pathogenesis, is dramatically altered in SH-SY5Y cells fully differentiated by combined treatment with retinoic acid and BDNF. We show that insufficient differentiation of SH-SY5Y cells results in AβPP mislocalization.
- Klíčová slova
- Alzheimer’s disease, AβPP, SH-SY5Y, differentiation, super-resolution microscopy,
- MeSH
- Alzheimerova nemoc metabolismus MeSH
- amyloidový prekurzorový protein beta metabolismus MeSH
- biologické modely MeSH
- buněčná diferenciace fyziologie MeSH
- intravitální mikroskopie metody MeSH
- lidé MeSH
- mozkový neurotrofický faktor * metabolismus farmakologie MeSH
- nádorové buněčné linie MeSH
- neuroblastom MeSH
- neurony fyziologie MeSH
- oxidační stres MeSH
- proteolýza MeSH
- tretinoin * metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- Názvy látek
- amyloidový prekurzorový protein beta MeSH
- mozkový neurotrofický faktor * MeSH
- tretinoin * MeSH
Exercise therapy represents an important tool for the treatment of many neurological diseases, including cerebellar degenerations. In mouse models, exercise may decelerate the progression of gradual cerebellar degeneration via potent activation of neuroprotective pathways. However, whether exercise could also improve the condition in mice with already heavily damaged cerebella remains an open question. Here we aimed to explore this possibility, employing a mouse model with dramatic early-onset cerebellar degeneration, the Lurcher mice. The potential of forced physical activity and environmental enrichment (with the possibility of voluntary running) for improvement of behaviour and neuroplasticity was evaluated by a series of behavioural tests, measuring BDNF levels and using stereological histology techniques. Using advanced statistical analysis, we showed that while forced physical activity improved motor learning by ∼26 % in Lurcher mice and boosted BDNF levels in the diseased cerebellum by 57 %, an enriched environment partially alleviated some behavioural deficits related to behavioural disinhibition. Specifically, Lurcher mice exposed to the enriched environment evinced reduced open arm exploration in elevated plus maze test by 18 % and increased immobility almost 9-fold in the forced swim test. However, we must conclude that the overall beneficial effects were very mild and much less clear, compared to previously demonstrated effects in slowly-progressing cerebellar degenerations.
- Klíčová slova
- Behaviour, Cerebellar degeneration, Enriched environment, Forced physical activity, Lurcher mouse, motor functions,
- MeSH
- bydlení zvířat * MeSH
- chování zvířat fyziologie MeSH
- hra a hračky MeSH
- kondiční příprava zvířat fyziologie MeSH
- modely nemocí na zvířatech MeSH
- mozeček * metabolismus patologie MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- myši - mutanty neurologické MeSH
- myši MeSH
- neurodegenerativní nemoci * metabolismus patologie rehabilitace MeSH
- terapie cvičením MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Bdnf protein, mouse MeSH Prohlížeč
- mozkový neurotrofický faktor MeSH
Social defeat stress affects behavior and changes the expression of the genes underlying neuronal plasticity in the brain. The circadian clock regulates most neuronal processes in the brain, which results in daily variations of complex behavior, and any disturbance in circadian clock oscillations increases the risk of mood and cognitive disbalance. In this study, we assessed the effect of acute and repeated social defeat stress on Per2 and Nr1d1 expression in prefrontal cortexes, hippocampi, pineal glands, olfactory bulbs, cerebella, and pituitary glands. We also evaluated the effect of our experimental setting on levels of Bdnf and plasma corticosterone, two markers widely used to asses the impact of stress on mammalian physiology. Our data show that single and repeated social defeat stress upregulates the expression of both clock genes and Bdnf in all brain structures, and corticosterone in the blood. While the general pattern of Bdnf upregulation suggests higher sensitivity in the intruder group, the clock genes are induced more significantly in residents, especially by repeated stress sessions. Our work thus suggests that the model of stress-induced anxiety and depression should consider a group of residents because, for some parameters, they may respond more distinctively than intruders.LAY SUMMARYThe resident/intruder experimental paradigm affects the expression of clock genes Per2, Nr1d1and Bdnf in the brain structures and plasma corticosterone level. The induction of clock genes is evident in both experimental groups; however, it is more marked in residents. Together with the significant increase in Bdnf levels in the majority of brain structures and plasma corticosterone in residents, our data suggest that in the model of social defeat stress, the utility of an experimental group of residents could be contributive.
- Klíčová slova
- Clock genes, brain, brain-derived neurotrophic factor, corticosterone, rat, social defeat stress,
- MeSH
- kortikosteron MeSH
- krysa rodu Rattus MeSH
- mozek metabolismus MeSH
- mozkový neurotrofický faktor * genetika metabolismus MeSH
- potkani Wistar MeSH
- proteiny CLOCK * genetika metabolismus MeSH
- psychický stres * genetika MeSH
- sociální chování MeSH
- sociální porážka MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Bdnf protein, rat MeSH Prohlížeč
- Clock protein, rat MeSH Prohlížeč
- kortikosteron MeSH
- mozkový neurotrofický faktor * MeSH
- proteiny CLOCK * MeSH