Clinical studies consistently report structural impairments (i.e.: ventricular enlargement, decreased volume of anterior cingulate cortex or hippocampus) and functional abnormalities including changes in regional cerebral blood flow in individuals suffering from schizophrenia, which can be evaluated by magnetic resonance imaging (MRI) techniques. The aim of this study was to assess cerebral blood perfusion in several schizophrenia-related brain regions using Arterial Spin Labelling MRI (ASL MRI, 9.4 T Bruker BioSpec 94/30USR scanner) in rats. In this study, prenatal exposure to methylazoxymethanol acetate (MAM, 22 mg/kg) at gestational day (GD) 17 and the perinatal treatment with Δ-9-tetrahydrocannabinol (THC, 5 mg/kg) from GD15 to postnatal day 9 elicited behavioral deficits consistent with schizophrenia-like phenotype, which is in agreement with the neurodevelopmental hypothesis of schizophrenia. In MAM exposed rats a significant enlargement of lateral ventricles and perfusion changes (i.e.: increased blood perfusion in the circle of Willis and sensorimotor cortex and decreased perfusion in hippocampus) were detected. On the other hand, the THC perinatally exposed rats did not show differences in the cerebral blood perfusion in any region of interest. These results suggest that although both pre/perinatal insults showed some of the schizophrenia-like deficits, these are not strictly related to distinct hemodynamic features.
- MeSH
- circulus arteriosus Willisi diagnostické zobrazování účinky léků embryologie MeSH
- hipokampus krevní zásobení diagnostické zobrazování účinky léků embryologie MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- magnetická rezonanční angiografie metody MeSH
- methylazoxymethanolacetát toxicita MeSH
- modely nemocí na zvířatech MeSH
- mozkový krevní oběh účinky léků MeSH
- neurogeneze účinky léků MeSH
- schizofrenie chemicky indukované diagnóza MeSH
- senzorimotorický kortex krevní zásobení diagnostické zobrazování účinky léků embryologie MeSH
- techniky pozorování chování MeSH
- těhotenství MeSH
- tetrahydrokanabinol toxicita MeSH
- zpožděný efekt prenatální expozice chemicky indukované diagnostické zobrazování MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- methylazoxymethanolacetát MeSH
- tetrahydrokanabinol 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 effect of ethanol on the structural development of the central nervous system was studied in offspring of Wistar rats, drinking 20 % ethanol during pregnancy and till the 28th day of their postnatal life. The structural changes in the hippocampus and dentate gyrus were analyzed at the age of 18, 35 and 90 days. A lower width of pyramidal and granular cell layers, cell extinction and fragmentation of numerous nuclei were found in all experimental animals compared to control animals. The extent of neural cell loss was similar in all monitored areas and in all age groups. At the age of 18 and 35 days, the degenerating cells were observed in the CA1 and CA3 area of the hippocampus and in the ventral and dorsal blade of the dentate gyrus. Numerous glial cells replaced the neuronal population of this region. Some degenerating cells with fragmented nuclei were observed at the age of 90 days. Our experiments confirmed the vulnerability of the developing central nervous system by ethanol intake during the perinatal period and revealed a long-lasting degeneration process in the hippocampus and dentate gyrus.
- MeSH
- analýza rozptylu MeSH
- ethanol toxicita MeSH
- gyrus dentatus účinky léků embryologie růst a vývoj patologie MeSH
- hipokampus účinky léků embryologie růst a vývoj patologie MeSH
- krysa rodu Rattus MeSH
- látky tlumící činnost CNS toxicita MeSH
- longitudinální studie MeSH
- neparametrická statistika MeSH
- neurony účinky léků patologie MeSH
- pití alkoholu patologie MeSH
- potkani Wistar MeSH
- těhotenství MeSH
- velikost orgánu MeSH
- zpožděný efekt prenatální expozice patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ethanol MeSH
- látky tlumící činnost CNS MeSH
The study deals with neurotoxic effects of alcohol on the CNS of laboratory rats in the prenatal period. The aim of the experiment is to analyse structure of the hippocampus after the prenatal exposure to alcohol and to identify the most vulnerable hippocampal regions. Pregnant Wistar rats of our own breed received alcohol (2 g per 100 g of body i.p.) each day since the first to the last day of pregnancy. Since the birth till the age of 34 days offsprings were kept together with their mother and were not exposed to alcohol. At the age of 35 days animals were perfused under the deep thiopental anaesthesia with buffered solution of paraformaldehyde. In the CA1 area of the hippocampus groups of degenerating cells were observed. In the CA3 area degenerating cells were also found. Some cells with fine granulated karyons were identified, which were accompanied with high number of glial cells. Our results demonstrate the neurotoxic effects of alcohol and the high vulnerability of the developing CNS. Remarkable is the observation of the high number of dying cells 35 days after the last exposition to alcohol. It suggests a long-term process of neuronal circuit remodelling in the juvenile tissue, probably triggered by apoptosis. The identification of cells with fine granulated karyons indicates the role of apoptotic mechanism in the cell death.
