Wyniki wyszukiwania

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Funkcja kalbindyny D - 28k w koordynacji ruchowej

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Barski J. J.

Annals of Warsaw University of Life Sciences - SGGW. Animal Science

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2011

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tom 48

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The role of calbindin D-28k in cerebellum

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Barski J. J.

Acta Neurobiologiae Experimentalis

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2015

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tom 75

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nr Supl.

Calbindin-D28k (calbindin) is a calcium-binding protein expressed in many neuronal populations of the central nervous system. It is generally thought of as calcium buffer, but its cell type-specific physiological roles are unknown. We show that cerebellar Purkinje cell-specific calbindin null mutant mice exhibit a distinct alteration in motor coordination which is primarily due to impaired processing of sensory information. This occurs independent of alterations of synaptic long-term depression but concomitant with selective alteration of synaptically-evoked Ca2+ transients. Whereas AMPA-receptor-mediated transients in Purkinje cell spines and dendrites have larger amplitudes and decay faster, the delayed mGluR-mediated synaptic Ca2+ signal is unaffected. We conclude that calbindin within Purkinje cells, possibly through direct modulation of dendritic Ca2+, is a critical molecular constituent of sensorimotor integration.

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Ultrasound vocalisation (USV) alterations in Purkinje cell specific TSC1 knockout mice

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Wiaderkiewicz J., Barski J. J.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr Suppl.1

Tuberous sclerosis (TSC) is a genetic disorder, characterized by the emergence of multi-system benign tumors. Symptoms related to central nervous system disruptions include seizures, developmental delay and a varying range of behavioral disorders. Behavioral disorders can be identified by analyzing various parameters, many of which can be observed during social interactions where different types of communication come into play. One of the more universal methods of communication in mammals is vocalization, which in mice is realized both in the audible and ultrasonic range. We recorded and analyzed mouse vocalizations during a mousepup isolation test, where newborn mice emit the largest amount of USV’s. A range of sound parameters were analyzed including the rate of vocalization and numerous physical characteristics of sound, as well as single calls which were identified and classified.

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Impact of tuberin (TSC2) gene knockout on locomotor activity, motor coordination and behavioral patterns in mice

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Glowacka M., Barski J. J.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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nr 3

Tuberin (TSC2) is one of the proteins involved in autism spectrum disorders’ pathogenesis (ASD), which together with hamartin (TSC1), is responsible for cellular growth, protein synthesis, and cellular proliferation. The highest concentration of Tuberin has been observed in the cerebellum, particularly in the Purkinje cells. In view of the physiological role of the cerebellum, lack of this protein may impair both locomotor activity and motor coordination. Being one of the factors responsible for ASD, tuberin might also play a role in early behavioral pattern formation. In this work we try to prove these two hypotheses. The study involved three groups of mice: 12 heterozygous TSC (+/-) and 8 mutant TSC (-/-) mice were compared with a control group of 7 wild-type C57BL/6 mice. All the mice were introduced into the study at the age of 6 weeks. Each mice underwent the following standardized tests: the RotaRod test, the Elevated Runway test, the Open Field test. All the tests were performed three times- at the age of 6, 12 and 28 weeks. Both the RotaRod and the Elevated runway tests revealed significantly impaired motor coordination skills in the mutant mice compared with both the control and the heterozygous group. Furthermore, the TSC (-/-) mice exhibited a noticeably lower level of explorative activity and higher levels of fear.

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Socialization assessment of TSC1 knockout mice

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Wiaderkiewicz J., Barski J. J.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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nr 3

Tuberous sclerosis (TSC) is a genetic disorder, linked to the TSC1 gene and characterized by the emergence of multi-system benign tumors. Symptoms related to central nervous system disruptions include seizures, developmental delay and a varying range of behavioral disorders. These disorders can be identified by analyzing various parameters, many of which can be observed during social interactions. Cre recombinase mediated TSC1 gene knockout mice were constructed and analyzed for sociability and preference for social novelty. The test was performed in a standard threechamber sociability cage and results were obtained and analyzed using automated tracking software Ethovision XT from Noldus.

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Insights into the physiology of neuronal calbindin D28k from calbindin nullmutant and transgenic mice

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Barski J. J., Meyer M.

