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1.
J Neurol ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898269

RESUMO

BACKGROUND: Leg stereotypy syndrome (LSS) is a very common, yet underrecognized condition. The pathophysiology of the condition is not well understood. OBJECTIVE: To evaluate and describe the visual kinematic characteristics of the repetitive leg movements in individuals with LSS. METHODS: In this study, we identified and videotaped individuals diagnosed with LSS at the Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas between 2000 and 2023. Only patients with LSS and without any co-morbidities were included in the study. Their medical records were carefully reviewed, and the demographic and clinical data were entered into a database. Video recordings of the repetitive leg movements were then analyzed using TremAn software. RESULTS: We identified 14 individuals with LSS who were videotaped at our center. The videos of the 5 cases were too brief and therefore not suitable for TremAn quantitative analysis. The remaining 9 individuals exhibited regular rhythmic oscillations of the legs. Among these, two individuals displayed rhythmic movements only in video segments where their legs were in crossed positions. The other 7 individuals had regular rhythmic oscillations, always with the toes resting on the floor with the heels raised. Frequency analysis showed values between 4.5 and 6.5 Hz, fairly consistent with a variance below 0.5 Hz in individual cases. The oscillation frequency changed from 5.7 Hz to 2.7 Hz while standing. CONCLUSION: In this study, 6 of 9 individuals with LSS showed 4.5-6.5 Hz regular rhythmic leg movements. Studies involving a larger LSS population with additional electrophysiological evaluations are needed to obtain further insights into this common movement disorder.

2.
Innov Clin Neurosci ; 21(4-6): 11-13, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38938532

RESUMO

Stimulants are the first-line pharmacological treatment for attention deficit hyperactivity disorder (ADHD). We present the unique case of a patient who developed a chewing compulsion when taking mixed amphetamine salts (MAS). A 32-year-old female patient with a past medical history of gastroesophageal reflux disease (GERD), gastroparesis, and migraines was seen for initial psychiatric assessment due to concerns for irritability. She was diagnosed with post-traumatic stress disorder (PTSD); generalized anxiety disorder; ADHD, inattentive type; and unspecified bipolar disorder. Lamotrigine was started and titrated to 25mg twice per day, with improved mood stability. MAS immediate-release (IR) was started at 2.5mg and titrated to 5mg daily for ADHD. She then experienced an uncontrollable urge to chew, finding relief when chewing on a child's teething necklace, which provided satisfaction and a reduction in anxiety. She denied jaw tightness or teeth grinding. The dose of MAS IR was reduced to 2.5mg daily with improvement in symptoms and later increased again to 5mg daily, which she was then able to tolerate. Stereotyped biting behaviors have been observed in rats with the use of amphetamines, and the onset of compulsive behavior has emerged in children with the use of dextroamphetamine. However, this is the first known case of compulsive chewing or biting movements reported in humans with MAS use. This case highlights the need to assess patients for adverse events, such as compulsive biting and chewing movements or other oral facial stereotypies, after commencement of stimulants, including MAS.

3.
Behav Modif ; : 1454455241255085, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819977

RESUMO

Complex motor stereotypies are rhythmic, repetitive, fixed, and non-goal directed movements (e.g., bilateral flapping/waving movements of the hands/arms). Movements typically begin in early childhood and can occur in otherwise normally developing ("primary") or autistic ("secondary") children. Stereotypies persist, occur multiple times a day, have prolonged durations, can be socially stigmatizing, and may lead to bullying and isolation. Prior behavioral treatment studies have focused on older children (ages 6-12) and report modest reductions in stereotypy (i.e., between 14% and 33%). The current study involves the functional assessment and treatment of five children with Primary Complex Motor Stereotypy using a modified awareness training procedure, differential reinforcement of other behavior, and schedule thinning in a nonconcurrent multiple baseline design. Results suggest a 99% reduction of motor stereotypy from baseline across all participants.

