CDK13-related disorder, also known as congenital heart defects, dysmorphic facial features and intellectual developmental disorder (CHDFIDD) is associated with mutations in the CDK13 gene encoding transcription-regulating cyclin-dependent kinase 13 (CDK13). Here, we focused on the development of craniofacial structures and analyzed early embryonic stages in CHDFIDD mouse models, with one model comprising a hypomorphic mutation in Cdk13 and exhibiting cleft lip/palate, and another model comprising knockout of Cdk13, featuring a stronger phenotype including midfacial cleft. Cdk13 was found to be physiologically expressed at high levels in the mouse embryonic craniofacial structures, namely in the forebrain, nasal epithelium and maxillary mesenchyme. We also uncovered that Cdk13 deficiency leads to development of hypoplastic branches of the trigeminal nerve including the maxillary branch. Additionally, we detected significant changes in the expression levels of genes involved in neurogenesis (Ache, Dcx, Mef2c, Neurog1, Ntn1, Pou4f1) within the developing palatal shelves. These results, together with changes in the expression pattern of other key face-specific genes (Fgf8, Foxd1, Msx1, Meis2 and Shh) at early stages in Cdk13 mutant embryos, demonstrate a key role of CDK13 in the regulation of craniofacial morphogenesis.

• Klíčová slova
• Axons, CDK13, Craniofacial development, Neurite outgrowth, Orofacial clefts, Trigeminal ganglion,
• MeSH
• cyklin-dependentní kinasy metabolismus   genetika   MeSH
• embryo savčí metabolismus   MeSH
• embryonální vývoj * genetika   MeSH
• fenotyp MeSH
• lebka embryologie   patologie   MeSH
• mentální retardace genetika   MeSH
• modely nemocí na zvířatech * MeSH
• mutace genetika   MeSH
• myši MeSH
• nervus trigeminus embryologie   MeSH
• neurogeneze * genetika   MeSH
• obličej embryologie   abnormality   MeSH
• protein doublecortin MeSH
• rozštěp patra genetika   patologie   embryologie   MeSH
• rozštěp rtu genetika   patologie   embryologie   MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklin-dependentní kinasy MeSH
• Dcx protein, mouse MeSH Prohlížeč
• protein doublecortin MeSH

Hypothalamic Adult Neurogenesis (hAN) has been implicated in regulating energy homeostasis. Adult-generated neurons and adult Neural Stem Cells (aNSCs) in the hypothalamus control food intake and body weight. Conversely, diet-induced obesity (DIO) by high fat diets (HFD) exerts adverse influence on hAN. However, the effects of anti-obesity compounds on hAN are not known. To address this, we administered a lipidized analogue of an anti-obesity neuropeptide, Prolactin Releasing Peptide (PrRP), so-called LiPR, to mice. In the HFD context, LiPR rescued the survival of adult-born hypothalamic neurons and increased the number of aNSCs by reducing their activation. LiPR also rescued the reduction of immature hippocampal neurons and modulated calcium dynamics in iPSC-derived human neurons. In addition, some of these neurogenic effects were exerted by another anti-obesity compound, Liraglutide. These results show for the first time that anti-obesity neuropeptides influence adult neurogenesis and suggest that the neurogenic process can serve as a target of anti-obesity pharmacotherapy.

• Klíčová slova
• Adult neurogenesis, Anti-obesity peptides, Hypothalamus, Neural stem cells, Prolactin Releasing Peptide,
• MeSH
• hormon uvolňující prolaktin farmakologie   terapeutické užití   MeSH
• hypothalamus MeSH
• lidé MeSH
• myši MeSH
• neurogeneze MeSH
• neuropeptidy * MeSH
• obezita * farmakoterapie   MeSH
• tělesná hmotnost MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hormon uvolňující prolaktin MeSH
• neuropeptidy * MeSH

Generation of neurons in the embryonic neocortex is a balanced process of proliferation and differentiation of neuronal progenitor cells. Canonical Wnt signalling is crucial for expansion of radial glial cells in the ventricular zone and for differentiation of intermediate progenitors in the subventricular zone. We detected abundant expression of two transcrtiption factors mediating canonical Wnt signalling, Tcf7L1 and Tcf7L2, in the ventricular zone of the embryonic neocortex. Conditional knock-out analysis showed that Tcf7L2, but not Tcf7L1, is the principal Wnt mediator important for maintenance of progenitor cell identity in the ventricular zone. In the absence of Tcf7L2, the Wnt activity is reduced, ventricular zone markers Pax6 and Sox2 are downregulated and the neuroepithelial structure is severed due to the loss of apical adherens junctions. This results in decreased proliferation of radial glial cells, the reduced number of intermediate progenitors in the subventricular zone and hypoplastic forebrain. Our data show that canonical Wnt signalling, which is essential for determining the neuroepithelial character of the neocortical ventricular zone, is mediated by Tcf7L2.

• Klíčová slova
• Neocortex, Neurogenenesis, Tcf7L1, Tcf7L2, Wnt signalling,
• MeSH
• buněčná diferenciace genetika   MeSH
• chlorid-hydrogenuhličitanové antiportéry MeSH
• down regulace genetika   MeSH
• embryo savčí MeSH
• hipokampus cytologie   embryologie   MeSH
• mutace genetika   MeSH
• myši transgenní MeSH
• myši MeSH
• neokortex cytologie   embryologie   MeSH
• nervové kmenové buňky fyziologie   MeSH
• neurogeneze fyziologie   MeSH
• neuroglie MeSH
• neurony fyziologie   MeSH
• počet buněk MeSH
• proliferace buněk genetika   MeSH
• protein 2 podobný transkripčnímu faktoru 7 genetika   metabolismus   MeSH
• proteiny T-boxu metabolismus   MeSH
• proteiny Wnt metabolismus   MeSH
• retinální gangliové buňky fyziologie   MeSH
• signální transdukce genetika   MeSH
• transkripční faktory SOXB1 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chlorid-hydrogenuhličitanové antiportéry MeSH
• Eomes protein, mouse MeSH Prohlížeč
• protein 2 podobný transkripčnímu faktoru 7 MeSH
• proteiny T-boxu MeSH
• proteiny Wnt MeSH
• Sox2 protein, mouse MeSH Prohlížeč
• Tcf7l2 protein, mouse MeSH Prohlížeč
• transkripční faktory SOXB1 MeSH

The active role of biomaterials in the regeneration of tissues and their ability to modulate the behavior of stem cells in terms of their differentiation is highly advantageous. Here, polypyrrole, as a representantive of electro-conducting materials, is found to modulate the behavior of embryonic stem cells. Concretely, the aqueous extracts of polypyrrole induce neurogenesis within embryonic bodies formed from embryonic stem cells. This finding ledto an effort to determine the physiological cascade which is responsible for this effect. The polypyrrole modulates signaling pathways of Akt and ERK kinase through their phosphorylation. These effects are related to the presence of low-molecular-weight compounds present in aqueous polypyrrole extracts, determined by mass spectroscopy. The results show that consequences related to the modulation of stem cell differentiation must also be taken into account when polypyrrole is considered as a biomaterial.

• Klíčová slova
• biocompatibility, conducting polymer, neurogenesis, polypyrrole, stem cells,
• MeSH
• buněčná diferenciace účinky léků   genetika   MeSH
• buněčné linie MeSH
• embryoidní tělíska cytologie   účinky léků   MeSH
• exprese genu účinky léků   MeSH
• molekulární struktura MeSH
• myší embryonální kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• myši MeSH
• nervové kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• neurogeneze účinky léků   genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• polymery chemie   farmakologie   MeSH
• pyrroly chemie   farmakologie   MeSH
• transkripční faktor PAX6 genetika   MeSH
• transkripční faktory bHLH genetika   MeSH
• transkripční faktory SOXB1 genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Ascl1 protein, mouse MeSH Prohlížeč
• polymery MeSH
• polypyrrole MeSH Prohlížeč
• pyrroly MeSH
• transkripční faktor PAX6 MeSH
• transkripční faktory bHLH MeSH
• transkripční faktory SOXB1 MeSH

The inhibition of glycogen synthase kinase-3 (GSK-3) can induce neurogenesis, and the associated activation of Wnt/β-catenin signaling via GSK-3 inhibition may represent a means to promote motor function recovery following spinal cord injury (SCI) via increased astrocyte migration, reduced astrocyte apoptosis, and enhanced axonal growth. Herein, we assessed the effects of GSK-3 inhibition in vitro on the neurogenesis of ependymal stem/progenitor cells (epSPCs) resident in the mouse spinal cord and of human embryonic stem cell-derived neural progenitors (hESC-NPs) and human-induced pluripotent stem cell-derived neural progenitors (hiPSC-NPs) and in vivo on spinal cord tissue regeneration and motor activity after SCI. We report that the treatment of epSPCs and human pluripotent stem cell-derived neural progenitors (hPSC-NPs) with the GSK-3 inhibitor Ro3303544 activates β-catenin signaling and increases the expression of the bIII-tubulin neuronal marker; furthermore, the differentiation of Ro3303544-treated cells prompted an increase in the number of terminally differentiated neurons. Administration of a water-soluble, bioavailable form of this GSK-3 inhibitor (Ro3303544-Cl) in a severe SCI mouse model revealed the increased expression of bIII-tubulin in the injury epicenter. Treatment with Ro3303544-Cl increased survival of mature neuron types from the propriospinal tract (vGlut1, Parv) and raphe tract (5-HT), protein kinase C gamma-positive neurons, and GABAergic interneurons (GAD65/67) above the injury epicenter. Moreover, we observed higher numbers of newly born BrdU/DCX-positive neurons in Ro3303544-Cl-treated animal tissues, a reduced area delimited by astrocyte scar borders, and improved motor function. Based on this study, we believe that treating animals with epSPCs or hPSC-NPs in combination with Ro3303544-Cl deserves further investigation towards the development of a possible therapeutic strategy for SCI.

• Klíčová slova
• GSK3 inhibition, Spinal cord injury, axonal growth, neurogenesis, stem cells,
• MeSH
• kinasa 3 glykogensynthasy antagonisté a inhibitory   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• multipotentní kmenové buňky účinky léků   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neurogeneze účinky léků   MeSH
• poranění míchy farmakoterapie   enzymologie   MeSH
• transplantace kmenových buněk MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kinasa 3 glykogensynthasy MeSH

Effective treatment of patients with autism spectrum disorder (ASD) is still absent so far. Taurine exhibits therapeutic effects towards the autism-like behaviour in ASD model animals. Here, we determined the mechanism of taurine effect on hippocampal neurogenesis in genetically inbred BTBR T+ tf/J (BTBR) mice, a proposed model of ASD. In this ASD mouse model, we explored the effect of oral taurine supplementation on ASD-like behaviours in an open field test, elevated plus maze, marble burying test, self-grooming test, and three-chamber test. The mice were divided into four groups of normal controls (WT) and models (BTBR), who did or did not receive 6-week taurine supplementation in water (WT, WT+ Taurine, BTBR, and BTBR+Taurine). Neurogenesis-related effects were determined by Ki67 immunofluorescence staining. Western blot analysis was performed to detect the expression of phosphatase and tensin homologue deleted from chromosome 10 (PTEN)/mTOR/AKT pathway-associated proteins. Our results showed that taurine improved the autism-like behaviour, increased the proliferation of hippocampal cells, promoted PTEN expression, and reduced phosphorylation of mTOR and AKT in hippocampal tissue of the BTBR mice. In conclusion, taurine reduced the autism-like behaviour in partially inherited autism model mice, which may be associa-ted with improving the defective neural precursor cell proliferation and enhancing the PTEN-associated pathway in hippocampal tissue.

• Klíčová slova
• ASD, Ki67, PTEN, hippocampal neurogenesis, taurine,
• MeSH
• autistická porucha * metabolismus   farmakoterapie   MeSH
• chování zvířat účinky léků   MeSH
• fosfohydroláza PTEN * účinky léků   metabolismus   MeSH
• hipokampus * metabolismus   účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• neurogeneze * účinky léků   MeSH
• poruchy autistického spektra metabolismus   farmakoterapie   MeSH
• proliferace buněk účinky léků   MeSH
• protoonkogenní proteiny c-akt * účinky léků   metabolismus   MeSH
• signální transdukce * účinky léků   MeSH
• taurin * farmakologie   MeSH
• TOR serin-threoninkinasy * účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfohydroláza PTEN * MeSH
• mTOR protein, mouse MeSH Prohlížeč
• protoonkogenní proteiny c-akt * MeSH
• Pten protein, mouse MeSH Prohlížeč
• taurin * MeSH
• TOR serin-threoninkinasy * MeSH

