Stereotypy Research Articles

Effectiveness of animal-assisted activities and therapies for autism spectrum disorder: a systematic review and meta-analysis.

Given the rising interest in complementary therapeutic strategies for autism spectrum disorder (ASD), this research aims to provide a comprehensive analysis of the impact of animal-assisted activities and therapies (AAAT) on various ASD symptoms. A meticulous search of databases, including Scopus and PubMed, was conducted to gather relevant research on AAAT for ASD. This process led to the selection of 45 studies encompassing 1,212 participants. The chosen studies were then subjected to a meta-analysis to evaluate the efficacy of AAAT in alleviating core ASD symptoms. The meta-analysis revealed significant improvements in several core ASD symptoms due to AAAT. Notably, there were improvements in social communication (MD = -4.96, 95% CI [-7.49, -2.44]), irritability (MD = -2.38, 95% CI [-4.06, -0.71]), hyperactivity (MD = -4.03, 95% CI [-6.17, -1.89]), and different word usage skills (MD = 20.48, 95% CI [7.41, 33.55]). However, social awareness (MD = -1.63, 95% CI [-4.07, 0.81]), social cognition (MD = -3.60, 95% CI [-9.36, 2.17]), social mannerisms (MD = -0.73, 95% CI [-2.55, 1.09]), social motivation (MD = -1.21, 95% CI [-2.56, 0.13]), lethargy (MD = -1.12, 95% CI [-3.92, 1.68]), and stereotypical behaviors (MD = -0.23, 95% CI [-1.27, 0.80]) did not significantly improve. The study demonstrates the potential of AAAT in improving certain core symptoms of ASD, such as social communication, irritability, hyperactivity, and word usage skills. However, the effectiveness of AAAT in other ASD symptom domains remains uncertain. The research is limited by the absence of long-term follow-up data and a high risk of bias in existing studies. Therefore, while the findings indicate the promise of AAAT in specific areas, caution is advised in generalizing its efficacy across all ASD symptoms.

CELF2 Deficiency Demonstrates Autism-Like Behaviors and Interferes with Late Development of Cortical Neurons in Mice.

CELF2 variants have been linked to neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD). However, the molecular mechanisms remain unclear. We generated Celf2 Nestin-Cre knockout mice.Our findings revealed that Celf2 Nestin-Cre heterozygous knockout mice exhibited social impairment and anxiety, an autism-like behavior, though no manifestations of repetitive stereotyped behavior, learning cognitive impairment, or depression were observed. Immunofluorescence assay showed an underdeveloped cerebral cortex with significantly reduced cortical thickness, albeit without abnormal cell density. Further in vitro neuronal culture demonstrated a significant reduction in dendritic spine density and affected synaptic maturation in Celf2 deficient mice, with no notable abnormalities in total neurite and axon length. RNA-seq and RIP-seq analysis of the cerebral cortex revealed differentially expressed genes post Celf2 gene knockout compared with the control group. Enrichment analysis highlighted significant enrichment in dendrite and synapse-related biological processes and pathways. Our study delineated the behavioral and neurodevelopmental phenotypes of Celf2, suggesting its potential involvement in autism through the regulation of target genes associated with dendritic spines and synapse development. Further research is needed to elucidate the specific mechanisms involved.

Developmental Disruption of Mef2c in Medial Ganglionic Eminence–Derived Cortical Inhibitory Interneurons Impairs Cellular and Circuit Function

