BACKGROUND: Spinocerebellar ataxia 21 (SCA21) is a rare neurological disorder caused by heterozygous variants in TMEM240. A growing, yet still limited number of reports suggested that hyperkinetic movements should be considered a defining component of the disease. CASE SERIES: We describe two newly identified families harboring the recurrent pathogenic TMEM240 p.Pro170Leu variant. Both index patients and the mother of the first proband developed movement disorders, manifesting as myoclonic dystonia and action-induced dystonia without co-occurring ataxia in one case, and pancerebellar syndrome complicated by action-induced dystonia in the other. We reviewed the literature on TMEM240 variants linked to hyperkinetic disorders, comparing our cases to described phenotypes. DISCUSSION: Adding to prior preliminary observations, our series highlights the relevance of hyperkinetic movements as clinically meaningful features of SCA21. TMEM240 mutation should be included in the differential diagnosis of myoclonic dystonia and ataxia-dystonia syndromes.

• Klíčová slova
• Dystonia, Myoclonus, Pro170Leu, SCA21, Spinocerebellar ataxia, TMEM240,
• MeSH
• ataxie MeSH
• dystonické poruchy * MeSH
• dystonie * diagnóza   genetika   MeSH
• hyperkineze MeSH
• lidé MeSH
• membránové proteiny MeSH
• myoklonus * diagnóza   genetika   MeSH
• spinocerebelární degenerace * MeSH
• syndrom MeSH
• vzácné nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Názvy látek
• membránové proteiny MeSH
• TMEM240 protein, human MeSH Prohlížeč

• MeSH
• epilepsie * genetika   MeSH
• hyperkinetická porucha * MeSH
• hyperkineze genetika   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH

Methamphetamine is commonly used psychostimulant in the Czech Republic and is often abused by pregnant women. Methamphetamine may cause abnormalities in placenta and umbilical cord that results in hypoxia and malnutrition. ADHD is a mental disorder with a heterogeneous origin. The number of patients suffering from ADHD is growing. The pathophysiological mechanisms causing ADHD have not yet been clarified. There are very few rat models for ADHD and include genetic models, chemically induced models (ethanol, nicotine, PCBs, 6-hydroxydopamine lesion) or environmentally induced models (anoxia). The aim of the present study was to test prenatal methamphetamine exposure (5 mg/kg) as a potential novel animal model for ADHD. We found that adult male offspring prenatally exposed to methamphetamine presented hyperactivity while exploring novel environments. Together with cognition changes found in our previous studies, these might represent symptoms similar to those seen in ADHD. More experiments are planned to investigate our hypothesis.

• MeSH
• hyperkinetická porucha chemicky indukované   MeSH
• hyperkineze chemicky indukované   MeSH
• methamfetamin škodlivé účinky   MeSH
• potkani Wistar MeSH
• stimulanty centrálního nervového systému škodlivé účinky   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
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH

Calcium/calmodulin-dependent protein kinases (CaMKs) are key mediators of calcium signaling and underpin neuronal health. Although widely studied, the contribution of CaMKs to Mendelian disease is rather enigmatic. Here, we describe an unusual neurodevelopmental phenotype, characterized by milestone delay, intellectual disability, autism, ataxia, and mixed hyperkinetic movement disorder including severe generalized dystonia, in a proband who remained etiologically undiagnosed despite exhaustive testing. We performed trio whole-exome sequencing to identify a de novo essential splice-site variant (c.981+1G>A) in CAMK4, encoding CaMKIV. Through in silico evaluation and cDNA analyses, we demonstrated that c.981+1G>A alters CAMK4 pre-mRNA processing and results in a stable mRNA transcript containing a 77-nt out-of-frame deletion and a premature termination codon within the last exon. The expected protein, p.Lys303Serfs*28, exhibits selective loss of the carboxy-terminal regulatory domain of CaMKIV and bears striking structural resemblance to previously reported synthetic mutants that confer constitutive CaMKIV activity. Biochemical studies in proband-derived cells confirmed an activating effect of c.981+1G>A and indicated that variant-induced excessive CaMKIV signaling is sensitive to pharmacological manipulation. Additionally, we found that variants predicted to cause selective depletion of CaMKIV's regulatory domain are unobserved in diverse catalogs of human variation, thus revealing that c.981+1G>A is a unique molecular event. We propose that our proband's phenotype is explainable by a dominant CAMK4 splice-disrupting mutation that acts through a gain-of-function mechanism. Our findings highlight the importance of CAMK4 in human neurodevelopment, provide a foundation for future clinical research of CAMK4, and suggest the CaMKIV signaling pathway as a potential drug target in neurological disease.