- MeSH
- ethanol farmakologie MeSH
- hipokampus účinky léků embryologie MeSH
- krysa rodu Rattus MeSH
- neurony účinky léků patologie MeSH
- plod účinky léků MeSH
- potkani Wistar MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ethanol MeSH
beta-Catenin plays a pivotal role in Wnt signaling during embryogenesis and is a component of adherens junctions. Since targeted disruption of the beta-catenin gene is lethal at gastrulation we have used a D6-Cre mouse line for conditional inactivation of beta-catenin in the mouse cerebral cortex and hippocampus after embryonic day (E) 10.5. In D6-Cre floxed beta-catenin mice, hippocampal CA1-CA2 fields are disrupted in similar manner as in Wnt-3a and LEF-1 mutants. The cortex of D6-Cre floxed beta-catenin mutants is strongly affected which contrasts with the normal cortex observed in Wnt-3a and LEF-1 mutants. Severe abnormalities in the organization of the neuroepithelium are observed that include disrupted interkinetic nuclear migration, loss of adherens junctions, impaired radial migration of neurons toward superficial layers and decreased cell proliferation after E15.5. At newborn stage, a premature disassembly of the radial glial scaffold and increased numbers of astrocytes are found in the cortex.
- MeSH
- beta-katenin MeSH
- cytoskeletální proteiny genetika metabolismus MeSH
- DNA vazebné proteiny metabolismus MeSH
- hipokampus embryologie růst a vývoj MeSH
- hybridizace in situ MeSH
- imunohistochemie MeSH
- mitóza MeSH
- mozková kůra embryologie růst a vývoj MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- neuroglie metabolismus MeSH
- neurony metabolismus MeSH
- pohyb buněk * MeSH
- trans-aktivátory genetika metabolismus MeSH
- transkripční faktory genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- beta-katenin MeSH
- CTNNB1 protein, mouse MeSH Prohlížeč
- cytoskeletální proteiny MeSH
- DNA vazebné proteiny MeSH
- trans-aktivátory MeSH
- transkripční faktory MeSH
The effect of lead acetate administration during perinatal (1. prenatal, 2. prenatal and suckling period, 3. prenatal + suckling period + 4 weeks after weaning) development in combination with ethanol was investigated in Wistar rats at the age of 12 weeks on open-field behaviour and auditory startle response. Lead intoxication has on the investigated behavioural parameters the most pronouncing effect when applied during the days 5-15 of pregnancy.
- MeSH
- chování zvířat účinky léků MeSH
- dlouhodobá potenciace účinky léků MeSH
- embryonální a fetální vývoj účinky léků MeSH
- ethanol toxicita MeSH
- hipokampus účinky léků embryologie metabolismus MeSH
- krysa rodu Rattus MeSH
- olovo toxicita MeSH
- potkani Wistar MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ethanol MeSH
- olovo MeSH
Live neuronal suspensions, prepared from the hippocampal region of donors aged 20 embryonal days, were observed in the Nomarski Differential Interference Contrast. Many neurones displayed profiles, resembling dendrites or axons and both principal hippocampal neurones (pyramidal and granular cells) were identified. For transplantation studies, donors of a younger embryonal age are thus recommended.
- MeSH
- axony fyziologie MeSH
- časové faktory MeSH
- dendrity fyziologie MeSH
- embryonální a fetální vývoj fyziologie MeSH
- hipokampus cytologie embryologie MeSH
- krysa rodu Rattus MeSH
- neurony fyziologie transplantace MeSH
- plod inervace MeSH
- těhotenství MeSH
- transplantace fetální tkáně normy MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