Neurogenesis in the adult brain takes place in two neurogenic niches: the ventricular-subventricular zone (V-SVZ) and the subgranular zone. After differentiation, neural precursor cells (neuroblasts) have to move to an adequate position, a process known as neuronal migration. Some studies show that in Alzheimer's disease, the adult neurogenesis is impaired. Our main aim was to investigate some proteins involved both in the physiopathology of Alzheimer's disease and in the neuronal migration process using the APP/PS1 Alzheimer's mouse model. Progenitor migrating cells are accumulated in the V-SVZ of the APP/PS1 mice. Furthermore, we find an increase of Cdh1 levels and a decrease of Cdk5/p35 and cyclin B1, indicating that these cells have an alteration of the cell cycle, which triggers a senescence state. We find less cells in the rostral migratory stream and less mature neurons in the olfactory bulbs from APP/PS1 mice, leading to an impaired odour discriminatory ability compared with WT mice. Alzheimer's disease mice present a deficit in cell migration from V-SVZ due to a senescent phenotype. Therefore, these results can contribute to a new approach of Alzheimer's based on senolytic compounds or pro-neurogenic factors.

• Klíčová slova
• Beta-amyloid toxicity, Neurogenesis, Olfaction, Senescence, Subventricular zone,
• MeSH
• Alzheimerova nemoc * patologie   MeSH
• bulbus olfactorius patologie   MeSH
• myši MeSH
• nervové kmenové buňky * metabolismus   MeSH
• neurogeneze fyziologie   MeSH
• pohyb buněk MeSH
• ventriculi laterales metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Although histone acetylation is one of the most widely studied epigenetic modifications, there is still a lack of information regarding how the acetylome is regulated during brain development and pathophysiological processes. We demonstrate that the embryonic brain (E15) is characterized by an increase in H3K9 acetylation as well as decreases in the levels of HDAC1 and HDAC3. Moreover, experimental induction of H3K9 hyperacetylation led to the overexpression of NCAM in the embryonic cortex and depletion of Sox2 in the subventricular ependyma, which mimicked the differentiation processes. Inducing differentiation in HDAC1-deficient mouse ESCs resulted in early H3K9 deacetylation, Sox2 downregulation, and enhanced astrogliogenesis, whereas neuro-differentiation was almost suppressed. Neuro-differentiation of (wt) ESCs was characterized by H3K9 hyperacetylation that was associated with HDAC1 and HDAC3 depletion. Conversely, the hippocampi of schizophrenia-like animals showed H3K9 deacetylation that was regulated by an increase in both HDAC1 and HDAC3. The hippocampi of schizophrenia-like brains that were treated with the cannabinoid receptor-1 inverse antagonist AM251 expressed H3K9ac at the level observed in normal brains. Together, the results indicate that co-regulation of H3K9ac by HDAC1 and HDAC3 is important to both embryonic brain development and neuro-differentiation as well as the pathophysiology of a schizophrenia-like phenotype.

• Klíčová slova
• H3K9 acetylation, HDACs, acetylome, mouse neurogenesis, schizophrenia,
• MeSH
• acetylace MeSH
• antagonisté kanabinoidních receptorů farmakologie   MeSH
• antipsychotika farmakologie   MeSH
• časové faktory MeSH
• epigeneze genetická MeSH
• gestační stáří MeSH
• histondeacetylasa 1 antagonisté a inhibitory   genetika   metabolismus   MeSH
• histondeacetylasy genetika   metabolismus   MeSH
• histony metabolismus   MeSH
• inhibitory histondeacetylas farmakologie   MeSH
• methylazoxymethanolacetát MeSH
• modely nemocí na zvířatech MeSH
• molekuly buněčné adheze nervové genetika   metabolismus   MeSH
• mozek účinky léků   embryologie   enzymologie   patologie   MeSH
• myši inbrední C57BL MeSH
• neurogeneze * účinky léků   MeSH
• neurony účinky léků   enzymologie   patologie   MeSH
• posttranslační úpravy proteinů MeSH
• potkani Sprague-Dawley MeSH
• receptor kanabinoidní CB1 antagonisté a inhibitory   metabolismus   MeSH
• schizofrenie chemicky indukované   farmakoterapie   enzymologie   genetika   MeSH
• signální transdukce MeSH
• transkripční faktory SOXB1 genetika   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antagonisté kanabinoidních receptorů MeSH
• antipsychotika MeSH
• Cnr1 protein, rat MeSH Prohlížeč
• Hdac1 protein, mouse MeSH Prohlížeč
• Hdac1 protein, rat MeSH Prohlížeč
• histondeacetylasa 1 MeSH
• histondeacetylasy MeSH
• histone deacetylase 3 MeSH Prohlížeč
• histony MeSH
• inhibitory histondeacetylas MeSH
• methylazoxymethanolacetát MeSH
• molekuly buněčné adheze nervové MeSH
• receptor kanabinoidní CB1 MeSH
• Sox2 protein, mouse MeSH Prohlížeč
• transkripční faktory SOXB1 MeSH

