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

Impairments of N-methyl-D-aspartate receptor (NMDAR) activity have been implicated in several neuropsychiatric disorders, with pharmacological inhibition of NMDAR-mediated currents and associated neurobehavioral changes considered as a model of schizophrenia. We analyzed the effects of brief and long-term exposure of rat cortical cultures to the most prevalent endogenous modulators of NMDAR (kynurenic acid, pregnenolone sulfate, spermidine, and zinc) on neuronal viability, stimulation-induced release of glutamate, and dendritic morphology with synaptic density. Both, glutamate release and neuronal viability studies revealed no difference between the test and control groups. No differences were also observed in the number of dendritic branching and length, or density of synaptic connections and neuronal soma size. Comparison of the extent of dendritic projections and branching patterns, however, revealed enhanced distal arborization with the expansion of the dendritic area under prolonged treatment of cultures with physiological concentrations of NMDAR modulators, with differences reaching significance in spermidine and pregnenolone sulfate tests. Measurements of the density of glutamatergic synapses showed consistency across all neuronal groups, except those treated with pregnenolone sulfate, which showed a reduction of PSD-95-positive elements. Overall, our data suggest that constitutive glutamatergic activity mediated by NMDAR controls the dendritic field expansion and can influence the integrative properties of cortical neurons.

• MeSH
• glutamáty MeSH
• krysa rodu rattus MeSH
• neurony metabolismus   MeSH
• receptory N-methyl-D-aspartátu * metabolismus   MeSH
• signální transdukce MeSH
• spermidin * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The repetition of urea-based binding units within the receptor structure does not only lead to monomer properties multiplication. As confirmed by spectroscopic studies, UV-Vis and 1H-NMR in classical or competitive titration mode, the attachment to a carrier allocates the active moieties to mutual positions predetermining the function of the whole receptor molecule. Bivalent receptors form self-aggregates. Dendritic receptors with low dihydrogen phosphate loadings offer a cooperative complexation mode associated with a positive dendritic effect. In higher dihydrogen phosphate concentrations, the dendritic branches act independently and the binding mode changes to 1:1 anion: complexation site. Despite the anchoring, the dendritic receptors retain the superior efficiency and selectivity of a monomer, paving the way to recyclable receptors, desirable for economic and ecological reasons.

• MeSH
• magnetická rezonanční spektroskopie * MeSH
• molekulární modely MeSH
• sulfonamidy * MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Immune-mediated neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) are treatable neuropathies. Among individuals with diabetic neuropathy, it remains a challenge to identify those individuals who develop CIDP. Corneal confocal microscopy (CCM) has been shown to detect corneal nerve fiber loss and cellular infiltrates in the sub-basal layer of the cornea. The objective of the study was to determine whether CCM can distinguish diabetic neuropathy from CIDP and whether CCM can detect CIDP in persons with coexisting diabetes. METHODS: In this multicenter, case-control study, participants with CIDP (n = 55) with (n = 10) and without (n = 45) diabetes; participants with diabetes (n = 58) with (n = 28) and without (n = 30) diabetic neuropathy, and healthy controls (n = 58) underwent CCM. Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), and dendritic and non-dendritic cell density, with or without nerve fiber contact were quantified. RESULTS: Dendritic cell density in proximity to corneal nerve fibers was significantly higher in participants with CIDP with and without diabetes compared to participants with diabetic neuropathy and controls. CNFD, CNFL, and CNBD were equally reduced in participants with CIDP, diabetic neuropathy, and CIDP with diabetes. CONCLUSIONS: An increase in dendritic cell density identifies persons with CIDP. CCM may, therefore, be useful to differentiate inflammatory from non-inflammatory diabetic neuropathy.

• MeSH
• chronická zánětlivá demyelinizační polyneuropatie diagnóza   epidemiologie   MeSH
• dendrity patologie   MeSH
• diabetes mellitus 2. typu diagnóza   epidemiologie   MeSH
• diabetické neuropatie diagnóza   epidemiologie   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• konfokální mikroskopie metody   normy   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nervová vlákna patologie   MeSH
• rohovka patologie   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

