Supplemental Material for Repetitive Behavior With Objects in Infants Developing Autism Predicts Diagnosis and Later Social Behavior as Early as 9 Months

Introduction: A neurodevelopmental disorder, autism typically identified with three primary behavioral consequences, such as social impairment, communication problems and limited or stereotypical behavior. Because of its co-morbidity and lack of therapeutic options, autism is a global economic burden. A short chain of fatty acid, propionic acid formed biologically by gut microbiome. Propionic acid levels that are too high can cause leaky intestines, which can lead to autism-like symptoms. Methods: To induce autism, male Albino Wistar rats were given propionic acid (250 mg/kg / po on the 21st, 22nd, and 23rd postnatal days). Rats were also received a ryanodine receptor antagonist (Ruthenium red: 3 mg/kg/po; postnatal 21st to 50th day) to see what influence it had on the propionic acid-induced autism. Anxiety, social behavior, and repeated behaviors were all assessed, as well as oxidative stress, inflammatory indicators, neuro signaling proteins, and blood brain barrier permeability. Results: Ruthenium red was found to counter the propionic acid induced increases in anxiety, repetitive behavior prefrontal cortex levels of IL-6, TNF-α, TBARS, Evans blue leakage and water content along with decreases in social behavior, IL-10, and GSH followed by hippocampus CREB and BDNF levels. Conclusion: Ryanodine receptor antagonist presented neuroprotective effect in propionic acid induced conditions like autism by modulatory effects on social and repetitive behavior, oxidative stress, neuroinflammation, and neuroprotein changes. Ryanodine receptors can be further explored in depth to manage autism as a condition.

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Repetitive behavior with objects in infants developing autism predicts diagnosis and later social behavior as early as 9 months.

Journal of Abnormal Psychology ◽

10.1037/abn0000692 ◽

2021 ◽

Vol 130 (6) ◽

pp. 665-675

Author(s):

Meghan Miller ◽

Shuai Sun ◽

Ana-Maria Iosif ◽

Gregory S. Young ◽

Ashleigh Belding ◽

...

Keyword(s):

Social Behavior ◽

Repetitive Behavior

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Social-like responses are inducible in asocial Mexican cavefish despite the exhibition of strong repetitive behavior

eLife ◽

10.7554/elife.72463 ◽

2021 ◽

Vol 10 ◽

Author(s):

Motoko Iwashita ◽

Masato Yoshizawa

Keyword(s):

Social Behavior ◽

Antipsychotic Drug ◽

Drug Targeting ◽

Dopaminergic System ◽

Repetitive Behavior ◽

Astyanax Mexicanus ◽

Social Ability ◽

Social Species ◽

Social Abilities ◽

Blind Cavefish

Social behavior is a hallmark of complex animal systems; however, some species appear to have secondarily lost this social ability. In these non-social species, whether social abilities are permanently lost or suppressed is unclear. The blind cavefish Astyanax mexicanus is known to be asocial. Here, we reveal that cavefish exhibited social-like interactions in familiar environments but suppressed these interactions in stress-associated unfamiliar environments. Furthermore, the level of suppression in sociality was positively correlated with that of stereotypic repetitive behavior, as seen in mammals. Treatment with a human antipsychotic drug targeting the dopaminergic system induced social-like interactions in cavefish, even in unfamiliar environments, while reducing repetitive behavior. Overall, these results suggest that the antagonistic association between repetitive and social-like behaviors is deeply shared from teleosts through mammals.

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Maternal Immune Activation Causes Social Behavior Deficits and Hypomyelination in Male Rat Offspring with an Autism-Like Microbiota Profile

Brain Sciences ◽

10.3390/brainsci11081085 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1085

Author(s):

Gilbert Aaron Lee ◽

Yen-Kuang Lin ◽

Jing-Huei Lai ◽

Yu-Chun Lo ◽

Yu-Chen S. H. Yang ◽

...

Keyword(s):

Social Behavior ◽

Gut Microbiota ◽

Immune Activation ◽

Repetitive Behavior ◽

Fecal Microbiota ◽

Autism Spectrum ◽

Male Rat ◽

Maternal Immune Activation ◽

Rat Offspring ◽

Microbial Dysbiosis

Maternal immune activation (MIA) increases the risk of autism spectrum disorder (ASD) in offspring. Microbial dysbiosis is associated with ASD symptoms. However, the alterations in the brain–gut–microbiota axis in lipopolysaccharide (LPS)-induced MIA offspring remain unclear. Here, we examined the social behavior, anxiety-like and repetitive behavior, microbiota profile, and myelination levels in LPS-induced MIA rat offspring. Compared with control offspring, MIA male rat offspring spent less time in an active social interaction with stranger rats, displayed more anxiety-like and repetitive behavior, and had more hypomyelination in the prefrontal cortex and thalamic nucleus. A fecal microbiota analysis revealed that MIA offspring had a higher abundance of Alistipes, Fusobacterium, and Ruminococcus and a lower abundance of Coprococcus, Erysipelotrichaies, and Actinobacteria than control offspring, which is consistent with that of humans with ASD. The least absolute shrinkage and selection operator (LASSO) method was applied to determine the relative importance of the microbiota, which indicated that the abundance of Alistipes and Actinobacteria was the most relevant for the profile of defective social behavior, whereas Fusobacterium and Coprococcus was associated with anxiety-like and repetitive behavior. In summary, LPS-induced MIA offspring showed an abnormal brain–gut–microbiota axis with social behavior deficits, anxiety-like and repetitive behavior, hypomyelination, and an ASD-like microbiota profile.