Retinoic acid (RA) is able to induce the differentiation of embryonic stem cells into neuronal lineages. The mechanism of this effect is unknown but it has been evidenced to be dependent on the formation of floating spheroids called embryoid bodies. Results presented here show that the inhibition of phosphoinositide 3-kinase signaling pre-determines mouse embryonic stem cells to RA induced neurogenesis in monolayer culture with no need of embryoid bodies formation.

• MeSH
• 1-fosfatidylinositol-3-kinasa metabolismus   MeSH
• buněčné kultury MeSH
• chromony farmakologie   MeSH
• diferenciační antigeny genetika   metabolismus   MeSH
• embryonální kmenové buňky účinky léků   metabolismus   fyziologie   MeSH
• genetická transkripce MeSH
• inhibitory fosfoinositid-3-kinasy * MeSH
• kadheriny genetika   metabolismus   MeSH
• keratin-8 genetika   metabolismus   MeSH
• kultivované buňky MeSH
• luciferasy biosyntéza   genetika   MeSH
• molekuly buněčné adheze nervové genetika   metabolismus   MeSH
• morfoliny farmakologie   MeSH
• myši MeSH
• neurogeneze účinky léků   MeSH
• reportérové geny MeSH
• signální transdukce účinky léků   MeSH
• tretinoin farmakologie   MeSH
• tubulin genetika   metabolismus   MeSH
• tvar buňky účinky léků   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-fosfatidylinositol-3-kinasa MeSH
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one MeSH Prohlížeč
• beta3 tubulin, mouse MeSH Prohlížeč
• chromony MeSH
• diferenciační antigeny MeSH
• inhibitory fosfoinositid-3-kinasy * MeSH
• kadheriny MeSH
• keratin-8 MeSH
• luciferasy MeSH
• molekuly buněčné adheze nervové MeSH
• morfoliny MeSH
• tretinoin MeSH
• tubulin MeSH

The transplantation of stem cells may have a therapeutic effect on the pathogenesis and progression of neurodegenerative disorders. In the present study, we transplanted human mesenchymal stem cells (MSCs) into the lateral ventricle of a triple transgenic mouse model of Alzheimer's disease (3xTg-AD) at the age of eight months. We evaluated spatial reference and working memory after MSC treatment and the possible underlying mechanisms, such as the influence of transplanted MSCs on neurogenesis in the subventricular zone (SVZ) and the expression levels of a 56 kDa oligomer of amyloid β (Aβ*56), glutamine synthetase (GS) and glutamate transporters (Glutamate aspartate transporter (GLAST) and Glutamate transporter-1 (GLT-1)) in the entorhinal and prefrontal cortices and the hippocampus. At 14 months of age we observed the preservation of working memory in MSC-treated 3xTg-AD mice, suggesting that such preservation might be due to the protective effect of MSCs on GS levels and the considerable downregulation of Aβ*56 levels in the entorhinal cortex. These changes were observed six months after transplantation, accompanied by clusters of proliferating cells in the SVZ. Since the grafted cells did not survive for the whole experimental period, it is likely that the observed effects could have been transiently more pronounced at earlier time points than at six months after cell application.

• Klíčová slova
• Alzheimer’s disease, Aβ*56, mesenchymal stem cells, neurogenesis, working memory,
• MeSH
• Alzheimerova nemoc patologie   patofyziologie   terapie   MeSH
• amyloidní beta-protein metabolismus   MeSH
• bludiště - učení fyziologie   MeSH
• glutaminsynthetasa metabolismus   MeSH
• krátkodobá paměť fyziologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši transgenní MeSH
• myši MeSH
• neurogeneze MeSH
• proliferace buněk MeSH
• transplantace mezenchymálních kmenových buněk metody   MeSH
• ventriculi laterales cytologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amyloidní beta-protein MeSH
• glutaminsynthetasa MeSH