• Klíčová slova
• athetoid cerebral palsy, language impairment, motor deterioration, psychomotor deterioration, torticollis,
• MeSH
• aktivační mutace genetika   MeSH
• cerebelární ataxie genetika   MeSH
• exom MeSH
• exony genetika   MeSH
• fenotyp MeSH
• hyperkineze genetika   MeSH
• lidé MeSH
• mentální retardace genetika   MeSH
• mutace MeSH
• nesmyslný kodon genetika   MeSH
• posunová mutace genetika   MeSH
• proteinkinasa závislá na vápníku a kalmodulinu typ 4 genetika   metabolismus   MeSH
• rodokmen MeSH
• sekvenování exomu MeSH
• sestřih RNA genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CAMK4 protein, human MeSH Prohlížeč
• nesmyslný kodon MeSH
• proteinkinasa závislá na vápníku a kalmodulinu typ 4 MeSH

The programming of cell fate by transcription factors requires precise regulation of their time and level of expression. The LIM-homeodomain transcription factor Islet1 (Isl1) is involved in cell-fate specification of motor neurons, and it may play a similar role in the inner ear. In order to study its role in the regulation of vestibulo-motor development, we investigated a transgenic mouse expressing Isl1 under the Pax2 promoter control (Tg +/- ). The transgenic mice show altered level, time, and place of expression of Isl1 but are viable. However, Tg +/- mice exhibit hyperactivity, including circling behavior, and progressive age-related decline in hearing, which has been reported previously. Here, we describe the molecular and morphological changes in the cerebellum and vestibular system that may cause the hyperactivity of Tg +/- mice. The transgene altered the formation of folia in the cerebellum, the distribution of calretinin labeled unipolar brush cells, and reduced the size of the cerebellum, inferior colliculus, and saccule. Age-related progressive reduction of calbindin expression was detected in Purkinje cells in the transgenic cerebella. The hyperactivity of Tg +/- mice is reduced upon the administration of picrotoxin, a non-competitive channel blocker for the γ-aminobutyric acid (GABA) receptor chloride channels. This suggests that the overexpression of Isl1 significantly affects the functions of GABAergic neurons. We demonstrate that the overexpression of Isl1 affects the development and function of the cerebello-vestibular system, resulting in hyperactivity.

• Klíčová slova
• Age-related deterioration of Purkinje cells, Attention deficit hyperactivity disorder, Calcium homeostasis, Cerebellum, Foliation defects, GABA signaling, Hyperactivity, Islet1 transcription factor, Purkinje cells, Transgenic mouse, Vestibular system,
• MeSH
• hyperkineze metabolismus   patologie   MeSH
• mozeček metabolismus   patologie   MeSH
• myši transgenní MeSH
• myši MeSH
• proteiny s homeodoménou LIM biosyntéza   MeSH
• transkripční faktor PAX2 biosyntéza   MeSH
• transkripční faktory biosyntéza   MeSH
• vestibulární aparát metabolismus   patologie   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
• insulin gene enhancer binding protein Isl-1 MeSH Prohlížeč
• Pax2 protein, mouse MeSH Prohlížeč
• proteiny s homeodoménou LIM MeSH
• transkripční faktor PAX2 MeSH
• transkripční faktory MeSH

OBJECTIVE: We examined the presence of cerebellar symptoms in ADHD and their association with behavioral markers of this disorder. METHOD: Sixty-two children with ADHD and 62 typically developing (TD) children were examined for cerebellar symptoms using the ataxia rating scale and tested using Conners' Continuous Performance Test. RESULTS: Children with ADHD had significantly more cerebellar symptoms compared with the TD children. Cerebellar symptom scores decreased with age in the ADHD group; in the TD group remained stable. In both groups, cerebellar symptoms were associated with parent-rated hyperactive/impulsive symptoms, variability of response time standard error (RT-SE) and increase of RT-SE as the test progresses. More variables were associated with cerebellar symptoms in the ADHD group including omission errors, overall RT-SE and its increase for prolonged interstimulus intervals. CONCLUSION: Our results highlight the importance of research into motor functions in children with ADHD and indicate a role for cerebellar impairment in this disorder.