4.
J Appl Anim Welf Sci ; : 1-16, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38577826

RESUMO

Environmental enrichment may reduce stereotypies in fur-farmed mink. North American mink standards require manipulable enrichment objects within cages. However, mink can rapidly destroy objects inhibiting continuous enrichment presence, which may have negative welfare impacts. This experimental study determined the effects of removing simple cage manipulable enrichments (plastic chains and dumbbells), either short-term or longer-term, on the behavioral expression of welfare in fur-farmed mink. Locomotor stereotypies, normal activity, sub-types of inactivity related to boredom, and tail fur-chewing were recorded across four treatment groups with either (1) no enrichment, (2) continuous enrichment, (3) short (temporary), or (4) long-term enrichment removal. Contrary to predictions, locomotor stereotypies, and scrabbling were not reduced by the enrichments, nor affected by the enrichment removal. Observations at the beginning of the trial showed the non-enriched mink spent the least amount of time lying with their eyes open (i.e., the least bored). The lack of enrichment may have increased fur-chewing on the tail, but larger sample sizes would be needed for statistical confirmation. This research contributes to the literature on evaluating simple, practical enrichments for improving fur-farmed mink welfare.

5.
Poult Sci ; 103(6): 103692, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38598915

RESUMO

Feather sucking, or feather licking, has been reported anecdotally by employees in the Australian meat chicken breeder industry, but scarcely in the scientific literature. Consequently, the causes and implications of this behavior in meat chicken breeding chickens is relatively unknown. We surveyed 17 industry experts to generate hypotheses about feather sucking behavior. We aimed to understand the frequency and when it occurs, and attempted to understand what may cause an "outbreak". The recruitment of participants was intentionally biased towards Australian perspectives; only 5 of the 17 participants were international. All participants, except 1, had seen feather sucking/licking behavior (94.1%) and most participants (80%) suggested that the behavior was most frequently observed during rearing. Participants presented varying concerns about this behavior, ranging from the perspective that it was "normal" and had no impact on welfare, to concerns about mating injuries due to damaged feathers, increased risk of feather pecking and cannibalism, and psychological stress indicated by expression of repetitive (seemingly) functionless behavior. "Feather licking," "feather sucking," "feather eating," and "feather pecking" were terms used interchangeably, leading to confusion by participants about the cause and implications of the target behavior. The most common factors reported as the cause were boredom (52.9%), nutritional deficiencies (47.1%), and feed restriction (41.2%) and more than 80% of respondents agreed that stress contributes to feather sucking. The outputs from this study reflect only a small, but expert, number of opinions on feather sucking/licking behaviors in the Australian meat chicken breeder industry. A systematic understanding of this behavior is needed to provide insight into causation and the implications for welfare.


Assuntos
Criação de Animais Domésticos , Galinhas , Plumas , Animais , Galinhas/fisiologia , Criação de Animais Domésticos/métodos , Austrália , Bem-Estar do Animal , Comportamento Animal/fisiologia , Feminino
6.
Behav Genet ; 54(3): 290-301, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38536593

RESUMO

Head grooming in Drosophila consists of repeated sweeps of the legs across the head, comprising regular cycles. We used the GAL4-UAS system to study the effects of overexpressing shibirets1 and of Adar knockdown via RNA interference, on the period of head-grooming cycles in Drosophila. Overexpressing shibirets1 interferes with synaptic vesicle recycling and thus with cell communication, while Adar knockdown reduces RNA editing of neuronal transcripts for a large number of genes. All transgenic flies and their controls were tested at 22° to avoid temperature effects; in wild type, cycle frequency varied with temperature with a Q10 of 1.3. Two experiments were performed with transgenic shibirets1: (1) each fly was heat-shocked for 10 min at 30° immediately before testing at 22° and (2) flies were not heat shocked. In both experiments, cycle period was increased when shibirets1 was overexpressed in all neurons, but was not increased when shibirets1 was overexpressed in motoneurons alone. We hypothesize that grooming cycles in flies overexpressing shibirets1 are lengthened because of synaptic impairment in neural circuits that control head-grooming cycles. In flies with constitutive, pan-neuronal Adar knockdown, cycle period was more variable within individuals, but mean cycle period was not significantly altered. We conclude that RNA editing is essential for the maintenance of within-individual stereotypy of head-grooming cycles.


