Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic and worldwide. Previous studies have demonstrated the adverse effects of maternal drug abuse. However, the father's contribution as a parent and donor of the half genetic information is unclear. The present study aimed to examine the effect of paternal MA exposure on behavioral development and locomotor activity in rat offspring. MA was administrated subcutaneously for 30 days at a dose of 5 mg/kg to adult male rats. The impact of paternal MA exposure on rat pups was investigated using behavioral tests during development and locomotor activity tests in adulthood. Prior to testing, adult offspring were exposed to an acute challenge dose of MA (1 mg/kg) to examine the possible sensitizing effect of the paternal treatment. Our results found no significant differences in behavioral development or locomotor activity in adulthood of offspring linked to paternal MA application. These results differ from the effects induced by maternal MA application. Further, our results demonstrated a significant increase in locomotor activity on the Laboras test after acute MA application. When comparing sex differences, females showed more activity than males in adulthood, whereas males were more active during development.
- MeSH
- chování zvířat účinky léků MeSH
- krysa rodu Rattus MeSH
- lokomoce účinky léků MeSH
- methamfetamin toxicita MeSH
- metoda rotující tyčky MeSH
- otec - expozice noxám * MeSH
- pohlavní dimorfismus MeSH
- polohový reflex účinky léků MeSH
- potkani Wistar MeSH
- senzorimotorický kortex účinky léků růst a vývoj MeSH
- sexuální faktory MeSH
- stimulanty centrálního nervového systému toxicita MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- methamfetamin MeSH
- stimulanty centrálního nervového systému MeSH
For many degenerative cerebellar diseases, currently, no effective treatment that would substantially restore cerebellar functions is available. Neurotransplantation could be a promising therapy for such cases. Nevertheless, there are still severe limitations for routine clinical use. The aim of the work was to assess volume and morphology and functional impact on motor skills of an embryonic cerebellar graft injected in the form of cell suspension in Lurcher mutant and wild-type mice of the B6CBA and C3H strains after a 6-month survival period. The grafts survived in the majority of the mice. In both B6CBA and C3H Lurcher mice, most of the grafts were strictly delimited with no tendency to invade the host cerebellum, while in wild-type mice, graft-derived Purkinje cells colonized the host's cerebellum. In C3H Lurcher mice, but not in B6CBA Lurchers, the grafts had smaller volume than in their wild-type counterparts. C3H wild-type mice had significantly larger grafts than B6CBA wild-type mice. No positive effect of the transplantation on performance in the rotarod test was observed. The findings suggest that the niche of the Lurcher mutant cerebellum has a negative impact on integration of grafted cells. This factor seems to be limiting for specific functional effects of the transplantation therapy in this mouse model of cerebellar degeneration.
- Klíčová slova
- Cerebellar degeneration, Cerebellum, Lurcher mouse, Purkinje cell, Transplantation,
- MeSH
- druhová specificita MeSH
- longitudinální studie MeSH
- metoda rotující tyčky MeSH
- modely nemocí na zvířatech MeSH
- motorické dovednosti MeSH
- mozeček embryologie patologie transplantace MeSH
- myši - mutanty neurologické MeSH
- myši inbrední C3H MeSH
- myši inbrední CBA MeSH
- myši transgenní MeSH
- nemoci mozečku patologie patofyziologie terapie MeSH
- neurodegenerativní nemoci patologie patofyziologie terapie MeSH
- přežívání štěpu * fyziologie MeSH
- transplantace mozkové tkáně * MeSH
- zelené fluorescenční proteiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- enhanced green fluorescent protein MeSH Prohlížeč
- zelené fluorescenční proteiny MeSH
Methamphetamine (MA) is an addictive psychostimulant with significant potential for abuse. Previous rat studies have demonstrated that MA use during pregnancy impairs maternal behavior and induced delayed development of affected pups. The offspring of drug-addictive mothers were often neglected and exposed to neonatal stressors. The present study therefore examines the effect of perinatal stressors combined with exposure to prenatal MA on the development of pups and maternal behavior. Dams were divided into three groups according to drug treatment during pregnancy: controls (C); saline (SA, s.c., 1 ml/kg); MA (s.c., 5 mg/ml/kg). Litters were divided into four groups according to postnatal stressors: controls (N); maternal separation (S); maternal cold-water stress (W); maternal separation plus cold-water stress (SW). The pup-retrieval test showed differences among postnatally stressed mothers and non-stressed controls. The righting reflex on a surface revealed delayed development of pups prenatally exposed to MA/SA and postnatal stress. Negative geotaxis and Rotarod results confirmed that the MA group was the most affected. Overall, our data suggests that a combination of perinatal stress and prenatal MA can have a detrimental effect on maternal behavior as well as on the sensorimotor development of pups. However, MA exposure during pregnancy seems to be the decisive factor for impairment.
- MeSH
- krysa rodu Rattus MeSH
- maternální deprivace MeSH
- mateřské chování účinky léků fyziologie psychologie MeSH
- methamfetamin toxicita MeSH
- metoda rotující tyčky metody psychologie MeSH
- náhodné rozdělení MeSH
- novorozená zvířata MeSH
- poruchy spojené s užíváním psychoaktivních látek komplikace patofyziologie psychologie MeSH
- potkani Wistar MeSH
- psychický stres komplikace patofyziologie psychologie MeSH
- psychomotorický výkon účinky léků fyziologie MeSH
- stimulanty centrálního nervového systému toxicita MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice chemicky indukované patofyziologie psychologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- methamfetamin MeSH
- stimulanty centrálního nervového systému MeSH
Diamond-Blackfan anaemia is a rare disease caused by insufficient expression of ribosomal proteins and is characterized by erythroid hypoplasia often accompanied by growth retardation, congenital craniofacial and limb abnormalities. In addition, Diamond-Blackfan anaemia patients also exhibit a number of behavioural abnormalities. In this study we describe the behavioural effects observed in a new mouse mutant carrying a targeted single amino acid deletion in the ribosomal protein RPS19. This mutant, created by the deletion of arginine 67 in RPS19, exhibits craniofacial, skeletal, and brain abnormalities, accompanied by various neurobehavioural malfunctions. A battery of behavioural tests revealed a moderate cognitive impairment and neuromuscular dysfunction resulting in profound gait abnormalities. This novel Rps19 mutant shows behavioural phenotypes resembling that of the human Diamond-Blackfan anaemia syndrome, thus creating the possibility to use this mutant as a unique murine model for studying the molecular basis of ribosomal protein deficiencies.
- MeSH
- chůze (způsob) fyziologie MeSH
- Diamondova-Blackfanova anemie genetika patologie patofyziologie MeSH
- hydrocefalus patologie MeSH
- metoda rotující tyčky MeSH
- modely nemocí na zvířatech MeSH
- mutace genetika MeSH
- mutantní kmeny myší MeSH
- myši inbrední C57BL MeSH
- nervosvalové spojení patologie patofyziologie MeSH
- nervový systém patologie patofyziologie MeSH
- paměť MeSH
- podmiňování (psychologie) MeSH
- pohyb MeSH
- ribozomální proteiny genetika MeSH
- strach MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ribosomal protein S19 MeSH Prohlížeč
- ribozomální proteiny MeSH
Hereditary cerebellar ataxias are severe diseases for which therapy is currently not sufficiently effective. One of the possible therapeutic approaches could be neurotransplantation. Lurcher mutant mice are a natural model of olivocerebellar degeneration representing a tool to investigate its pathogenesis as well as experimental therapies for hereditary cerebellar ataxias. The effect of intracerebellar transplantation of embryonic cerebellar solid tissue or cell suspension on motor performance in adult Lurcher mutant and healthy wild-type mice was studied. Brain-derived neurotrophic factor level was measured in the graft and adult cerebellar tissue. Gait analysis and rotarod, horizontal wire, and wooden beam tests were carried out 2 or 6 months after the transplantation. Higher level of the brain-derived neurotrophic factor was found in the Lurcher cerebellum than in the embryonic and adult wild-type tissue. A mild improvement of gait parameters was found in graft-treated Lurcher mice. The effect was more marked in cell suspension grafts than in solid transplants and after the longer period than after the short one. Lurcher mice treated with cell suspension and examined 6 months later had a longer hind paw stride (4.11 vs. 3.73 mm, P < 0.05) and higher swing speed for both forepaws (52.46 vs. 32.79 cm/s, P < 0.01) and hind paws (63.46 vs. 43.67 cm/s, P < 0.001) than controls. On the other hand, classical motor tests were not capable of detecting clearly the change in the motor performance. No strong long-lasting negative effect of the transplantation was seen in wild-type mice, suggesting that the treatment has no harmful impact on the healthy cerebellum.
- Klíčová slova
- Ataxia, Cerebellar transplantation, Gait analysis, Lurcher, Olivocerebellar degeneration,
- MeSH
- časové faktory MeSH
- chůze (způsob) MeSH
- metoda rotující tyčky MeSH
- mozeček embryologie metabolismus transplantace MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- multisystémová atrofie patofyziologie terapie MeSH
- myši - mutanty neurologické MeSH
- myši inbrední C57BL MeSH
- myši inbrední CBA MeSH
- myši transgenní MeSH
- pohybová aktivita MeSH
- spinocerebelární degenerace patofyziologie terapie MeSH
- transplantace fetální tkáně metody MeSH
- transplantace mozkové tkáně metody MeSH
- výsledek terapie MeSH
- zelené fluorescenční proteiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- enhanced green fluorescent protein MeSH Prohlížeč
- mozkový neurotrofický faktor MeSH
- zelené fluorescenční proteiny MeSH
To determine whether the exposure to long term enriched environment (EE) would result in a continuous improvement of neurological recovery and ameliorate the loss of brain tissue after traumatic brain injury (TBI) vs. standard housing (SH). Male Sprague-Dawley rats (300-350 g, n=28) underwent lateral fluid percussion brain injury or SHAM operation. One TBI group was held under complex EE for 90 days, the other under SH. Neuromotor and sensorimotor dysfunction and recovery were assessed after injury and at days 7, 15, and 90 via Composite Neuroscore (NS), RotaRod test, and Barnes Circular Maze (BCM). Cortical tissue loss was assessed using serial brain sections. After day 7 EE animals showed similar latencies and errors as SHAM in the BCM. SH animals performed notably worse with differences still significant on day 90 (p<0.001). RotaRod test and NS revealed superior results for EE animals after day 7. The mean cortical volume was significantly higher in EE vs. SH animals (p=0.003). In summary, EE animals after lateral fluid percussion (LFP) brain injury performed significantly better than SH animals after 90 days of recovery. The window of opportunity may be wide and also lends further credibility to the importance of long term interventions in patients suffering from TBI.
- MeSH
- bludiště - učení MeSH
- bydlení zvířat MeSH
- časové faktory MeSH
- chování zvířat * MeSH
- metoda rotující tyčky MeSH
- modely nemocí na zvířatech MeSH
- obnova funkce MeSH
- pohybová aktivita MeSH
- poranění mozku patologie patofyziologie psychologie rehabilitace MeSH
- potkani Sprague-Dawley MeSH
- prostorové chování MeSH
- prostředí kontrolované * MeSH
- regenerace nervu * MeSH
- senzorimotorický kortex patologie patofyziologie MeSH
- velikost orgánu MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The present study examined the hypothesis that the extension of noxious effect of methamphetamine (MA) on maternal behavior and postnatal development on the pups may differ in dependence with time of application. Female rats were injected with MA (5 mg/kg) or saline during first (embryonic day (ED) 1-11) or second (ED 12-22) half of gestation. Our results demonstrated that MA exposure on ED 12-22 led to decreased birth weight and weight gained during lactation period relative to rats treated on ED 1-11. Both sexes treated prenatally with MA on ED 1-11 opened eyes earlier compared to animals treated on ED 12-22. As a matter of sensorimotor development application of MA on ED 1-11 impaired the righting reflex, while MA exposure on ED 12-22 impaired the performance of beam balance test in male rats. There were no differences in maternal behavior. Therefore, it seems that MA exposure in the first half of the gestation impaired the early sensorimotor development that is under control of the brain stem, while the MA exposure in the second half of gestation affected the beam balance performance that is dependent on the function of the cerebellum.
- MeSH
- mateřské chování účinky léků MeSH
- methamfetamin aplikace a dávkování MeSH
- metoda rotující tyčky MeSH
- náhodné rozdělení MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- růst a vývoj účinky léků MeSH
- stimulanty centrálního nervového systému aplikace a dávkování MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- methamfetamin MeSH
- stimulanty centrálního nervového systému MeSH
Mutant mice are commonly used models of hereditary diseases. Nevertheless, these mice have phenotypic traits of the original strain, which could interfere with the manifestation of the mutation of interest. Lurcher mice represent a model of olivocerebellar degeneration, which is caused by the Grid2(Lc) mutation. Lurchers show ataxia and various cognitive and behavioral abnormalities. The most commonly used strains of Lurcher mice are B6CBA and C3H, but there is no information about the role of genetic background on the Grid2(Lc) manifestation. The aim of this work was to compare spatial navigation in the Morris water maze, spontaneous activity in the open field and motor skills on the horizontal wire, slanted ladder and rotarod in B6CBA and C3H Lurcher mutant and wild type mice. The study showed impaired motor skills and water maze performance in both strains of Lurcher mice. Both C3H Lurcher and C3H wild type mice had poorer performances in the water maze task than their B6CBA counterparts. In the open field test, C3H mice showed higher activity and lower thigmotaxis. The study showed that genetic backgrounds can modify manifestations of the Lurcher mutation. In this case, B6CBA Lurcher mice models probably have more validity when studying the behavioral aspects of cerebellar degeneration than C3H Lurcher mice, since they do not combine abnormalities related to the Grid2(Lc) mutation with strain-specific problems.
- Klíčová slova
- Ataxia, Cerebellar degeneration, Genetic background, Lurcher mice, Spatial orientation,
- MeSH
- bludiště - učení * MeSH
- druhová specificita MeSH
- glutamátové receptory genetika MeSH
- metoda rotující tyčky MeSH
- modely nemocí na zvířatech MeSH
- motorické dovednosti * MeSH
- mutace genetika MeSH
- myši - mutanty neurologické psychologie MeSH
- myši inbrední C3H MeSH
- myši MeSH
- nemoci mozečku patologie psychologie MeSH
- olivopontocerebelární atrofie psychologie MeSH
- vnímání prostoru * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- glutamate receptor delta 2 MeSH Prohlížeč
- glutamátové receptory MeSH
Chromatin compaction mediates progenitor to post-mitotic cell transitions and modulates gene expression programs, yet the mechanisms are poorly defined. Snf2h and Snf2l are ATP-dependent chromatin remodelling proteins that assemble, reposition and space nucleosomes, and are robustly expressed in the brain. Here we show that mice conditionally inactivated for Snf2h in neural progenitors have reduced levels of histone H1 and H2A variants that compromise chromatin fluidity and transcriptional programs within the developing cerebellum. Disorganized chromatin limits Purkinje and granule neuron progenitor expansion, resulting in abnormal post-natal foliation, while deregulated transcriptional programs contribute to altered neural maturation, motor dysfunction and death. However, mice survive to young adulthood, in part from Snf2l compensation that restores Engrailed-1 expression. Similarly, Purkinje-specific Snf2h ablation affects chromatin ultrastructure and dendritic arborization, but alters cognitive skills rather than motor control. Our studies reveal that Snf2h controls chromatin organization and histone H1 dynamics for the establishment of gene expression programs underlying cerebellar morphogenesis and neural maturation.
- MeSH
- adenosintrifosfatasy metabolismus MeSH
- analýza rozptylu MeSH
- bromodeoxyuridin MeSH
- chromatinová imunoprecipitace MeSH
- chromozomální proteiny, nehistonové metabolismus MeSH
- fluorescence MeSH
- galaktosidy MeSH
- histony metabolismus MeSH
- homeodoménové proteiny metabolismus MeSH
- hybridizace in situ MeSH
- imunohistochemie MeSH
- indoly MeSH
- koncové značení zlomů DNA in situ MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- metoda rotující tyčky MeSH
- mikročipová analýza MeSH
- morfogeneze genetika fyziologie MeSH
- mozeček embryologie MeSH
- myši transgenní MeSH
- myši MeSH
- nervové kmenové buňky metabolismus fyziologie MeSH
- počítačové zpracování obrazu MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- Purkyňovy buňky metabolismus MeSH
- restrukturace chromatinu fyziologie MeSH
- toloniumchlorid MeSH
- transmisní elektronová mikroskopie MeSH
- vývojová regulace genové exprese genetika fyziologie MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- 5-bromo-4-chloro-3-indolyl beta-galactoside MeSH Prohlížeč
- adenosintrifosfatasy MeSH
- bromodeoxyuridin MeSH
- chromozomální proteiny, nehistonové MeSH
- En1 protein, mouse MeSH Prohlížeč
- galaktosidy MeSH
- histony MeSH
- homeodoménové proteiny MeSH
- indoly MeSH
- Smarca5 protein, mouse MeSH Prohlížeč
- toloniumchlorid MeSH
Perinatal ischemic stroke is a leading cerebrovascular disorder occurring in infants around the time of birth associated with long term comorbidities including motor, cognitive and behavioral deficits. We sought to determine the impact of perinatal induced stroke on locomotion, behavior and motor function in rats. A photothrombotic model of ischemic stroke was used in rat at postnatal day 7. Presently, we induced two lesions of different extents, to assess the consequences of stroke on motor function, locomotion and possible correlations to morphological changes. Behavioral tests sensitive to sensorimotor changes were used; locomotion expressed as distance moved in the open field was monitored and histological changes were also assessed. Outcomes depicted two kinds of lesions of different shapes and sizes, relative to laser illumination. Motor performance of rats submitted to stroke was poor when compared to controls; a difference in motor performance was also noted between rats with small and large lesions. Correlations were observed between: motor performance and exposition time; volume ratio and exposition time; and in the rotarod between motor performance and volume ratio. Outcomes demonstrate that photothrombotic cerebral ischemic stroke induced in early postnatal period and tested in adulthood, indeed influenced functional performance governed by the affected brain regions.
- MeSH
- červeň bengálská * MeSH
- cévní mozková příhoda etiologie patologie patofyziologie psychologie MeSH
- chování zvířat * MeSH
- intrakraniální trombóza etiologie patologie patofyziologie psychologie MeSH
- krysa rodu Rattus MeSH
- lasery * MeSH
- metoda rotující tyčky MeSH
- modely nemocí na zvířatech MeSH
- mozek patologie patofyziologie MeSH
- pohybová aktivita * MeSH
- potkani Wistar MeSH
- psychomotorický výkon * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- červeň bengálská * MeSH