• Klíčová slova
• Conners’ Continuous Performance Test, attention-deficit/hyperactivity disorder, cerebellum, reaction time variability,
• MeSH
• dítě MeSH
• hyperkinetická porucha patofyziologie   MeSH
• hyperkineze patofyziologie   MeSH
• impulzivní chování fyziologie   MeSH
• lidé MeSH
• mladiství MeSH
• mozeček patofyziologie   MeSH
• nemoci mozku patofyziologie   MeSH
• neuropsychologické testy MeSH
• psychomotorické poruchy patofyziologie   MeSH
• reakční čas fyziologie   MeSH
• senzorimotorický kortex fyziologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The ability of the newly developed bispyridinium compound K203 and its fluorinated analogue KR-22836 to reduce tabun-induced acute neurotoxic signs and symptoms was compared with the currently available reactivator of acetylcholinesterase-obidoxime. Tabun-induced neurotoxicity and the neuroprotective effects of all tested oximes in combination with atropine in rats poisoned with tabun at a sublethal dose (200 μg/kg intramuscularly (i.m.); 80% of LD(50) value) were monitored by a functional observational battery at 24 hr after tabun challenge. The results indicate that all tested oximes combined with atropine were able to survive tabun-poisoned rats 24 hr after tabun challenge while one non-treated tabun-poisoned rat died within 24 hr after tabun poisoning. All tested oximes combined with atropine were able to decrease tabun-induced neurotoxicity in the case of sublethal poisoning but they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. While the ability to reduce tabun-induced acute neurotoxicity of obidoxime and K203 was similar, the neuroprotective efficacy of KR-22836 was slightly higher compared to other tested oximes. Thus, the newly developed fluorinated analogue of K203, called KR-22836, is able to slightly increase the neuroprotective effectiveness of antidotal treatment of acute tabun poisonings compared to K203 and currently available obidoxime.

• MeSH
• akutní nemoc MeSH
• autonomní nervový systém účinky léků   MeSH
• chemické bojové látky otrava   MeSH
• chování zvířat účinky léků   MeSH
• hyperkineze chemicky indukované   prevence a kontrola   MeSH
• krysa rodu Rattus MeSH
• molekulární struktura MeSH
• neuroprotektivní látky aplikace a dávkování   chemie   terapeutické užití   MeSH
• neurotoxické syndromy etiologie   prevence a kontrola   MeSH
• obidoxim chlorid aplikace a dávkování   chemie   terapeutické užití   MeSH
• organofosfáty MeSH
• otrava organofosfáty * MeSH
• oximy aplikace a dávkování   chemie   terapeutické užití   MeSH
• potkani Wistar MeSH
• pyridinové sloučeniny aplikace a dávkování   chemie   terapeutické užití   MeSH
• svalový tonus účinky léků   MeSH
• výsledek terapie 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
• 1-(4-carbamoylpyridinium)-4-(3-fluoro-4-hydroxyiminomethylpyridinium)-but-2-ene MeSH Prohlížeč
• 1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene MeSH Prohlížeč
• chemické bojové látky MeSH
• neuroprotektivní látky MeSH
• obidoxim chlorid MeSH
• organofosfáty MeSH
• oximy MeSH
• pyridinové sloučeniny MeSH
• tabun MeSH Prohlížeč