Acta Neurobiologiae Experimentalis

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1999

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tom 59

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nr 3

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Complex social behavior and brain morphology of Labroides dimidiatus

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Chojnacka D., Barski J. J.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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nr 3

Labroides dimidiatus (Labridae) is a model fish in research concerning cleaner fish mutualism. Recent studies shows that cleaners are capable to build up complicated relationships (Bshary and Würth 2001). Cleaners recognize clients individually, they remember past interactions with clients, they may cooperate, reconcile, manipulate, cheat, produce signals out of context, and use predatory clients as social tools against aggressive clients (Bshary 2011). The apparent complexity of cleaner fish behavior makes them a particularly interesting object of comparative analysis of morphology and cytoarchitecture of brain and brain centers in telencephalon, optic tectum and cerebellum, parts of the brain potentially involved in cognitive functions related to behaviors in complex social environment (Demski and Beaver 2001). A cytoarchitectonic study shows in the telencephalic regions responsible for the control of the processes related to visual information, a complex cortical structure; a columnar arrangement of cells in the region responsible for the integration of multimodal information; and duplication of nuclei in vetral part of the telencephalon. Nuclei connected with olfactory information were poorly developed. Proportions, complexity and size of the optic tectum layers, tori semicircularis, tori longitudinalis, and the cerebellum proved diversified importance of visual organs, small role of hearing and lateral line, and complex and well developed skills associated with the spatial mapping and complex locomotion.

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Comparative analysis of brain cytoarchitecture of labroid fishes with different degree of cognitive abilities

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Chojnacka D., Barski J. J.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr Suppl.1

Labroides dimidiatus (Labridae) is a model fish in research concerning cleaner fish mutualism. Recent studies shows that cleaners possess the ability to establish complicated relationships (Bshary and Würth 2001). This well-developed network is one of the most complex interspecies communication systems known in fishes and require complex cognitive abilities (Marshall et al. 2003). It makes the cleaners particularly interesting object of comparative analysis of morphology and cytoarchitecture of brain and brain centers in telencephalon, optic tectum and cerebellum, parts of the brain potentially involved in cognitive functions related to behaviors in complex social system (Demski and Beaver 2001). Similar conclusion were drawn in primates, Carniforous and bats, where strong correlations between development of neocortex and size of social group (as measurement of the complexity of social behavior) were found (Dunbar 1992, Joffe and Dunbar 1997, Bshary and Würth 2001). According to the basic theoretical assumption, centers located in the telencephalon, optic tectum and cerebellum involved in skills associated with complex social behavior, learning and memory, differ qualitatively and quantitatively between cleaners and species with less complicated behavior.

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Impact of tuberin (TSC2) gene knockout on ultrasonic vocalizations in mouse pups

63%

Glowacka M., Barski J. J.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr Suppl.1

Tuberin (TSC2) is one of the proteins involved in autism spectrum disorders’ pathogenesis. Together with hamartin (TSC1), tuberin is responsible for protein synthesis, cellular growth and proliferation. Lack of these proteins causes tumors, hamartomas, observed in the central nervous system of affected patients. Additionally 25–60% of patients with tuberous sclerosis complex develop autism spectrum disorders. The highest concentration of tuberin has been noted in the cerebellum, particularly in the Purkinje cells. Purkinje cells may participate in the process of emission of ultrasounds (ultrasonic vocalization – USV), which can be analyzed as parameter of early stages of intercommunication development. Expression of tuberin in the cerebellar Purkinje cells was switched-of by means of the Cre/loxP transgenic technolgy. The study involved two groups of mice: homozygous for the mutation TSC2Cre-/- and control group TSC2Cre+/+. All the mice were introduced into the study at the age of 2 days and the USV was recorded every two days until the age of 14 days. To record and analyze the ultrasounds we used the Ultrasound Recording Device and software by Avisoft Bioacustics. Preliminary data suggest subtle alterations of USV, but more experiment is needed to support first observations.