BackgroundMEF2C is strongly linked to various neurodevelopmental disorders including autism, intellectual disability, schizophrenia, and attention-deficit/hyperactivity disorder. Mice that constitutively lack 1 copy of Mef2c or selectively lack both copies of Mef2c in cortical excitatory neurons display a variety of behavioral phenotypes associated with neurodevelopmental disorders. The MEF2C protein is a transcription factor necessary for cellular development and synaptic modulation of excitatory neurons. MEF2C is also expressed in a subset of cortical GABAergic (gamma-aminobutyric acidergic) inhibitory neurons, but its function in those cell types remains largely unknown. MethodsUsing conditional deletions of the Mef2c gene in mice, we investigated the role of MEF2C in parvalbumin-expressing interneurons (PV-INs), the largest subpopulation of cortical GABAergic cells, at 2 developmental time points. We performed slice electrophysiology, in vivo recordings, and behavior assays to test how embryonic and late postnatal loss of MEF2C from GABAergic INs impacts their survival and maturation and alters brain function and behavior. ResultsLoss of MEF2C from PV-INs during embryonic, but not late postnatal, development resulted in reduced PV-IN number and failure of PV-INs to molecularly and synaptically mature. In association with these deficits, early loss of MEF2C in GABAergic INs led to abnormal cortical network activity, hyperactive and stereotypic behavior, and impaired cognitive and social behavior. ConclusionsMEF2C expression is critical for the development of cortical GABAergic INs, particularly PV-INs. Embryonic loss of function of MEF2C mediates dysfunction of GABAergic INs, leading to altered in vivo patterns of cortical activity and behavioral phenotypes associated with neurodevelopmental disorders.

SEP-363856 exerts neuroprotection through the PI3K/AKT/GSK-3β signaling pathway in a dual-hit neurodevelopmental model of schizophrenia-like mice.

Schizophrenia (SZ) is a serious, destructive neurodevelopmental disorder. Antipsychotic medications are the primary therapy approach for this illness, but it's important to pay attention to the adverse effects as well. Clinical studies for SZ are currently in phase ΙΙΙ for SEP-363856 (SEP-856)-a new antipsychotic that doesn't work on dopamine D2 receptors. However, the underlying action mechanism of SEP-856 remains unknown. This study aimed to evaluate the impact and underlying mechanisms of SEP-856 on SZ-like behavior in a perinatal MK-801 treatment combined with social isolation from the weaning to adulthood model (MK-SI). First, we created an animal model that resembles SZ that combines the perinatal MK-801 with social isolation from weaning to adulthood. Then, different classical behavioral tests were used to evaluate the antipsychotic properties of SEP-856. The levels of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β), apoptosis-related genes (Bax and Bcl-2), and synaptic plasticity-related genes (brain-derived neurotrophic factor [BDNF] and PSD-95) in the hippocampus were analyzed by quantitative real-time PCR. Hematoxylin and eosin staining were used to observe the morphology of neurons in the hippocampal DG subregions. Western blot was performed to detect the protein expression levels of BDNF, PSD-95, Bax, Bcl-2, PI3K, p-PI3K, AKT, p-AKT, GSK-3β, p-GSK-3β in the hippocampus. MK-SI neurodevelopmental disease model studies have shown that compared with sham group, MK-SI group exhibit higher levels of autonomic activity, stereotyped behaviors, withdrawal from social interactions, dysregulated sensorimotor gating, and impaired recognition and spatial memory. These findings imply that the MK-SI model can mimic symptoms similar to those of SZ. Compared with the MK-SI model, high doses of SEP-856 all significantly reduced increased activity, improved social interaction, reduced stereotyping behavior, reversed sensorimotor gating dysregulation, and improved recognition memory and spatial memory impairment in MK-SI mice. In addition, SEP-856 can reduce the release of proinflammatory factors in the MK-SI model, promote the expression of BDNF and PSD-95 in the hippocampus, correct the Bax/Bcl-2 imbalance, turn on the PI3K/AKT/GSK-3β signaling pathway, and ultimately help the MK-SI mice's behavioral abnormalities. SEP-856 may play an antipsychotic role in MK-SI "dual-hit" model-induced SZ-like behavior mice by promoting synaptic plasticity recovery, decreasing death of hippocampal neurons, lowering the production of pro-inflammatory substances in the hippocampal region, and subsequently initiating the PI3K/AKT/GSK-3β signaling cascade.

Role of FMRP in AKT/mTOR pathway-mediated hippocampal autophagy in fragile X syndrome

Fragile X syndrome (FXS) is caused by epigenetic silencing of the Fmr1 gene, leading to the deletion of the coding protein FMRP. FXS induces abnormal hippocampal autophagy and mTOR overactivation. However, it remains unclear whether FMRP regulates hippocampal autophagy through the AKT/mTOR pathway, which influences the neural behavior of FXS. Our study revealed that FMRP deficiency increased the protein levels of p-ULK-1 and p62 and decreased LC3II/LC3I level in Fmr1 knockout (KO) mice. The mouse hippocampal neuronal cell line HT22 with knockdown of Fmr1 by lentivirus showed that the protein levels of p-ULK-1 and p62 were increased, whereas LC3II/LC3I was unchanged. Further observations revealed that FMRP deficiency obstructed autophagic flow in HT22 cells. Therefore, FMRP deficiency inhibited autophagy in the mouse hippocampus and HT22 cells. Moreover, FMRP deficiency increased reactive oxygen species (ROS) level, decreased the co-localization between the mitochondrial outer membrane proteins TOM20 and LC3 in HT22 cells, and caused a decrease in the mitochondrial autophagy protein PINK1 in HT22 cells and Fmr1 KO mice, indicating that FMRP deficiency caused mitochondrial autophagy disorder in HT22 cells and Fmr1 KO mice. To explore the mechanism by which FMRP deficiency inhibits autophagy, we examined the AKT/mTOR signaling pathway in the hippocampus of Fmr1 KO mice, found that FMRP deficiency caused overactivation of the AKT/mTOR pathway. Rapamycin-mediated mTOR inhibition activated and enhanced mitochondrial autophagy. Finally, we examined whether rapamycin affected the neurobehavior of Fmr1 KO mice. The Fmr1 KO mice exhibited stereotypical behavior, impaired social ability, and learning and memory impairment, while rapamycin treatment improved behavioral disorders in Fmr1 KO mice. Thus, our study revealed the molecular mechanism by which FMRP regulates autophagy function, clarifying the role of hippocampal neuron mitochondrial autophagy in the pathogenesis of FXS, and providing novel insights into potential therapeutic targets of FXS.

Equine-assisted services for motor outcomes of autistic children: A systematic review.

Equine-assisted services use various aspects of horses, like their movement, warmth, and size, to enhance individuals' overall well-being. Many studies have underscored the positive impact of equine-assisted services on autistic children, affecting areas such as social interaction, communication, engagement, stereotypical behaviors, and motor functions. Given the growing recognition of motor functions as clinical specifiers in autism, it is imperative to specifically investigate how equine-assisted services influence these outcomes. To address this, we conducted a systematic review to synthesize existing literature on the effects of equine-assisted services on motor outcomes of autistic children. Our review encompassed study characteristics, features of equine-assisted service interventions, and major motor outcomes. We also evaluated the methodological quality of the equine-assisted service studies to offer insights for future research directions. Through thorough database searches and the use of the standardized procedure of conducting a systematic review (The Preferred Reporting Items for Systematic Reviews and Meta-analyses), 12 research studies were identified and included. These studies reported the effects of various equine-assisted service types (such as therapy, horsemanship, or learning) on motor outcomes of autistic children. Significant enhancements in coordination, strength, balance, posture, and overall motor skills indicate the effectiveness of equine-assisted services in improving motor outcomes of autistic children. Building on these findings, we provide recommendations for future research endeavors aimed at enhancing the reliability and validity of using equine-assisted services to improve motor outcomes of autistic children. This work contributes to a deeper understanding of how equine-assisted services can benefit this population and guides the development of more effective equine-assisted service interventions.

Human-derived fecal microbiota transplantation alleviates social deficits of the BTBR mouse model of autism through a potential mechanism involving vitamin B6 metabolism.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficiencies and stereotypic behaviors influenced by hereditary and/or environmental risk factors. There are currently no approved medications for treating the core symptoms of ASD. Human fecal microbiota transplantation (FMT) has emerged as a potential intervention to improve autistic symptoms, but the underlying mechanisms are not fully understood. In this study, we evaluated the effects of human-derived FMT on behavioral and multi-omics profiles of the BTBR mice, an established model for ASD. FMT effectively alleviated the social deficits in the BTBR mice and normalized their distinct plasma metabolic profile, notably reducing the elevated long-chain acylcarnitines. Integrative analysis linked these phenotypic changes to specific Bacteroides species and vitamin B6 metabolism. Indeed, vitamin B6 supplementation improved the social behaviors in BTBR mice. Collectively, these findings shed new light on the interplay between FMT and vitamin B6 metabolism and revealed a potential mechanism underlying the therapeutic role of FMT in ASD.IMPORTANCEAccumulating evidence supports the beneficial effects of human fecal microbiota transplantation (FMT) on symptoms associated with autism spectrum disorder (ASD). However, the precise mechanism by which FMT induces a shift in the microbiota and leads to symptom improvement remains incompletely understood. This study integrated data from colon-content metagenomics, colon-content metabolomics, and plasma metabolomics to investigate the effects of FMT treatment on the BTBR mouse model for ASD. The analysis linked the amelioration of social deficits following FMT treatment to the restoration of mitochondrial function and the modulation of vitamin B6 metabolism. Bacterial species and compounds with beneficial roles in vitamin B6 metabolism and mitochondrial function may further contribute to improving FMT products and designing novel therapies for ASD treatment.

Do cows with stereotypic tongue-rolling behaviour cope better with their environment?

Stereotypic behaviours, especially oral stereotypic behaviours, are frequently expressed in farm animals. Tongue-rolling is the most common oral stereotypic behaviour in dairy cows (Bos taurus). If animals frequently display stereotypic behaviours, this is an indication of poor welfare. It has been suggested that animals express stereotypic behaviours as a way of coping with stress. As a result, animals with stereotypic behaviours may have lower levels of stress hormones than animals without stereotypic behaviours. In this study, 916 Holstein cows in the first lactation were subjected to scan sampling behavioural observations 200 times for 10 days. All cows were assigned to either a stereotypic behaviours group (SB) or a control group (CON). The SB group was further subdivided into a tongue-rolling group (TR) and an other-stereotypic behaviours group (OS). The TR group was also split into an only tongue-rolling group (OTR) and a mixed tongue-rolling and other stereotypic behaviours group (TROS). Some cows in the TR group belonged to an extreme tongue-rolling group (ETR). Hair and saliva samples were collected from 601 cows to test cortisol concentrations and dairy herd improvement (DHI) data were collected from a total of 762 cows. There were no differences in hair or saliva cortisol concentrations between the groups (p>0.05), and the frequencies of tongue-rolling were not associated with cortisol concentrations (p>0.05). For DHI in cows, the milk protein percentage (p = 0.028), milk true protein percentage (p = 0.021) and milk crude protein percentage (p = 0.023) of cows in the ETR group were significantly lower than those in the CON group. For cows in ETR group, as the frequencies of tongue-rolling increased, the milk protein percentage (p = 0.034, r = 0.365), milk true protein percentage (p = 0.022, r = 0.393) and milk crude protein percentage (p = 0.035, r = 0.363) increased. We investigated the relationship between stereotypic behaviours and stress by using a non-invasive sampling method to minimise harm to the cows. We suggest that tongue-rolling may not be a way for cows to cope with stress, at least in terms of cortisol concentrations.

Administration of Atosiban, an oxytocin receptor antagonist, ameliorates autistic-like behaviors in a female rat model of valproic acid-induced autism

Autism spectrum disorder (ASD) is a pervasive developmental disorder with gender differences. Oxytocin (OXT) is currently an important candidate drug for autism, but the lack of data on female autism is a big issue. It has been reported that the effect of OXT is likely to be different between male and female ASD patients. In the study, we specifically explored the role of the OXT signaling pathway in a VPA-induced female rat’s model of autism. The data showed that there was an increase of either oxytocin or its receptor expressions in both the hippocampus and the prefrontal cortex of VPA-induced female offspring. To determine if the excess of OXT signaling contributed to autism symptoms in female rats, exogenous oxytocin and oxytocin receptor antagonists Atosiban were used in the experiment. It was found that exogenous oxytocin triggered autism-like behaviors in wild-type female rats by intranasal administration. More interestingly, several autism-like deficits including social interaction, anxiety, and repeat stereotypical sexual behavior in the VPA female offspring were significantly attenuated by oxytocin receptor antagonists Atosiban. Moreover, Atosiban also effectively improved the synaptic plasticity impairment induced by VPA in female offspring. Our results suggest that oxytocin receptor antagonists significantly improve autistic-like behaviors in a female rat model of valproic acid-induced autism.

Inhibiting proBDNF to mature BDNF conversion leads to ASD-like phenotypes in vivo.

Autism Spectrum Disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is regulated by mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF in a diametrically opposite manner: proBDNF inhibits while mBDNF potentiates synapses. Here we generated a knock-in mouse line (BDNFmet/leu) in which the conversion of proBDNF to mBDNF is attenuated. Biochemical experiments revealed residual mBDNF but excessive proBDNF in the brain. Similar to other ASD mouse models, the BDNFmet/leu mice showed reduced dendritic arborization, altered spines, and impaired synaptic transmission and plasticity in the hippocampus. They also exhibited ASD-like phenotypes, including stereotypical behaviors and deficits in social interaction. Moreover, the plasma proBDNF/mBDNF ratio was significantly increased in ASD patients compared to normal children in a case-control study. Thus, deficits in proBDNF to mBDNF conversion in the brain may contribute to ASD-like behaviors, and plasma proBDNF/mBDNF ratio may be a potential biomarker for ASD.

Prenatal 1-Nitropyrene Exposure Causes Autism-Like Behavior Partially by Altering DNA Hydroxymethylation in Developing Brain.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1-nitropyrene (1-NP), a key component of motor vehicle exhaust, on autism-like behaviors in a mouse model. Three-chamber test finds that prenatal 1-NP exposure causes autism-like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1-NP-exposed weaning pups. Immunofluorescence finds that prenatal 1-NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1-NP exposure retards tangential migration of GAD67-positive interneurons and downregulates interneuron migration-related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1-NP exposure reduces hydroxymethylation of interneuron migration-related genes through inhibiting ten-eleven translocation (TET) activity in fetal forebrain. Supplement with alpha-ketoglutarate (α-KG), a cofactor of TET enzyme, reverses 1-NP-induced hypohydroxymethylation at specific sites of interneuron migration-related genes. Moreover, α-KG supplement alleviates 1-NP-induced migration retardation of interneurons in fetal forebrain. Finally, maternal α-KG supplement improves 1-NP-induced autism-like behaviors in weaning offspring. In conclusion, prenatal 1-NP exposure causes autism-like behavior partially by altering DNA hydroxymethylation of interneuron migration-related genes in developing brain.

There is more to belief than Van Leeuwen believes

Neil Van Leeuwen argues that many religious people do not act and infer as we would expect believers to act and infer, and on this basis argues that they are not genuine believers. They take some other, nondoxastic, attitude to the claims they profess to believe. In this short commentary, I argue that in many (but far from all) such cases, the content, and not the attitude, explains the departures from the inferential and behavioral stereotype we associate with belief.

Gut Microbiota in Autism Spectrum Disorder: A Systematic Review

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with stereotyped behavior and deficits in communication and social interaction. There is increasing evidence of the implication of gut microbiota in ASD. We conducted a systematic review to summarize previously published data to compare the profile of gut microbiota between autistic and neurotypical subjects. The outcomes of interventions such as prebiotics, probiotics, and microbiota transplantation therapy to overcome the symptomatology of ASD were also discussed. The current review allows us to associate gut microbiota dysbiosis and ASD. To date, there is still little consensus on which bacterial species are consistently altered in individuals with autism. Further studies are required to obtain stronger evidence of the relationship between gut microbiota and the severity of ASD conjointly with the effectiveness of dietary/probiotic interventions in reducing autistic behaviors compared to their healthy siblings.

The Association Between Gastrointestinal Issues and Psychometric Scores in Children with Autism Spectrum Disorder, Developmental Delays, Down Syndrome, and Typical Development.

Investigate the association between gastrointestinal (GI) issues and psychometric scores among children with developmental delays and typical development. We examined the association between GI issues and the Mullen Scale of Early Learning (MSEL), Vineland Adaptive Behavior Subscales (VABS), and Aberrant Behavior Checklist (ABC) scores from participants with autism spectrum disorder (ASD), Down syndrome (DS),other developmental delays (DD) and typical development (TD) from the CHildhood Autism Risk from Genetics and Environment (CHARGE) Study (n = 1603). Approximately 32% of children with ASD, 31% of children with DD, and 20% of children with DS reported at least one GI issue, compared to 7% of TD controls.Constipation was the most frequently reported symptom for the entire population, including controls. In general, GI issues correlated with poorer behavioral scores (decreased communication, daily living, socialization, and motor skills on the VABS, and increased irritability/agitation, lethargy/social withdrawal, stereotypic behavior, and hyperactivity/noncompliance on the ABC) among ASD cases. Analysis by sex indicated that GI issues also correlated with poorer cognitive scores (fine motor, receptive language, expressive language, and MSEL composite scores), and adaptive behavior (communication skills, daily living skills, motor, and VABS composite scores) among boys with DD, but not girls with DD-suggesting sex differences among DD cases. Even TD controls showed increased stereotypic behavior and social withdrawal in association with GI issues. However, GI issues were not correlated with impairments in psychometric scores among DS cases. Given that GI issues correlate with deficits in behavioral and cognitive scores, future studies should investigate the treatment of GI symptoms in children with ASD and DD.

Evaluation of the protective effect of capric acid on behavioral and biochemical alterations in valproic acid-induced model of autism

Aim and objectiveThe purpose of the study is to determine the neuroprotective effect of capric acid on sodium valproate-induced model of autism. MethodsIn this study, the effect of CA was observed in animals with single dose of valproic acid (600 mg/kg, i. p.) where the disease condition was confirmed by developmental impairment in pups. Behavioral tests that assess anxiety, depression, stereotypical and repetitive behavior, social interaction, learning and memory, and other confounding variables were performed. Subsequently, oxidative stress parameters, pro-inflammatory cytokine levels and mitochondrial complex activities in the selected brain regions were analyzed. ResultsValproic acid successfully produced autism-like symptoms from post-natal day 7 and also demonstrated impairment in social behavior, learning and memory, and anxiety and depression. Valproic acid was found to produce oxidative stress and neuro-inflammation in the hippocampus, prefrontal cortex, and cerebellum. Treatment with capric acid produced a positive effect on the alterations with maximum effects evident at 400 mg/kg, p. o. through amelioration of behavioral as well as biochemical changes. ConclusionThe current study concluded that capric acid could act as a likely candidate for the treatment and management of autism via significant modulation of neurobehavioral parameters, oxidative stress, mitochondrial dysfunction and inflammatory markers.

CHILDHOOD FEARS AS CAUSES OF STEREOTYPICAL HUMAN BEHAVIOR IN ADULTHOOD. CONTINUATION PRACTICES

Relevance. New unpredictable challenges occur every day, generating fear of terrorist attacks, energy disasters. To quickly adapt to the new realities of life, it is necessary to become as whole, psychologically stable and flexible as possible. The confessional tools for this human psyche are required. One of them is meditation. Purpose of the report: to statistically substantiate the influence of the author's meditation program on overcoming stereotypical behavior of adults caused by their childhood fears and to demonstrate the development of their psychological flexibility. Methodology. Sampl: the experimental (EG) and control (CG) groups of 34 people (21-w,13-m), (age - 21-53), who had similar socio-demographic characteristics and psychological problems Methods: Five-factor Meindfulness Questionnaire FFMQ; Scales of anxiety and worries STAI; Ambiguity Tolerance Scale MSTAT-I; New Uncertainty Tolerance Questionnaire (NTN, Kornilova T.V. ); SPB Personal Beliefs Survey; PBQ-BPD Dysfunctional Beliefs Questionnaire; K. Ryff’s Psychological Well-Being Scale; SCL-90-R Symptomatic Questionnaire; author's Child and Current Fear Scale for Adults. Results. The effectiveness of the author's program of mastering skills of decentered and impartial observation, conscious choice of cognitive and emotional reactions, abilities to "let go" and unresponsiveness has been proved. Such tools of conscious presence of program participants expanded their adaptive resources and improved psychological well-being. The regulatory effects related to the reduction of fears and anxiety occurred at the level of metacognitive functions of their consciousness.

Autism risk gene Cul3 alters neuronal morphology via caspase-3 activity in mouse hippocampal neurons.

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders (NDDs) in which children display differences in social interaction/communication and repetitive stereotyped behaviors along with variable associated features. Cul3, a gene linked to ASD, encodes CUL3 (CULLIN-3), a protein that serves as a key component of a ubiquitin ligase complex with unclear function in neurons. Cul3 homozygous deletion in mice is embryonic lethal; thus, we examine the role of Cul3 deletion in early synapse development and neuronal morphology in hippocampal primary neuronal cultures. Homozygous deletion of Cul3 significantly decreased dendritic complexity and dendritic length, as well as axon formation. Synaptic spine density significantly increased, mainly in thin and stubby spines along with decreased average spine volume in Cul3 knockouts. Both heterozygous and homozygous knockout of Cul3 caused significant reductions in the density and colocalization of gephyrin/vGAT puncta, providing evidence of decreased inhibitory synapse number, while excitatory synaptic puncta vGulT1/PSD95 density remained unchanged. Based on previous studies implicating elevated caspase-3 after Cul3 deletion, we demonstrated increased caspase-3 in our neuronal cultures and decreased neuronal cell viability. We then examined the efficacy of the caspase-3 inhibitor Z-DEVD-FMK to rescue the decrease in neuronal cell viability, demonstrating reversal of the cell viability phenotype with caspase-3 inhibition. Studies have also implicated caspase-3 in neuronal morphological changes. We found that caspase-3 inhibition largely reversed the dendrite, axon, and spine morphological changes along with the inhibitory synaptic puncta changes. Overall, these data provide additional evidence that Cul3 regulates the formation or maintenance of cell morphology, GABAergic synaptic puncta, and neuronal viability in developing hippocampal neurons in culture.

Early pyridoxine administration rescues autism-like behavior in the BTBR T+tf/J autistic model

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social impairment and repetitive, stereotyped behaviors. An imbalanced oxidative stress status and neuroinflammation are involved in ASD development. In this study, we investigated the effects of pyridoxine, a form of vitamin B6 with potent anti-oxidant and anti-inflammatory features, on autism-like behavior in BTBR T + ltpr3tf/J (BTBR) mice, a model of autism. Mice received pyridoxine from postnatal days 7 to 14. Behavioral tests were conducted on 8-week-old male mice, and the inflammatory status and oxidative stress levels were also assessed in the mouse hippocampus. Postnatal pyridoxine treatment significantly improved social deficits, stereotyped behaviors, and cognitive deficits in BTBR mice. In addition, pyridoxine treatment alleviated neuroinflammation in the hippocampus manifested by reduced Iba1+ microglia and inflammatory factors, such as interleukin-1β (IL-1β), IL-6, TNF-α, and NF-κB. Further, pyridoxine-treated BTBR mice had elevated Nrf2 and HO-1 in the hippocampus. Postnatal pyridoxine administration might improve autistic-like behaviors in BTBR mice via attenuating oxidative stress and neuroinflammation in the hippocampus.

16 Effects of fiber supplementation during gestation on sow and piglet performance

Abstract Our objective was to determine the effects of fiber supplementation during gestation on sow and piglet performance. A total of 200 PIC Camborough P1+ sows were used. At breeding, sows were balanced by body weight (BW) within parity and randomly allotted to 1 of 2 dietary treatments, which consisted of 1) Control; corn-soybean meal gestation diet; and 2) Fiber; inclusion of soybean hulls in the formulation at a level to yield a dietary crude-fiber content 6%. Females were housed in individual stalls throughout the entire gestation. At d 90 of gestation, serum glucose, fecal dry matter, fecal volatile fat acids (acetate, propionate, butyrate, isovalerate, and valerate), urinary traits (color, turbidity, density, pH, and presence of nitrate or blood), and frequency of stereotypic behavior (sham chewing, teeth grinding, bar biting, and floor licking) was accessed. Perineal scoring was visually evaluated at d 105 and 110 of gestation. Farrowing traits (farrowing length, and number of piglets born alive, stillborn, and mummified fetuses) and piglet vitality (meconium presence, umbilical cord integrity, oxygenation, and heart rate) were individually monitored. Individual piglet BW was obtained within 12 h of birth and after 24 h for colostrum intake, and at weaning. Sow daily lactation feed intake was registered. Data were analyzed using generalized linear mixed models with the Glimmix procedure of SAS with sow serving as the experimental unit. There was no evidence (P > 0.10) for differences in sow BW at d1, d112 of gestation, and at weaning. Sows fed the greater fiber diet showed lower levels of post-prandial glucose (-6%; P < 0.10), darker urine (+33%; P < 0.10) with greater pH (+5%; P < 0.05), and greater levels of fecal butyrate (+62%; P < 0.05) and isovalerate (+15%; P < 0.10) at the end of gestation (d 90). Feces from sows fed the control diet were drier (P < 0.05) at d 90 of gestation. Fiber supplementation reduced the frequency of teeth grinding (-52%; P < 0.10), bar biting (-74%; P < 0.05), and floor licking (-65%; P 0.10) behaviors. There was no evidence for treatment differences (P > 0.10) for perineal scores. Piglet vitality was not affected by the treatments, except for a marginal increase in blood oxygen saturation for piglets from sows fed the greater fiber diet (+1%; P < 0.10). Treatment did not impact (P > 0.10) farrowing duration, number of total piglets born, born alive, stillborn, and mummified, nor average piglet birth weight and colostrum intake. Sows fed diet with fiber supplementation during gestation had a marginal increase in average daily feed intake during lactation (+0.50kg/d; P = 0.08), which resulted in improved piglet BW gain (P < 0.05) and weaning weights (+0.20kg; P < 0.05). In summary, providing increased level of fiber supplementation via soybean hulls to gestating diets did not impact sow reproductive performance. Beneficial effects were observed for welfare lactation feed intake, piglet BW gain and weaning weights.

Division of labor for defensive retaliation and preemption by the peripheral and central nervous systems in the nudibranch Berghia

Relatively little is known about how peripheral nervous systems (PNSs) contribute to the patterning of behavior in which their role transcends the simple execution of central motor commands or mediation of reflexes. We sought to draw inferences to this end in the aeolid nudibranch Berghia stephanieae, which generates a rapid, dramatic defense behavior, "bristling." This behavior involves the coordinated movement of cerata, dozens of venomous appendages emerging from the animal's mantle. Our investigations revealed that bristling constitutes a stereotyped but non-reflexive two-stage behavior: an initial adduction of proximate cerata to sting the offending stimulus (stage 1) followed by a coordinated radial extension of remaining cerata to create a pincushion-like defensive screen around the animal (stage 2). In decerebrated specimens, stage 1 bristling was preserved, while stage 2 bristling was replaced by slower, uncoordinated ceratal movements. We conclude from these observations that, first, the animal's PNS and central nervous system (CNS) mediate stages 1 and 2 of bristling, respectively; second, the behavior propagates through the body utilizing both peripheral- and central-origin nerve networks that support different signaling kinetics; and third, the former network inhibits the latter in the body region being stimulated. These findings extend our understanding of the PNS' computational capacity and provide insight into a neuroethological scheme in which the CNS and PNS both independently and interactively pattern different aspects of non-reflexive behavior.