Assuntos
Proteínas de Drosophila , Drosophila , Humanos , Animais , Proteínas de Drosophila/metabolismo , Dinaminas/genética , Dinaminas/metabolismo , Asseio Animal , Neurônios/metabolismo , Drosophila melanogaster/genética
7.
Adv Neurobiol ; 36: 677-692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468058

RESUMO

Depression is currently one of the most complicated public health problems with the rising number of patients, increasing partly due to pandemics, but also due to increased existential insecurities and complicated aetiology of disease. Besides the tsunami of mental health issues, there are limitations imposed by ambiguous clinical rules of assessment of the symptoms and obsolete and inefficient standard therapy approaches. Here we are summarizing the neuroimaging results pointing out the actual complexity of the disease and novel attempts to detect depression that are evidence-based, mostly related to electrophysiology. It is repeatedly shown that the complexity of resting-state EEG recorded in patients suffering from depression is increased compared to healthy controls. We are discussing here how that can be interpreted and what we can learn about future effective therapies. Also, there is evidence that novel options of treatment, like different modalities of electromagnetic stimulation, are successful just because they are capable of decreasing that aberrated complexity. And complexity measures extracted from electrophysiological signals of depression patients can serve as excellent features for further machine learning models in order to automatize detection. In addition, after initial detection and even selection of responders for further therapy route, it is possible to monitor the therapeutic flow for one person, which leads us to possible tailored treatment for patients suffering from depression.


Assuntos
Depressão , Fractais , Humanos , Eletroencefalografia/métodos , Neuroimagem
8.
Behav Modif ; 48(4): 420-448, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38390868

RESUMO

Competing stimulus assessments (CSA) are effective tools for identifying stimuli that compete with automatically reinforced behavior. However, Jennett et al. suggests there are cases for which non-contingent access to competing stimuli are insufficient at decreasing target responding and additional treatment components may be necessary. The purpose of the current study was to examine procedural variations (i.e., rotating competing items and prompted engagement) when presenting competing stimuli on increasing functional engagement and decreasing stereotypy. Following a functional analysis, a CSA was conducted to identify competing stimuli for four individuals with autism. Items identified were then used with two procedural variations. Levels of stereotypy, functional engagement, and item contact were measured. Results showed that for two participants both treatments were effective, while for the other two participants prompting functional engagement was more effective. Prompting functional engagement is likely a productive strategy for enhancing engagement with competing stimuli for automatically reinforced problem behavior as it may result in functional engagement becoming reinforcing in and of itself.


Assuntos
Transtorno Autístico , Terapia Comportamental , Reforço Psicológico , Comportamento Estereotipado , Humanos , Masculino , Terapia Comportamental/métodos , Criança , Transtorno Autístico/terapia , Transtorno Autístico/psicologia , Feminino , Transtorno do Espectro Autista/terapia , Adolescente , Pré-Escolar , Transtorno de Movimento Estereotipado/terapia
9.
J Appl Behav Anal ; 57(2): 444-454, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38379177

RESUMO

Response interruption and redirection (RIRD) is a common treatment for automatically reinforced vocal stereotypy; it involves the contingent presentation of task instructions. Tasks that are included in RIRD are typically selected based on caregiver report, which may affect the efficacy of RIRD. The purpose of the current study was to evaluate the role of task preference in the efficacy of RIRD for four participants who engaged in vocal stereotypy. We conducted task-preference assessments and selected tasks of varying preferences to include in RIRD. For three out of four participants, the results showed that RIRD with higher preference tasks was not effective at reducing vocal stereotypy, whereas RIRD with lower preference tasks was effective for all participants.


Assuntos
Transtorno de Movimento Estereotipado , Voz , Humanos , Terapia Comportamental/métodos , Comportamento Estereotipado/fisiologia , Transtorno de Movimento Estereotipado/terapia
10.
Brain Behav ; 14(1): e3375, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38376023

RESUMO

BACKGROUND: Our previous study showed that functional seizures (FS) are consistent in the same patient during a single video EEG monitoring (VEEG). This study aimed to check whether FS remains consistent across VEEG sessions even after several years. METHODS: The study evaluated the consistency of FS across different VEEG sessions using five criteria: FS type, the main anatomical region involved (specifically, the body part most affected during the seizure), other involved anatomical regions, frequency of movements, and duration of FS. Consistency levels were categorized as low (one consistent axis), moderate (two consistent axes), and high (three or more consistent axes). RESULTS: Fourteen patients were included in the final analysis. The mean time between monitoring was 3.8 ± 2.5 years (0.5-8 year). In 13 of 14 patients, the first and second monitoring events were classified into the same FS category. There was consistency in the main anatomical region involved in 9 out of 12 patients with motor FS. In 9 out of 12 patients with motor FS, the other anatomical regions involved were consistent in both sessions. The mean duration of the FS between sessions was inconsistent in most of the patients. Ten patients were classified with high consistency, one patient with moderate consistency, two patients with low consistency, and in one patient, the events were classified as inconsistent. CONCLUSIONS: Our results show that FS tends to remain consistent in a single patient even after several years, and there is probably no correlation between the degree of consistency and the time between VEEG sessions. These findings have implications for supporting the concept of FS as a consistent phenomenon. Additionally, they may suggest potential avenues for future research to elucidate the origins of FS. Subsequent studies are essential to validate and expand upon these preliminary observations.


Assuntos
Eletroencefalografia , Convulsões , Humanos , Eletroencefalografia/métodos , Movimento
11.
Semin Hematol ; 61(2): 91-99, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38242773

RESUMO

Sequence convergence, otherwise stereotypy, of B-cell receptor immunoglobulin (BcR IG) from unrelated patients is a distinctive feature of the IG gene repertoire in chronic lymphocytic leukemia (CLL) whereby patients expressing a particular BcR IG archetype are classified into groups termed stereotyped subsets. From a biological perspective, the fact that a considerable fraction (∼41%) of patients with CLL express (quasi)identical or stereotyped BcR IG underscores the key role of antigen selection in the natural history of CLL. From a clinical perspective, at odds with the pronounced heterogeneity of CLL at large, patients belonging to the same stereotyped subset display consistent clinical presentation and outcome, including response to treatment, likely as a reflection of consistent biological background. Many major stereotyped subsets were recently shown to have satellites, that is, smaller subsets that are immunogenetically similar. Preliminary evidence supports that this similarity extends to shared biological and even clinical features, with important implications for patient stratification. Consequently, BcR IG stereotypy emerges as a powerful tool for dissecting the heterogeneity of CLL toward refined risk stratification and, eventually, more precise therapeutic interventions.


Assuntos
Leucemia Linfocítica Crônica de Células B , Receptores de Antígenos de Linfócitos B , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/genética , Humanos , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores de Antígenos de Linfócitos B/genética
12.
Vet Clin North Am Small Anim Pract ; 54(1): 71-85, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37805296

RESUMO

Repetitive behaviors in companion animals have been compared with obsessive-compulsive disorders in people. There is evidence that repetitive behaviors may go unrecognized because they have a high level of comorbidity with other, more salient, behavior problems and may be overshadowed or regarded as amusing eccentricities. To assess repetitive behavior problems, we propose a standardized approach involving 5 categories or axes. This approach aims to identify the nature of the problem and the balance among medical, environmental, and temperamental factors. Environmental modification, behavioral modification, and drug treatment are discussed.


Assuntos
Transtorno Obsessivo-Compulsivo , Cães , Animais , Transtorno Obsessivo-Compulsivo/terapia , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Comorbidade , Terapia Comportamental
13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013279

RESUMO

ObjectiveTo review the effect of response interruption and redirection intervention on vocal stereotypy in children with autism spectrum disorder (ASD). MethodsLiteratures on response interruption and redirection intervention for vocal stereotypy in children with ASD were retrieved from databases of EBSCO, PubMed, Web of Science, CNKI, and Wanfang data. The information of the literatures was extracted to conduct a scoping review. ResultsA total of 16 English literatures were included. All researches employed a single-subject time series study design. A total of 41 children with ASD were involved. Significant differences were found in levels of basic verbal functioning of children with ASD. Vocal stereotypy was characterized by both verbal and nonverbal forms. Most of the reviewed researches used experimental functional assessment to analyze the function of vocal stereotypy. In most cases, the function of vocal stereotypy was automatic reinforcement. Iwata et al.'s paradigm was dominantly adopted in performing experimental functional assessment across researches. Other related paradigms developed based on Iwata et al.'s paradigm to make operating process more concise were also used for experimental functional assessment in reviewed researches. Response disruption and redirection was often conducted in individualized setting, with a few researches conducted in special education classes. The time and frequency of interventions varied widely across subjects due to the levels of impairment in vocal stereotypy and other behaviors. According to a comparison of the effects of traditional response interruption and redirection and its morphing procedures, it was found that changing the content of the redirection task, reducing the number of redirection tasks, and varying the duration of execution did not impact the improvement of vocal stereotypy. Based on the comparisons of response interruption and redirection with matched stimuli, response cost, verbal manipulation training, and medication, it was found that both response interruption and redirection and other methods (except for medication) could reduce vocal stereotypy and promote the emergence of appropriate behaviors in children with ASD. Combining response interruption and redirection with other techniques, such as stimulus matching and response costs, yielded more favorable improvement of vocal stereotypy in children with ASD. ConclusionASD children with vocal stereotypy show different levels of functional language, and vocal stereotypy is generally characterized by both verbal and nonverbal formats. The function of vocal stereotypy is mostly automatic reinforcement. Response interruption and redirection as a behavioral intervention is mostly conducted in individualized setting, and the time and frequency of interventions depend on the levels of vocal stereotypy and other behaviors problems. Changing the content and number of redirection instructions does not significantly influence the improvement of vocal stereotypy in children with ASD. Other intervention methods such as matching stimulus and response cost are able to reduce vocal stereotypy in children with ASD, but response interruption and redirection used in conjunction with these methods show more favorable improvements. Response interruption and redirection interventions can not only reduce vocal stereotypy in children with ASD, but also increase appropriate vocalizations, task engagement and command obedience.

14.
Pharmacol Biochem Behav ; 233: 173658, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37804866

RESUMO

Schizophrenia is a chronic, debilitating mental illness that has not yet been completely understood. In this study, we aimed to investigate the effects of different doses of ketamine, a non-competitive NMDA receptor antagonist, on the positive- and negative-like symptoms of schizophrenia. We also explored whether these effects are related to changes in the immunoreactivity of GAD67, TH, and PPAR-γ in brain structures. To conduct the study, male mice received ketamine (20-40 mg/kg) or its vehicle (0.9 % NaCl) intraperitoneally for 14 consecutive days. We quantified stereotyped behavior, the time of immobility in the forced swimming test (FST), and locomotor activity after 7 or 14 days. In addition, we performed ex vivo analysis of the immunoreactivity of GAD, TH, and PPAR-γ, in brain tissues after 14 days. The results showed that ketamine administration for 14 days increased the grooming time in the nose region at all tested doses. It also increased immobility in the FST at 30 mg/kg doses and decreased the number of rearing cycles during stereotyped behavior at 40 mg/kg. These behavioral effects were not associated with changes in locomotor activity. We did not observe any significant alterations regarding the immunoreactivity of brain proteins. However, we found that GAD and TH were positively correlated with the number of rearing during the stereotyped behavior at doses of 20 and 30 mg/kg ketamine, respectively. GAD was positively correlated with the number of rearing in the open field test at a dose of 20 mg/kg. TH was inversely correlated with immobility time in the FST at a dose of 30 mg/kg. PPAR-γ was inversely correlated with the number of bouts of stereotyped behavior at a dose of 40 mg/kg of ketamine. In conclusion, the behavioral alterations induced by ketamine in positive-like symptoms were reproduced with all doses tested and appear to depend on the modulatory effects of TH, GAD, and PPAR-γ. Conversely, negative-like symptoms were associated with a specific dose of ketamine.