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Selected behavioral and motor parameters in Bcl-2 knockout mice

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Slugocka A., Barski J. J.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr Suppl.1

Bcl-2 knockout mice doesn’t produce Bcl-2 protein – one of the major protein factors regulating apoptotic processes involved in development of the nervous system. Bcl-2 deficiency result in increased cell death of motoneurons, sensory and sympathetic neurons (Michaelidis et al. 1996). Only very sparse data on impact of this mutation on motor activity and behavior are available. In the present study we examined the exploratory activity of knockout mice in the open field task, and checked motor related behaviors by means of RotaRod, elevated runway test, strength grip test, and balance rod test. Preliminary data suggest lack of prominent alteration of analyzed parameters, but more experiments are planned to look for possible more subtle changes.

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Fish and animal models in biomedical research

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Chojnacka D., Barski J. J.

Acta Neurobiologiae Experimentalis

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2019

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tom 79

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nr Suppl.1

INTRODUCTION: In biomedical research, there is a constant lookout for animal models that can help in the search for new drugs and therapies. The most commonly used are laboratory mice and rats, but their use is under pressure of the need to reduce used animals. Many experiments can be performed on simpler vertebrates such as fish, but even here the choice of species is crucial. METHOD(S): I used a comparison between the same types of experiments conducted on fish and other groups of animals based on published data. RESULTS: Regarding complex cognitive mechanisms, there is experimental evidence for diverse processes such as cognitive maps, transitive inference, complex social learning rules, referential gestures, generalization, or mirror recognition in fish. Recent research on vertebrate brains has also identified amazingly conserved structures with respect to a so-called social decision-making network, which consists of the ‘social behaviour network’ and the ‘basal forebrain reward system’. CONCLUSIONS: Given these similarities, fish seem to offer vast opportunities for testing general principles concerning social behavior and underlying cognitive mechanisms and processes. There is also a need to create special equipment to study more sophisticated behavioral tasks in fish that could be compared with that of rats and mice. Additionally, behavioral tests combined with the analysis of the brain structure will allow us to understand the differences in processing information concerning social and environmental behaviors.

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Ultrasonic vocalization (USV) in calbindin D-28k mutant mice

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Grabowska M., Slugocka A., Barski J. J.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr Suppl.1

Mice similarly to some other rodent species communicate with specialized sounds in the ultrasonic range called ultrasonic vocalizations (USV). Evaluation of this behavioral activity enables estimation of the social interactions in animal models of diseases involving psychiatric manifestations related to the social environment like autistic spectrum disorders (ASD). Because of the growing evidence for involvement of cerebellum in ethiology of ASD, we decided to change physiological properties of Purkinje cells and look for signs of alterations in USV activity of newborns. In our experiments we switched off expression of the major protein calcium buffer (calbindin D-28k) in these neurons by means of the Cre/loxP technology. It is known from previous reports (1), that the lack of calbindin D-28k in cerebellar cortex results in motor coordination deficits due to disturbed processing of calcium signaling in Purkinje cells. Because coordination of the vocal apparatus depends on the cerebellar input we were curious if altered Purkinje cells function results in altered USV calling.

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Impact of ketogenic diet on gait in Purkinje cell specific transgenic mouse model of tuberous sclerosis complex

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Slugocka A., Grabowska M., Barski J. J.

Acta Neurobiologiae Experimentalis

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2019

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tom 79

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nr Suppl.1

INTRODUCTION: The ketogenic diet is a high fat low carbohydrate diet, wherein the majority of caloric needs is covered by fats with very low carbohydrate intake. The diet is widely used not only by athletes and patients suffering from obesity or diabetes, but also by patients with intractable epilepsy. The high fat, low carbohydrate diet is extensively studied within the fields of numerous diseases including cancer and neurological disorders. METHOD(S): In present study, we used Purkinje cell (PCs) specific knockout mice lacking hamartin (tsc1), a key protein involved in mTORC1 pathway. Deletion of Tsc1 gene in PCs results in a loss of these cells and gait impairments. We implemented a ketogenic rodent chow to reveal its potential influence on prevention of loss of PCs in the cerebellum. We assessed the effects of treatment with the ketogenic diet on the quality of mice gait. The gait was analysed in the CatWalk system from Noldus. Obtained data were compared among groups: control animals, with tsc1 in PCs, fed with standard rodent diet, animals with tsc1 but fed with ketogenic chow and knockout mice, fed respectively with two types of abovementioned diets. RESULTS: Our results revealed that, as expected, animals without hamartin in PCs present severe gait disturbances. Supplementation of the ketogenic diet has no effect on gait disturbances caused by deletion of tsc1 in PCs. CONCLUSIONS: Additionally, statistical analysis of data obtained from animals without gene deletion didn’t bring any proof of differences in gait parameters between groups fed with two different chows.