The aims of the present study were to compare the effect of subchronic administration of MK-801 on performance in the active allothetic place avoidance (AAPA) task and in the working version of Morris water maze (MWM) in Long-Evans and Wistar rats. Animals were trained for four daily sessions either in the AAPA or in the working memory version of the MWM. Wistar rats treated by MK-801 (0.1 mg/kg) showed a cognitive deficit in the AAPA task without a significant hyperlocomotion, whereas they were not impaired in the working memory version of the MWM compared to controls. Long-Evans rats treated by MK-801 (0.1 mg/kg) were not impaired either in the AAPA task or in the MWM task. Higher doses of MK-801 (0.2 and 0.3 mg/kg) produced hyperlocomotion in both strains which corresponded to an inability to solve both spatial tasks. Long-Evans rats were superior in the MWM to the Wistar rats in the groups treated with the low dose of MK-801. In conclusion, intact Wistar rats can efficiently solve both spatial tasks; however, they are more sensitive to MK-801-induced behavioural deficit. This has relevance for modeling of the schizophrenia-related deficits and for screening substances for their therapeutic potential.

• MeSH
• antagonisté excitačních aminokyselin farmakologie   MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• dizocilpinmaleát farmakologie   MeSH
• druhová specificita MeSH
• glutamátové receptory účinky léků   metabolismus   MeSH
• hyperkineze chemicky indukované   patofyziologie   MeSH
• krátkodobá paměť účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• kyselina glutamová metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• mozek účinky léků   fyziologie   MeSH
• nervový přenos účinky léků   fyziologie   MeSH
• orientace účinky léků   fyziologie   MeSH
• poruchy paměti chemicky indukované   patofyziologie   MeSH
• potkani Long-Evans MeSH
• potkani Wistar MeSH
• učení vyhýbat se účinky léků   fyziologie   MeSH
• vnímání prostoru účinky léků   fyziologie   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
• antagonisté excitačních aminokyselin MeSH
• dizocilpinmaleát MeSH
• glutamátové receptory MeSH
• kyselina glutamová MeSH

The objective of this study was to evaluate the adaptability of young Japanese quail chicks to the simulated weightlessness, represented by hypodynamy. Unsexed hatchlings were subjected to hypodynamy on either the first, second or third day of age and reared under these conditions to 21 days of age. During this period, the control quail chicks were housed in a floor box. The effect of hypodynamy on adaptability of chicks was significant (P < 0.001). Approximately 75% of all chicks exposed to hypodynamy were not able to adapt in three experimental groups, although significant differences in adaptability were not found between these groups. Those birds were considered as non-adapted (eliminated from experiment) that manifested hyperactivity, escape attempts, turning 180 degrees in the sling, soaking in the water from the drinker, as well as the total apathy, at least three times per day. This experiment confirmed that some quail chicks are capable of adapting to conditions simulating weightlessness to 21 days of age and that the first 2-weeks after hatching may be a critical period of quail sensitivity to hypodynamy. This finding raises a key issue relevant to rearing quails in simulated weightlessness until the age of sexual maturity.

• MeSH
• časové faktory MeSH
• chování zvířat * MeSH
• Coturnix růst a vývoj   fyziologie   MeSH
• fyzické omezení MeSH
• fyziologická adaptace * MeSH
• hyperkineze etiologie   MeSH
• pohybová aktivita MeSH
• přijímání potravy MeSH
• simulace stavu beztíže škodlivé účinky   mortalita   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

In a previous study of a kindling model using stimulation of the entorhinal cortex we found a redistribution of synaptic vesicles into the close vicinity of the active zone of synapses of Type I (Gray 1959) in the hippocampal gyrus dentatus. In this paper, ultrastructural studies of the same model are being continued using planimetry of the synaptic apparatus. A significant increase of the postsynaptic apparatus, area enlargement by 53%, increase of the perimeter by 28% and shape irregularity are being reported. No changes in shape or in size have been demonstrated in presynaptic structures or in the morphology of presynaptic mitochondria. These findings are discussed in relation to increased functional readiness of the synapses as signs of active reconstruction of the synaptic apparatus.

• MeSH
• elektrofyziologie MeSH
• hipokampus ultrastruktura   MeSH
• hyperkineze patofyziologie   MeSH
• kindling fyziologie   MeSH
• krysa rodu Rattus MeSH
• mitochondrie fyziologie   MeSH
• modely neurologické MeSH
• potkani Wistar MeSH
• synapse fyziologie   MeSH
• synaptické vezikuly fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH