Striatal Syntaixin 1A Plays a Protective Role Against Iminodipropionitrile Induced Tic Disorder Through Interaction with Dopamine Transporter

An important mechanism of Tic disorder (TD) is dysfunction in the dopamine (DA) system. Our pilot observation found the expression of Syntaxin 1A (STX1A), a presynaptic SNARE complex, changed in the striatum of TD animals. The present study aimed to clarify the biological role of striatal STX1A in the pathological state of TD and the specific mechanism of its regulation of the dopaminergic system. The TD rat model was established using iminodipropionitrile (IDPN). Adenovirus was used to modulate the expression of STX1A and dopamine transporter (DAT) in vivo and vitro. Primary culture of striatal dopaminergic neurons was performed for in-vitro observation of the DA reuptake, CO-IP analysis of the interaction between STX1A and DAT. First, using immunofluorescence staining, Western blotting, and qPCR, we found that the IDPN induced TD model had reduced striatal STX1A expression. In vitro, the DA content in the supernatant was significantly lower in the STX1A overexpressed group, and the intracellular DA content was significantly higher. Overexpression of STX1A in vivo partially counteracts the IDPN-induced TD-like behaviors, including bite time and head shaking time. Meanwhile, in-vivo knockdown of STX1A can aggravates TD-like behaviors. Further, DAT was overexpressed in vivo, and the TD-like behavior was alleviated. Interestingly, overexpression of DAT in the striatum resulted in increased levels of STX1A. In order to clarify the interaction between DAT and STX1A, the CO-IP analysis was conducted based on the protein of purified striatal dopaminergic neurons. Compared to the IgG control, the blots of DAT and STX1A showed significant binding of each other. Striatal STX1A expression is decreased in TD development, and STX1A plays an anti-TD role possibly through interaction with DAT, which maintains the DA reuptake. The exorbitant DA signal caused by STX1A inhibition drives the pathological stereotyped behavior.

Effects of Chemogenetic Inhibition of D1 or D2 Receptor-Containing Neurons of the Substantia Nigra and Striatum in Mice With Tourette Syndrome

As tourette syndrome (TS) is a common neurobehavioral disorder, the primary symptoms of which include behavioral stereotypies. Dysfunction of the substantia nigra–striatum network could be the main pathogenesis of TS, which is closely associated with dopamine (DA) and its receptors. TS is often resistant to conventional treatments. Therefore, it is necessary to investigate the neurobiological mechanisms underlying its pathogenesis. In this study, we investigated whether chemogenetic activation or inhibition of dopaminergic D1 receptor (D1R)- or D2 receptor (D2R)-containing neurons in the substantia nigra pars compacta (SNpc) or dorsal striatum (dSTR) affected the stereotyped behavior and motor functions of TS mice. Intraperitoneal injection of 3,3′-iminodipropionitrile (IDPN) was used to induce TS in mice. Stereotyped behavior test and open-field, rotarod, and grip strength tests were performed to evaluate stereotyped behavior and motor functions, respectively. Immunofluorescence labeling was used to detect the co-labeling of virus fluorescence and D1R or D2R. We found that chemogenetic inhibition of D1R- or D2R-containing neurons in the SNpc and dSTR alleviated behavioral stereotypies and motor functions in TS mice. Chemogenetic activation of D1R-containing neurons in the dSTR aggravated behavioral stereotypies and motor functions in vehicle-treated mice, but neither was aggravated in TS mice. In conclusion, chemogenetic inhibition of D1R- or D2R-containing neurons in the SNpc and dSTR alleviated behavioral stereotypies of TS, providing a new treatment target for TS. Moreover, the activation of D1R-containing neurons in the dSTR may contribute to the pathogenesis of TS, which can be chosen as a more precise target for treatment.

Meme and cyber sexism: Habitus and symbolic violence of patriarchy on the Internet

This study examines the various sexist practices on the Internet called cyber sexism. The Internet seems to become a new world for patriarchal domination. The amount of content, comments, and memes circulating on the Internet and social media, such as Instagram, Facebook, Twitter, and WhatsApp harassing women, is proof of the patriarchal power on the Internet. This study used a qualitative method with a feminist perspective, collecting memes through Instagram, Facebook, Twitter, and WhatsApp. The memes were then reviewed and interpreted to find their meaning. Using Pierre Bourdieu’s habitus theory and symbolic violence, memes were analyzed to find the factors that cause sexism against women and the logical link between sexist practices in the real world and cyber sexism on the Internet. Results indicate that people’s habitus about patriarchy has become a mental structure of society that influences stereotyped behavior and gender bias and plays an important role in sexism on the Internet. The Internet, as an arena, has become the initial capital for men to dominate. Naming and mentioning women in various memes are the forms of symbolic violence against them that form new sexist habitus on the Internet.

N-Methyl-d-aspartate (NMDA) receptor antibody in relation to autism spectrum disorder (ASD): presence and association with symptom profile

Background Several studies pointed to immune dysregulation abnormalities linked to autism spectrum disorders (ASD). Of those, several autoantibodies had been identified. Recent findings of N-methyl d-aspartate (NMDA) antibodies in autoimmune encephalitis suggested that it caused symptoms like autistic regression. Thus, the purpose of the study was to test for the presence of anti-NMDAR antibodies in the ASD disorder population and to correlate this with the clinical findings. Results Eighty-seven autistic children, 4–12 years old, were enrolled in the study and were matched with sixty typically developing children used as controls. The diagnosis of cases was confirmed by ADOS-2 and clinical evaluation. None of the control children had positive anti-NMDAR antibodies, while 26.4% (23 children) of the patients’ group were positive for serum anti-NMDA receptor antibodies (> 200 pg/ml, p = 0.0157). The positive anti-NMDAR antibody was statistically correlated with better speech stage (p = 0.017), more severe stereotyped behavior (p ≤ 0.001), and abnormal EEG findings (p = 0.025). Conclusions There is a possibility of the presence of anti-NMDAR antibodies in the autism spectrum disorder population with certain characteristics, especially the severity of the stereotyped behaviors.

Self-grooming promotes social interaction in mice via chemosensory communication

Self-grooming is a stereotyped behavior displayed by nearly all animals. Among other established functions, self-grooming is implicated in social communication in some animals. However, whether self-grooming specifically influences behaviors of nearby individuals has not been directly tested, partly due to the technical challenge of inducing self-grooming in a reliable and temporally controllable manner. We recently found that optogenetic activation of dopamine D3 receptor expressing neurons in the ventral striatal islands of Calleja robustly induces orofacial grooming in mice. Using this optogenetic manipulation, here we demonstrate that observer mice display social preference for grooming over non-grooming mice regardless of biological sex. Moreover, grooming-induced social attraction depends on volatile chemosensory cues broadcasted from grooming mice. Collectively, our study establishes self-grooming as a means of promoting social interaction among mice via volatile cues, suggesting an additional benefit for animals to allocate a significant amount of time to this behavior.

Constitutive depletion of brain serotonin differentially affects rats' social and cognitive abilities

Background: Central serotonin is an essential neuromodulator for mental disorders. It appears a promising transdiagnostic marker of distinct psychiatric disorders and a common modulator of some of their key behavioral symptoms. We aimed to identify the behavioral markers of serotonergic function in rats and compare them to human deficits. Methods: We applied a comprehensive profiling approach in adult male Tph2-/- rats constitutively lacking central serotonin. Under classical and ethological testing conditions, we tested each individual's cognitive, social and non-social abilities and characterized the group organization (i.e. social network, hierarchy). Using unsupervised machine learning, we identified the functions most dependent on central serotonin. Results: In classical procedures, Tph2-/- rats presented an unexpected normal cognitive profile. Under the complex and experimenter-free conditions of their home-cage, the same Tph2-/- rats presented drastic changes in their daily life. Brain serotonin depletion induced compulsive aggression and sexual behavior, hyperactive and hypervigilant stereotyped behavior, reduced self-care and body weight, and exacerbated corticosterone levels. Group-housed Tph2-/- rats showed strong social disorganization with disrupted social networks and hierarchical structure, which may arise from communication deficits and cognitive blunting. Conclusions: Serotonin depletion induced a profile reminiscent of the symptomatology of impulse control and anxiety disorders. Serotonin was necessary for behavioral adaptation to dynamic social environments. In classical testing conditions, our animal model challenged the concept of an essential role of serotonin in decision-making, flexibility, and impulsivity, although developmental compensations may have occurred. These contrasting findings highlight the need to generalize the evaluation of animal models' multidimensional functions within the complexity of the social living environment.

Changes in the Number and Morphology of Dendritic Spines in the Hippocampus and Prefrontal Cortex of the C58/J Mouse Model of Autism

Autism spectrum disorder (ASD) has a broad range of neurobiological characteristics, including alterations in dendritic spines, where approximately 90% of excitatory synapses occur. Therefore, changes in their number or morphology would be related to atypical brain communication. The C58/J inbred mouse strain displays low sociability, impaired communication, and stereotyped behavior; hence, it is considered among the animal models suitable for the study of idiopathic autism. Thus, this study aimed to evaluate the dendritic spine differences in the hippocampus and the prefrontal cortex of C58/J mice. We found changes in the number of spines and morphology in a brain region-dependent manner: a subtle decrease in spine density in the prefrontal cortex, higher frequency of immature phenotype spines characterized by filopodia-like length or small morphology, and a lower number of mature phenotype spines with mushroom-like or wide heads in the hippocampus. Moreover, an in silico analysis showed single nucleotide polymorphisms (SNPs) at genes collectively involved in regulating structural plasticity with a likely association with ASD, including MAP1A (Microtubule-Associated Protein 1A), GRM7 (Metabotropic Glutamate Receptor, 7), ANKRD11 (Ankyrin Repeat Domain 11), and SLC6A4 (Solute Carrier Family 6, member 4), which might support the relationship between the C58/J strain genome, an autistic-like behavior, and the observed anomalies in the dendritic spines.

Absence of covert face valuation in Autism

Autism is a neurodevelopmental condition defined on clinical criteria related to diminished social reciprocity and stereotyped behavior. An influential view explains autism as a social motivation disorder characterized by less attention paid to the social environment and less pleasure experienced with social rewards. However, experimental attempts to validate this theory, by testing the impact of social reward on behavioral choice and brain activity, has yielded mixed results, possibly due to variations in how explicit instructions were about task goals. Here, we specified the putative motivation deficit as an absence of spontaneous valuation in the social domain, unexplained by inattention and correctible by explicit instruction. Since such deficit cannot be assessed with behavioral measures, we used functional neuroimaging (fMRI) to readout covert subjective values, assigned to social and nonsocial stimuli (faces and objects), either explicitly asked to participants (during a likeability judgment task) or not (during age or size estimation tasks). Value-related neural activity observed for objects, or for faces under explicit instructions, was very similar in autistic and control participants, with an activation peak in the ventromedial prefrontal cortex (vmPFC), known as a key node of the brain valuation system. The only difference observed in autistic participants was an absence of the spontaneous valuation normally triggered by faces, even when they were attended for age estimation. Our findings, therefore, suggest that in autism, social stimuli might fail to trigger the automatic activation of the brain valuation system.

PSYCHOMOTRICITY AND AUTISM SPECTRUM DISORDER

Autism spectrum disorder is considered to be a global problem, as it has no definitive treatment, with unknown etiology, complexity of diagnosis and increasing spread throughout the world and in Algeria in particular.The latest version of the DSM-5 is based on two diagnostic criteria: lack of communication and social interaction; stereotyped behavior and restricted interests. Diagnosis is carried out by a team of specialists by collecting information, applying tests, and establishing a differential diagnosis. The efforts of specialists and researchers have contributed to the development of ways to take care of children with this disorder, as it helps them develop their skills and increase their independence and integration into society. Among these therapeutic interventions, we find psychomotor therapy, as the subject of this research. Psychomotricity consists of a specific practice focusing on the body, with the aim of alleviating sensorimotor and psychomotor disorders which are sometimes very disabling. The technique of playing is widely used according to the principles of kinetic psychology. The purpos of this paper is to make autism, its diagnosis and intervention methods known and to prove the efficiency of psychomotor intervention by analyzing the scientific literature. The importance of this topic lies in its enrichment of the literary balance, given its treatment of an important issue for society, and it’s interesting on the psychomotor intervention that is highly relied upon in the centers of care for children with autism, and an important return in terms of the development of their abilities.