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Ultrasonic vocalization (USV) patterns in Eker rat newborns

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Slugocka A., Chojnacka G., Grabowska M., Barski J. J.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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nr 3

Tuberous sclerosis complex (TSC) is one of the most frequent neurocutaneous disorders mostly present in pediatric patients. In TSC development we can observe neuropsychiatric signs with symptoms of epilepsy, mental retardation, and autism. Molecular mechanism of this disease involves two genes TSC1 and TSC2. Expression of both of them results in two proteins tuberin and hamartin negatively regulating mTOR signaling pathway. Mutations in TSC1 or TSC2 disturb their inhibitory function, what impairs the proliferation machinery downstream of mTOR. It results in growth of tumors (tubers) in many organs including the brain structure. Eker rat is a strain, that carries a spontaneously occurring germline mutation in the TSC2 gene. By the age of 1 year all TSC2Ek/- animals develop renal epithelial tumors. Tumors also appear in the brain tissue and make the strain a suitable model of autism spectrum disorders (ASD). One of the symptoms specific for autistic-like behaviors is the impaired communication between mother and child. Many rodent species including mouse and rat emit at the ultrasonic range (USV) sounds – a vocal communication between mother and offspring. This phenomenon is a good indicator of social interactions and alterations of the USV can be analyzed by means of specialized recording systems. In our study we attempted to check if there are any differences between TSC2Ek/- genotype newborns and wild type ones in patterns of USV using the standard isolation test. We analyzed sonographic structure of calls, number of calls per minute, duration of single call, etc.

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Mouse specific expression of the novel splice variant of Pcp2/L7

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Barski J. J., Przybyla M., Nowacka-Chmielewska M.

Acta Neurobiologiae Experimentalis

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2017

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tom 77

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nr Suppl.1

INTRODUCTION: Pcp2/L7 is a member of the GoLoco protein family with a very cell‑specific expression in cerebellar Purkinje cells and retinal bipolar neurons. Its precise functional role remains still unclear. Sparse studies indicated its possible role as a guanine nucleotide dissociation inhibitor or guanine nucleotide exchange factor. Studies on genomic structure of pcp2 gene revealed some alternative splice variants expressed in Purkinje cells and retinal bipolar neurons. AIM(S): Here we attempted to shed some light on the conservation of a novel pcp2 splice variant in closely related laboratory rodents: mouse, rat and hamster. METHOD(S): PCR: Both splice variants were amplified with the primers L7sense and L7anti, which yielded two reaction products of 371 and 312 bp. The novel splice variant including exon 3B was detected using the primers L7sense (as above) and L73Aanti, for a product size of 274 bp. Quantitative real‑time PCR (qPCR) analysis: To validate the results obtained by RT-PCR, we conducted an additional qPCR experiment to investigate the expression of Pcp2 transcripts with greater accuracy. The region of interest was amplified from cDNA resulting in a product size of 90 bp.Relative gene expression levels were calculated with the 2‑ΔΔCt method. RESULTS:In our approach we were able to confirm expression of the novel longer transcript in mouse, however PCR amplification on cDNA from rat and hamster did not reveal the long splice variant with additional exon 3B*. CONCLUSIONS: Obtained data indicate, that the novel splicing variant of pcp2 is mouse‑specific and is expressed only in Purkinje cells and retinal bipolar neurons in this species. In course of the evolution it appeared probably in that species as result of a spontaneous mutation. Herewith we suggest a very specific and not known yet function of pcp2 in the mouse eye and/or Purkinje cells. FINANCIAL SUPPORT: Research supported by the Ministry of Science and Higher Education core grant #KNW-2-011/D/4/N.