Assuntos
Ketamina , Esquizofrenia , Camundongos , Masculino , Animais , Ketamina/efeitos adversos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/induzido quimicamente , PPAR gama/metabolismo , Correlação de Dados , Natação , Comportamento Animal
15.
Psychodyn Psychiatry ; 51(3): 249-253, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37712664

RESUMO

Outside of specific motor conditions, bodily movements are rarely considered in contemporary psychiatry. Stereotypies and mannerisms in clinical cases of catatonia are seen as having no deeper meaning in contemporary psychiatry. Perhaps we are missing something that could be important for us and our patients. The psychiatrist and analyst Carl Jung suggested there was an unconscious communication, and therefore a meaning in psychotic symptoms, including the movements in catatonia. The unconscious is rarely considered in psychotic presentations, yet psychosis is a prevalent condition in clinical settings. In this article Jung's ideas are presented along with case examples that invite the reader to consider them in their own future practice.


Assuntos
Catatonia , Psiquiatria , Transtornos Psicóticos , Humanos , Comunicação , Movimento
16.
Medicina (Kaunas) ; 59(9)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37763786

RESUMO

Background and Objectives: To analyze the influence of parental presence and use of risperidone on social interaction and apathy among patients with Autism Spectrum Disorder (ASD). Materials and Methods: Cross-sectional study in a reference center for patients with ASD in a city in northeastern Brazil. The research was carried out using a sociodemographic questionnaire, the Dimensional Apathy Scale, and the Social Communication Questionnaire (SCQ) with the domains of social interaction, language, stereotypy, and communication. The referred questionnaire was answered by the parents or guardians of the children with ASD according to the DSM V criteria. Data were analyzed via independent t-test using the SPSS software version 20. Results: Interviews were conducted with 51 parents/guardians of autistic children with a mean age of 8.8 years (±2.95) and a predominance of males, 34 (66.7%). Of this total, 49 (96.1%) of the children attended school; 40 (78.4%) children were on medication, of which 38 (74.5%) were on risperidone. Those children on risperidone had a higher score on the SCQ scale (p = 0.049) and on the domain of stereotyped behaviors (p = 0.033), which indicated greater impairment. Another statistically relevant variable was the presence of married parents, whereby children who did not have the presence of married parents had a higher average of stereotyped behaviors compared to those who had married parents. Conclusions: The results showed differences in the means of social interactions for children on risperidone, especially regarding stereotyped behaviors. However, it is not possible to state whether this difference was due to the use of risperidone or whether they used risperidone precisely because of these behaviors. Also important was that children who had the presence of married parents showed fewer stereotyped behaviors. There was no difference in apathetic behavior between children.


Assuntos
Transtorno do Espectro Autista , Comportamento Estereotipado , Masculino , Humanos , Criança , Feminino , Estudos Transversais , Transtorno do Espectro Autista/complicações , Risperidona/uso terapêutico , Pais
18.
Proc Natl Acad Sci U S A ; 120(35): e2304323120, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37603735

RESUMO

The generation of appropriate behavioral responses involves dedicated neuronal circuits. The cortico-striatal-thalamo-cortical loop is especially important for the expression of motor routines and habits. Defects in this circuitry are closely linked to obsessive stereotypic behaviors, hallmarks of neuropsychiatric diseases including autism spectrum disorders (ASDs) and obsessive-compulsive disorders (OCDs). However, our knowledge of the essential synaptic machinery required to maintain balanced neurotransmission and plasticity within the cortico-striatal circuitry remains fragmentary. Mutations in the large synaptic scaffold protein intersectin1 (ITSN1) have been identified in patients presenting with ASD symptoms including stereotypic behaviors, although a causal relationship between stereotypic behavior and intersectin function has not been established. We report here that deletion of the two closely related proteins ITSN1 and ITSN2 leads to severe ASD/OCD-like behavioral alterations and defective cortico-striatal neurotransmission in knockout (KO) mice. Cortico-striatal function was compromised at multiple levels in ITSN1/2-depleted animals. Morphological analyses showed that the striatum of intersectin KO mice is decreased in size. Striatal neurons exhibit reduced complexity and an underdeveloped dendritic spine architecture. These morphological abnormalities correlate with defects in cortico-striatal neurotransmission and plasticity as well as reduced N-methyl-D-aspartate (NMDA) receptor currents as a consequence of postsynaptic NMDA receptor depletion. Our findings unravel a physiological role of intersectin in cortico-striatal neurotransmission to counteract ASD/OCD. Moreover, we delineate a molecular pathomechanism for the neuropsychiatric symptoms of patients carrying intersectin mutations that correlates with the observation that NMDA receptor dysfunction is a recurrent feature in the development of ASD/OCD-like symptoms.


Assuntos
Comportamento Compulsivo , Receptores de N-Metil-D-Aspartato , Animais , Camundongos , Receptores de N-Metil-D-Aspartato/genética , Comportamento Compulsivo/genética , Transmissão Sináptica , Camundongos Knockout
19.
eNeuro ; 10(8)2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37596047

RESUMO

One of the most prevalent deficits in autism spectrum disorder (ASD) are sensitivities to sensory stimuli. Despite the prevalence of sensory deficits in autism, there are few paradigms capable of easily assessing sensory behaviors in ASD-like mouse models. We addressed this need by creating the Somatosensory Nose-poke Adapted Paradigm (SNAP), which consists of an elevated platform with 6 holes in the center, half of which are lined with sandpaper and half are smooth, requiring mice to use their whiskers to sense the texture. The SNAP paradigm assesses tactile sensory preferences as well as stereotypy, anxiety, and locomotion. We used two wild-type (neurotypical) mouse strains, C57BL/6J (C57) inbred and CD-1 outbred mice, and two ASD mouse models, BTBR (a model of idiopathic ASD) and Cntnap2 -/- mice (a model of syndromic ASD). We found that both ASD models produced more nose pokes into the rough condition than the smooth condition, suggesting an increased preference for complex tactile stimulation when compared with the neurotypical groups, wherein no differences were observed. Furthermore, we found increased stereotypy and time spent in the center, suggestive of decreased anxiety, only for BTBR mice compared with the other mouse strains. Overall, SNAP is an easy to implement task to assess the degree of preference for complex tactile stimulation in ASD mouse models that can be further modified to exclude possible confounding effects of novelty or anxiety on the sensory preferences.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Animais , Camundongos , Camundongos Endogâmicos C57BL , Comportamento Estereotipado , Ansiedade , Modelos Animais de Doenças
20.
Biomedicines ; 11(7)2023 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-37509453

RESUMO

Research into genetic and physiological mechanisms of widespread disorders such as arterial hypertension as well as neuropsychiatric and other human diseases is urgently needed in academic and practical medicine and in the field of biology. Nevertheless, such studies have many limitations and pose difficulties that can be overcome by using animal models. To date, for the purposes of creating animal models of human pathologies, several approaches have been used: pharmacological/chemical intervention; surgical procedures; genetic technologies for creating transgenic animals, knockouts, or knockdowns; and breeding. Although some of these approaches are good for certain research aims, they have many drawbacks, the greatest being a strong perturbation (in a biological system) that, along with the expected effect, exerts side effects in the study. Therefore, for investigating the pathogenesis of a disease, models obtained using genetic selection for a target trait are of high value as this approach allows for the creation of a model with a "natural" manifestation of the pathology. In this review, three rat models are described: ISIAH rats (arterial hypertension), GC rats (catatonia), and PM rats (audiogenic epilepsy), which are developed by breeding in the Laboratory of Evolutionary Genetics at the Institute of Cytology and Genetics (the Siberian Branch of the Russian Academy of Sciences).

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