In previous studies (Grécová et al., Eur J Neurosci 29:1921-1930, 2009; Bures et al., Eur J Neurosci 32:155-164, 2010), we demonstrated that after an early postnatal short noise exposure (8 min 125 dB, day 14) changes in the frequency tuning curves as well as changes in the coding of sound intensity are present in the inferior colliculus (IC) of adult rats. In this study, we analyze on the basis of the Golgi-Cox method the morphology of neurons in the IC, the medial geniculate body (MGB) and the auditory cortex (AC) of 3-month-old Long-Evans rats exposed to identical noise at postnatal day 14 and compare the results to littermate controls. In rats exposed to noise as pups, the mean total length of the neuronal tree was found to be larger in the external cortex and the central nucleus of the IC and in the ventral division of the MGB. In addition, the numerical density of dendritic spines was decreased on the branches of neurons in the ventral division of the MGB in noise-exposed animals. In the AC, the mean total length of the apical dendritic segments of pyramidal neurons was significantly shorter in noise-exposed rats, however, only slight differences with respect to controls were observed in the length of basal dendrites of pyramidal cells as well as in the neuronal trees of AC non-pyramidal neurons. The numerical density of dendritic spines on the branches of pyramidal AC neurons was lower in exposed rats than in controls. These findings demonstrate that early postnatal short noise exposure can induce permanent changes in the development of neurons in the central auditory system, which apparently represent morphological correlates of functional plasticity.

• MeSH
• akustická stimulace MeSH
• colliculus inferior růst a vývoj   patologie   MeSH
• dendritické trny patologie   MeSH
• hluk škodlivé účinky   MeSH
• metathalamus růst a vývoj   patologie   MeSH
• nervová síť patologie   MeSH
• neurony patologie   MeSH
• neuroplasticita MeSH
• novorozená zvířata MeSH
• potkani Long-Evans MeSH
• pyramidové buňky patologie   MeSH
• sluchová dráha patologie   MeSH
• sluchové korové centrum růst a vývoj   patologie   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Nepříznivé podmínky pro vývoj v perinatálním období (zátěž v podobě malnutrice, hypoxie) mají četné klinické důsledky, které jsou velmi dobře popsány i na základě experimentálních modelů. V mozku mezi ně patří ztráty neuronů v integračních okruzích mozkové kůry, redukce jejich dendritických větví, změny počtu synapsí i stupně myelinizace axonů. Tyto strukturální změny mají funkční důsledky, hlavně v oblasti kognitivních funkcí. Vývoj jedince v kriticky nepříznivých podmínkách však nemusí vždy znamenat jednoznačné poškození, zhoršení či ochuzení výsledného fenotypu. Může také znamenat vytvoření "alternativního fenotypu", který reprezentuje pro dané podmínky optimální přizpůsobení a který může být spojen i s lepšími vyhlídkami na přežití.

Perinatal distress (malnutrition, hypoxia etc.) has many clinical effects and it is well characterized in experimental animal models. Among the principal effects in the brain belongs the selective loss of neurons in integrative circuits of the cerebral cortex, reduction of dendritic branches and synapses or myelin impairment. Such structural changes have serious functional consequences, including impairment of cognitive functions. Development of an individual in such conditions does not always mean an impairment, harm or impoverishment of the resulting phenotype. It can represent formation of an "alternative phenotype" which enables optimal adjustment to given conditions and it can have better prospects for the survival.

• Klíčová slova
• vývoj fenotypu, postnatální zátěž,
• MeSH
• asfyxie novorozenců * komplikace   MeSH
• epigeneze genetická MeSH
• fenotyp MeSH
• fyziologická adaptace * MeSH
• kognice fyziologie   MeSH
• lidé MeSH
• maternální deprivace MeSH
• mozek * fyziologie   patofyziologie   růst a vývoj   MeSH
• novorozenec MeSH
• podvýživa komplikace   MeSH
• poruchy paměti etiologie   MeSH
• psychický stres MeSH
• psychosociální deprivace MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Dendrimers are well-defined macromolecules whose highly branched structure is reminiscent of many natural structures, such as trees, dendritic cells, neurons or the networks of kidneys and lungs. Nature has privileged such branched structures for increasing the efficiency of exchanges with the external medium; thus, the whole structure is of pivotal importance for these natural networks. On the contrary, it is generally believed that the properties of dendrimers are essentially related to their terminal groups, and that the internal structure plays the minor role of an 'innocent' scaffold. Here we show that such an assertion is misleading, using convergent information from biological data (human monocytes activation) and all-atom molecular dynamics simulations on seven families of dendrimers (13 compounds) that we have synthesized, possessing identical terminal groups, but different internal structures. This work demonstrates that the scaffold of nanodrugs strongly influences their properties, somewhat reminiscent of the backbone of proteins.