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Changes in the repetitive stereotyped characteristic of calcium binding proteins (CaBPs) knockout mice in the autistic-like behavior

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Grabowska M., Slugocka A., Barski J. J.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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nr 3

Autism is a multifactorial disorder that involves impairments in social interactions and communication, as well as restricted and repetitive behaviors. Recent whole-genome exon sequencing studies of ASD (autism spectrum disorders) samples estimate that as many as 100 to 1 000 genes may be involved. So different candidate genes have been tested in mouse models by knocking them out. Calbindin D-28k (CB) and parvalbumin (PV) are cytosolic calcium-binding proteins expressed in many neurons without general preference for functionally and morphologically defined subpopulations. Deletion of CB and/or PV alters intracellular calcium signaling, and physiological properties of affected neurons. General knockouts for both proteins display a distinct and permanent motor impairment which is revealed only when adaptation of movement to novel environmental conditions is required. In order to determine whether the absence of CB and PV influences locomotor properties and behavior we compared mouse lacking CB, PV, or both with wild type controls. The mice were compared in the open field task and in the light-dark compartment tests to measure activity, exploratory behavior, and restricted and repetitive behaviors (TruScan, Coulbourn, USA). Relative to wild-type mice, the transgenic mice exhibited much more stereotypic movements in the open field test. Multiple mouse behavioral effects suggest that the CB and PV genes may play a role in modulating behaviors relevant to psychiatric disorders.

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Two different classes of 22-kHz ultrasonic vocalizations during sexual interactions, correlation with rat behavioral state

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Bialy M., Podobinska M., Barski J. J., Bogacki-Rychlik W., Sulkowska-Sajdel E.

Acta Neurobiologiae Experimentalis

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2017

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tom 77

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nr Suppl.1

INTRODUCTION: Low frequency ultrasonic vocalizations, commonly referred as 22‑kHz, occur in different situations including both aversive as well as positive emotional states in rats. Our previous research suggests that following ejaculation, long, lasting low frequency vocalizations reflect a positive emotional state – relaxation after high arousal state. It has been found that there is another type of 22-kHz vocalizations, which occurs during sexual interactions – at the time of firstseparated‑noncontact test. AIM(S): The aim of our study was to investigate the spectral analysis of low frequency ultrasonic vocalizations when male is prevented from a direct contact with estrous female and compare such calls to postejaculatory vocalizations. METHOD(S): The subjects were Long–Evans males (N=9) and female (N=9) rats 4.5 months old at the start of the experiment. The clear Plexiglas test chamber (50×25×30 cm) was used for copulatory and barrier noncontact (NC) tests. For NC tests, the chamber was bisected. Behaviors were recorded using Noldus Ethovision system simultaneously, on the same computer, with ultrasounds recording using Metris Sonotract system and analyzed manually. RESULTS: We found that about half of males prevented from a direct contact with an estrous female vocalized at frequency below 30-kHz. These vocalizations usually initiated with short signal at higher 45-kHz frequency and then transited to lower, below 30-kHz frequency. Usually these vocalizations coexist with sniffing of a hole or exploration activities – rearing or sniffing cage. The high activity state observed in separated males during low frequency vocalization is in contrast to male immobility observed during postejaculatory period when male emit extremely flat 22-kHz ultrasonic vocalizations. CONCLUSIONS: A pattern of low frequency vocalizations in rats during frustration differs significantly from that observed during relaxation state after ejaculation and correlates to the different type of behavioral activity. FINANCIAL SUPPORT: This work was supported by the Medical University of Warsaw (grant 1MA/N/170 and mini Grant for Wiktor Bogacki-Rychlik.

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The influence of various compositions of the ketogenic diet on the behavior of selected mouse strains

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Grajoszek A., Jablonska K., Jablonska K., Grabowski M., Barski J. J.

Acta Neurobiologiae Experimentalis

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2019

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tom 79

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nr Suppl.1

INTRODUCTION: High fat diets are characterized by a high fat content with an adequate proportion of proteins and carbohydrates. For a long time, the ketogenic diet has been used in the treatment of epilepsy; however, its neuroprotective properties indicate its putative and broader application in the treatment of neurodegenerative diseases and neurodevelopmental disorders. AIM(S): The present study is focused on the selection of a proper animal model in the preclinical studies on ketogenic therapeutic potential. METHOD(S): The study involved 160 male mice from 129/SV and C57 BL/6 strains at the age of 9 weeks. The animals were divided into 4 groups. The control groups have been fed with a standard diet and the experimental groups were fed with three different types of a high fat diet: (A) a diet imitating a classic ketogenic diet composed mainly of saturated fats of animal origin, where the ratio of fat to carbohydrates and proteins is 4:1, (B) a diet imitating a modified ketogenic diet with a high content of unsaturated fat of vegetable origin, where the ratio of fat to carbohydrates and proteins is 4:1, or (C) a diet imitating ketogenic diet, containing fats of animal origin where the ratio of fats to carbohydrates and proteins is 6:1. On the 100th day of the experiment, the animals of all groups were subjected to motor and behavioral tests, including: an open field test, elevated plus maze, test on a raised treadmill, and a Grip Test. After testing, the animals were euthanized to collect material for further analysis. CONCLUSIONS: The collected samples will be used to determine the level of expression of selected genes and the level of neurogenesis in the hippocampal dentate gyrus.

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Content and composition of proteins obtained from short-time-predegenerated distal stumps of rat sciatic nerves

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Gorka D., Larysz-Brysz M., Lewin-Kowalik J., Krause M., Barski J. J.

Applied Biology Communications. Lublin Scientific Center

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1994

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tom 04

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nr 3-4

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Ketogenic diet and sexual motivation in male rats

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Bogacki-Rychlik W., Bialy M., Grajoszek A., Przybyla M., Slugocka A., Barski J. J.

Acta Neurobiologiae Experimentalis

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2019

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tom 79

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nr Suppl.1

INTRODUCTION: The ketogenic diet (KD) is a very‑low‑carbohydrate, high‑fat and adequate protein nutritional approach that induces metabolic shift to the use of ketone bodies instead of glucose as a main energy source. For decades, the KD has been employed to manage drug-resistant epilepsy, but recently it is increasingly considered as an alternative or add-on therapy in many other disorders. The positive effect of the KD on social behavior has been recently reported in rodent models of autism spectrum disorder (ASD) and wild type early adult male rats. AIM(S): Given, however, the influence of ketone bodies on many humoral parameters including testosterone, we decided to look closer at the sexual interactions of male rats subjected to the KD. METHOD(S): In our study, we examined behavior of males in response to female presence with concomitant analysis of ultrasonic vocalizations (USV) during sexual interactions. RESULTS: Percent of males starting to copulation significantly decreased during the second sexual session, which suggests lower sexual motivation in male rats on the KD. FINANCIAL SUPPORT: Funding: Ministry of Science and Higher Education, grant number KNW‑1‑053/N/8/I.

Ograniczanie wyników

Funkcja kalbindyny D - 28k w koordynacji ruchowej

The role of calbindin D-28k in cerebellum

Ultrasound vocalisation (USV) alterations in Purkinje cell specific TSC1 knockout mice

Impact of tuberin (TSC2) gene knockout on locomotor activity, motor coordination and behavioral patterns in mice

Socialization assessment of TSC1 knockout mice

Insights into the physiology of neuronal calbindin D28k from calbindin nullmutant and transgenic mice

Complex social behavior and brain morphology of Labroides dimidiatus

Comparative analysis of brain cytoarchitecture of labroid fishes with different degree of cognitive abilities

Impact of tuberin (TSC2) gene knockout on ultrasonic vocalizations in mouse pups

Selected behavioral and motor parameters in Bcl-2 knockout mice

Fish and animal models in biomedical research

Ultrasonic vocalization (USV) in calbindin D-28k mutant mice

Impact of ketogenic diet on gait in Purkinje cell specific transgenic mouse model of tuberous sclerosis complex

Ultrasonic vocalization (USV) patterns in Eker rat newborns

Mouse specific expression of the novel splice variant of Pcp2/L7

Changes in the repetitive stereotyped characteristic of calcium binding proteins (CaBPs) knockout mice in the autistic-like behavior

Two different classes of 22-kHz ultrasonic vocalizations during sexual interactions, correlation with rat behavioral state

The influence of various compositions of the ketogenic diet on the behavior of selected mouse strains

Content and composition of proteins obtained from short-time-predegenerated distal stumps of rat sciatic nerves

Ketogenic diet and sexual motivation in male rats