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Germline nuclear-predominant Pten murine model exhibits impaired social and perseverative behavior, microglial activation, and increased oxytocinergic activity

Molecular Autism ◽

10.1186/s13229-021-00448-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Nick Sarn ◽

Stetson Thacker ◽

Hyunpil Lee ◽

Charis Eng

Keyword(s):

Social Behavior ◽

Microglial Activation ◽

Repetitive Behavior ◽

Suppressor Gene ◽

Autism Spectrum ◽

Animal Modeling ◽

Therapeutic Modalities ◽

Downstream Effects

Abstract Background Autism spectrum disorder (ASD) has a strong genetic etiology. Germline mutation in the tumor suppressor gene PTEN is one of the best described monogenic risk cases for ASD. Animal modeling of cell-specific Pten loss or mutation has provided insight into how disruptions to the function of PTEN affect neurodevelopment, neurobiology, and social behavior. As such, there is a growing need to understand more about how various aspects of PTEN activity and cell-compartment-specific functions, contribute to certain neurological or behavior phenotypes. Methods To understand more about the relationship between Pten localization and downstream effects on neurophenotypes, we generated the nuclear-predominant PtenY68H/+ mouse, which is identical to the genotype of some PTEN-ASD individuals. We subjected the PtenY68H/+ mouse to morphological and behavioral phenotyping, including the three-chamber sociability, open field, rotarod, and marble burying tests. We subsequently performed in vivo and in vitro cellular phenotyping and concluded the work with a transcriptomic survey of the PtenY68H/+ cortex, which profiled gene expression. Results We observe a significant increase in P-Akt downstream of canonical Pten signaling, macrocephaly, decreased sociability, decreased preference for novel social stimuli, increased repetitive behavior, and increased thigmotaxis in PtenY68H/+ six-week-old (P40) mice. In addition, we found significant microglial activation with increased expression of complement and neuroinflammatory proteins in vivo and in vitro accompanied by enhanced phagocytosis. These observations were subsequently validated with RNA-seq and qRT-PCR, which revealed overexpression of many genes involved in neuroinflammation and neuronal function, including oxytocin. Oxytocin transcript was fivefold overexpressed (P = 0.0018), and oxytocin protein was strongly overexpressed in the PtenY68H/+ hypothalamus. Conclusions The nuclear-predominant PtenY68H/+ model has clarified that Pten dysfunction links to microglial pathology and this associates with increased Akt signaling. We also demonstrate that Pten dysfunction associates with changes in the oxytocin system, an important connection between a prominent ASD risk gene and a potent neuroendocrine regulator of social behavior. These cellular and molecular pathologies may related to the observed changes in social behavior. Ultimately, the findings from this work may reveal important biomarkers and/or novel therapeutic modalities that could be explored in individuals with germline mutations in PTEN with ASD.

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Examining criterion-oriented validity of the Repetitive Behavior Scales for Early Childhood (RBS-EC) and the Video-Referenced Rating of Reciprocal Social Behavior (vrRSB)

Development and Psychopathology ◽

10.1017/s0954579419001159 ◽

2019 ◽

Vol 32 (3) ◽

pp. 779-789 ◽

Cited By ~ 1

Author(s):

Carolyn Lasch ◽

Jason J. Wolff ◽

Jed T. Elison

Keyword(s):

Early Childhood ◽

Social Behavior ◽

Discriminant Validity ◽

Repetitive Behavior ◽

Parent Report ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Social Emotional ◽

Restricted Interests ◽

Behavioral Assessments

AbstractImproved characterization of quantitative traits and dimensionally distributed complex behaviors during toddlerhood may improve early identification of autism spectrum disorder and related neurodevelopmental disorders. Parents of 205 community-ascertained toddlers (age: mean = 20.2, SD = 2.6 months) completed the Repetitive Behavior Scales for Early Childhood (RBS-EC) and the Video-Referenced Rating of Reciprocal Social Behavior (vrRSB), with longitudinal follow-up of behavioral assessments and/or another round of parent-report questionnaires. Criterion validity was examined both concurrently and longitudinally using the Infant Toddler Social Emotional Assessment (ITSEA) as a criterion anchor. Reciprocal social behavior as measured by the vrRSB was significantly associated with social competence as measured by the ITSEA, longitudinally and concurrently. Reciprocal social behavior was not associated with the externalizing subscale on the ITSEA, providing evidence of discriminant validity. Higher-order repetitive behaviors (restricted interests; rituals and routines) as measured by RBS-EC subscales were associated with the dysregulation and internalizing subscales of the ITSEA, longitudinally and concurrently. All RBS-EC subscales (excepting repetitive motor) were associated concurrently and longitudinally with the dysregulation subscale of the ITSEA. We report evidence of criterion-oriented and discriminant validity for the constructs/domains captured by the RBS-EC and vrRSB. These instruments may be particularly useful in characterizing dimensional variability across the typical-to-atypical continuum.

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