• MeSH
• aza sloučeniny chemie   farmakologie   MeSH
• biokompatibilní materiály chemie   farmakologie   MeSH
• bisfosfonáty chemie   farmakologie   MeSH
• dendrimery chemie   farmakologie   MeSH
• inhibitory kostní resorpce chemie   farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• monocyty účinky léků   MeSH
• nanočástice chemie   MeSH
• polylysin chemie   farmakologie   MeSH
• polypropyleny chemie   farmakologie   MeSH
• průtoková cytometrie MeSH
• silany chemie   farmakologie   MeSH
• simulace molekulární dynamiky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The structures of polysaccharides (PS) isolated from Lactobacillus rhamnosus LOCK 0900 and results from stimulation of mouse bone marrow-derived dendritic cells (BM-DC) and human embryonal kidney (HEK293) cells stably transfected with Toll-like receptors (TLR) upon exposure to these antigens were studied. L. rhamnosus LOCK 0900 produces PS that differ greatly in their structure. The polymer L900/2, with a high average molecular mass of 830 kDa, is a branched heteropolysaccharide with a unique repeating unit consisting of seven sugar residues and pyruvic acid, whereas L900/3 has a low average molecular mass of 18 kDa and contains a pentasaccharide repeating unit and phosphorus. Furthermore, we found that both described PS neither induce cytokine production and maturation of mouse BM-DC nor induce signaling through TLR2/TLR4 receptors. However, they differ profoundly in their abilities to modulate the BM-DC immune response to the well-characterized human isolate Lactobacillus plantarum WCFS1. Exposure to L900/2 enhanced interleukin-10 (IL-10) production induced by L. plantarum WCFS1, while in contrast, L900/3 enhanced the production of IL-12p70. We conclude that PS, probably due to their chemical features, are able to modulate the immune responses to third-party antigens. The ability to induce regulatory IL-10 by L900/2 opens up the possibility to use this PS in therapy of inflammatory conditions, such as inflammatory bowel disease, whereas L900/3 might be useful in reverting the antigen-dependent Th2-skewed immune responses in allergies.

• MeSH
• bakteriální polysacharidy chemie   imunologie   farmakologie   MeSH
• buňky kostní dřeně cytologie   MeSH
• cytokiny metabolismus   MeSH
• dendritické buňky účinky léků   imunologie   metabolismus   MeSH
• HEK293 buňky účinky léků   imunologie   MeSH
• imunologické faktory imunologie   farmakologie   MeSH
• konformace sacharidů MeSH
• Lacticaseibacillus rhamnosus chemie   imunologie   MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• molekulová hmotnost MeSH
• monosacharidy analýza   MeSH
• myši inbrední BALB C MeSH
• probiotika MeSH
• toll-like receptor 2 metabolismus   MeSH
• toll-like receptor 4 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Perinatální mozková hypoxie je známá svými klinickými důsledky a je i velmi dobře popsána na základě experimentálních modelů. Jejími důsledky jsou ztráty části neuronů integračních okruhů mozkové kůry, redukce jejich dendritických větví, změny počtu synapsí si i stupně myelinizace axonů. Tyto strukturální změny mají funkční důsledky, včetně změn kognitivních funkcí. Vývoj jedince v podmínkách hypoxie nemusí však vždy znamenat poškození, zhoršení či ochuzení výsledného fenotypu. Může také znamenat vytvoření „alternativního fenotypu", který reprezentuje optimální přizpůsobení daným podmínkám, které může být spojeno i s lepšími vyhlídkami na přežití.

Perinatal brain hypoxia has well known clinical effects and it is well characterized in experimental animal models. Among the principal effects belongs selective loss of neurons in integrative circuits of the cerebral cortex, reduction of dendritic branches and synapses or myelin impairment. Such structural changes have serious functional consequences, including impairment of cognitive functions. Develop- ment of an individual does not always mean an impairment, harm or impoverishment of the resulting phenotype. It can represent formation of an “alternative phenotype” which enables optimal adjustment to given conditions and it can have better prospects for the survival.

• Publikační typ
• abstrakt z konference MeSH

Utilization of metallic nanoparticles in various biotechnological and medical applications represents one of the most extensively investigated areas of the current materials science. These advanced applications require the appropriate chemical functionalization of the nanoparticles with organic molecules or their incorporation in suitable polymer matrices. The intensified interest in polymer nanocomposites with silver nanoparticles is due to the high antimicrobial effect of nanosilver as well as the unique characteristics of polymers which include their excellent structural uniformity, multivalency, high degree of branching, miscellaneous morphologies and architectures, and highly variable chemical composition. In this review, we explore several aspects of antimicrobial polymer silver nanocomposites, giving special focus to the critical analysis of the reported synthetic routes including their advantages, drawbacks, possible improvements, and real applicability in antibacterial and antifungal therapy. A special attention is given to "green" synthetic routes exploiting the biopolymeric matrix and to the methods allowing preparing magnetically controllable antimicrobial polymers for targeting to an active place. The controversial mechanism of the action of silver against bacteria, fungi and yeasts as well as perspectives and new applications of silver polymeric nanocomposites is also briefly discussed.

• MeSH
• antibakteriální látky chemická syntéza   farmakologie   MeSH
• dendrimery chemie   MeSH
• kovové nanočástice MeSH
• nanokompozity chemie   klasifikace   MeSH
• polymery chemie   MeSH
• sacharidy chemie   MeSH
• stříbro chemie   MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH