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MSystems Jan 2024Probiotics can effectively improve a variety of neurological diseases, but there is little research on autism, and the specific mechanism is unclear. In this study,...
Probiotics can effectively improve a variety of neurological diseases, but there is little research on autism, and the specific mechanism is unclear. In this study, shotgun metagenomics analysis was used to investigate the preventive and therapeutic effects of subsp. Probio-M8 on autism. The results showed that Probio-M8 treatment significantly alleviated valproate (VPA)-induced autism in mice, with autistic symptoms characterized by increased stereotyped behaviors such as grooming, reduced learning ability, and decreased desire to socialize. Further studies have found that Probio-M8 can alleviate autism by optimizing gut microbiota diversity and regulating metabolic levels. Probio-M8 regulates gut microbiota structure by increasing the abundance of beneficial bacteria such as and . In addition, Probio-M8 regulates metabolic activity by increasing levels of choline, which corrects CAZy disorders. In conclusion, Probio-M8 is therapeutic in the VPA-induced autism mouse model by regulating the gut microbiome and metabolic levels.IMPORTANCEIndividuals with autism often exhibit symptoms of social invariance, obsessive-compulsive tendencies, and repetitive behaviors. However, early intervention and treatment can be effective in improving social skills and mitigating autism symptoms, including behaviors related to irritability. Although taking medication for autism may lead to side effects such as weight gain, probiotics can be an ideal intervention for alleviating these symptoms. In this study, we investigated the effects of Probio-M8 intervention on the behavior of autistic mice using an open-field test, a three-chamber sociability test, and a novel object recognition test. Metagenomic analysis revealed differences in gut microbiota diversity among groups, predicted changes in metabolite levels, and functionally annotated CAZy. Additionally, we analyzed serum neurotransmitter levels and found that probiotics were beneficial in mitigating neurotransmitter imbalances in mice with autism.
Topics: Mice; Animals; Bifidobacterium animalis; Autistic Disorder; Gastrointestinal Microbiome; Weight Gain; Neurotransmitter Agents
PubMed: 38108654
DOI: 10.1128/msystems.01013-23 -
BioRxiv : the Preprint Server For... May 2024The gustatory cortex (GC) plays a pivotal role in taste perception, with neural ensemble responses reflecting taste quality and influencing behavior. Recent work,...
The gustatory cortex (GC) plays a pivotal role in taste perception, with neural ensemble responses reflecting taste quality and influencing behavior. Recent work, however, has shown that GC taste responses change across sessions of novel taste exposure in taste-naïve rats. Here, we use single-trial analyses to explore changes in the cortical taste-code on the scale of individual trials. Contrary to the traditional view of taste perception as innate, our findings suggest rapid, experience-dependent changes in GC responses during initial taste exposure trials. Specifically, we find that early responses to novel taste are less "stereotyped" and encode taste identity less reliably compared to later responses. These changes underscore the dynamic nature of sensory processing and provides novel insights into the real-time dynamics of sensory processing across novel-taste familiarization.
PubMed: 38766243
DOI: 10.1101/2024.05.08.593234 -
BioRxiv : the Preprint Server For... Feb 2024Extrastriatal visual cortex is known to exhibit distinct response profiles to complex stimuli of varying ecological importance (e.g., faces, scenes, and tools). The...
Extrastriatal visual cortex is known to exhibit distinct response profiles to complex stimuli of varying ecological importance (e.g., faces, scenes, and tools). The dominant interpretation of these effects is that they reflect activation of distinct "category-selective" brain regions specialized to represent these and other stimulus categories. We sought to explore an alternative perspective: that the response to these stimuli is determined less by whether they form distinct categories, and more by their relevance to different forms of natural behavior. In this regard, food is an interesting test case, since it is primarily distinguished from other objects by its edibility, not its appearance, and there is evidence of food-selectivity in human visual cortex. Food is also associated with a common behavior, eating, and food consumption typically also involves the manipulation of food, often with the hands. In this context, food items share many properties in common with tools: they are graspable objects that we manipulate in self-directed and stereotyped forms of action. Thus, food items may be preferentially represented in extrastriatal visual cortex in part because of these shared affordance properties, rather than because they reflect a wholly distinct kind of category. We conducted fMRI and behavioral experiments to test this hypothesis. We found that behaviorally graspable food items and tools were judged to be similar in their action-related properties, and that the location, magnitude, and patterns of neural responses for images of graspable food items were similar in profile to the responses for tool stimuli. Our findings suggest that food-selectivity may reflect the behavioral affordances of food items rather than a distinct form of category-selectivity.
PubMed: 38529495
DOI: 10.1101/2024.02.20.581258 -
Neuropharmacology May 2024Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by deficient social communication and interaction together with restricted,...
Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by deficient social communication and interaction together with restricted, stereotyped behaviors. Currently approved treatments relieve comorbidities rather than core symptoms. Since excitation/inhibition balance and synaptic plasticity are disrupted in ASD, molecules targeting excitatory synaptic transmission appear as highly promising candidates to treat this pathology. Among glutamatergic receptors, the NMDA receptor has received particular attention through the last decade to develop novel allosteric modulators. Here, we show that positive NMDA receptor modulation by zelquistinel, a spirocyclic β-lactam platform chemical, relieves core symptoms in two genetic and one environmental mouse models of ASD. A single oral dose of zelquistinel rescued, in a dose-response manner, social deficits and stereotypic behavior in Shank3 mice while chronic intraperitoneal administration promoted a long-lasting relief of such autistic-like features in these mice. Subchronic oral mid-dose zelquistinel treatment demonstrated durable effects in Shank3, Fmr1 and in utero valproate-exposed mice. Carry-over effects were best maintained in the Fmr1 null mouse model, with social parameters being still fully recovered two weeks after treatment withdrawal. Among recently developed NMDA receptor subunit modulators, zelquistinel displays a promising therapeutic potential to relieve core symptoms in ASD patients, with oral bioavailability and long-lasting effects boding well for clinical applications. Efficacy in three mouse models with different etiologies supports high translational value. Further, this compound represents an innovative pharmacological tool to investigate plasticity mechanisms underlying behavioral deficits in animal models of ASD.
Topics: Mice; Humans; Animals; Autism Spectrum Disorder; Receptors, N-Methyl-D-Aspartate; Autistic Disorder; Stereotyped Behavior; Mice, Knockout; Disease Models, Animal; Microfilament Proteins; Nerve Tissue Proteins; Fragile X Mental Retardation Protein
PubMed: 38401792
DOI: 10.1016/j.neuropharm.2024.109889 -
Autism : the International Journal of... Aug 2023Autism spectrum disorder is a neurodevelopmental condition characterized by deficits in sociability and communication and the presence of repetitive behaviors. How...
Autism spectrum disorder is a neurodevelopmental condition characterized by deficits in sociability and communication and the presence of repetitive behaviors. How specific pathological alterations of the brain contribute to the clinical profile of autism spectrum disorder remains unknown. We previously found that a specific type of inhibitory interneuron is reduced in number in the autism spectrum disorder prefrontal cortex. Here, we assessed the relationship between interneuron reduction and autism spectrum disorder symptom severity. We collected clinical records from autism spectrum disorder ( = 20) and assessed the relationship between the severity of symptoms and interneuron number. We found that the reduced number of inhibitory interneurons that we previously reported is linked to specific symptoms of autism spectrum disorder, particularly stereotypic movements and intellectual impairments.
Topics: Humans; Autistic Disorder; Autism Spectrum Disorder; Stereotyped Behavior; Interneurons; Brain
PubMed: 36935610
DOI: 10.1177/13623613231154053 -
Brain and Behavior Sep 2023Anxious behaviors often occur in individuals who have experienced early adversity. Anxious behaviors can bring many hazards, such as social withdrawal, eating disorders,...
OBJECTIVE
Anxious behaviors often occur in individuals who have experienced early adversity. Anxious behaviors can bring many hazards, such as social withdrawal, eating disorders, negative self-efficacy, self-injurious thoughts and behaviors, anxiety disorders, and even depression. Abnormal behavior are is closely related to changes in corresponding circuit functions in the brain. This study investigated the relationship between brain circuits and anxious behaviors in maternal-deprived rhesus monkey animal model, which mimic early adversity in human.
METHODS
Twenty-five rhesus monkeys (Macaca mulatta) were grouped by two different rearing conditions: 11 normal control and mother-reared (MR) monkeys and 14 maternally deprived and peer-reared (MD) monkeys. After obtaining images of the brain areas with significant differences in maternal separation and normal control macaque function, the relationship between functional junction intensity and stereotypical behaviors was determined by correlation analysis.
RESULTS
The correlation analysis revealed that stereotypical behaviors were negatively correlated with the coupling between the left lateral amygdala subregion and the left inferior frontal gyrus in both MD and MR macaques.
CONCLUSION
This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The normalization of the regions involved in the functional connection might reverse the behavioral abnormality. It provides a solid foundation for effective intervention in human early adversity.
SIGNIFICANCE STATEMENT
This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The higher the amygdala-prefrontal connection strength, the less stereotyped behaviors exhibited by monkeys experiencing early adversity. Thus, in the future, changing the strength of the amygdala-prefrontal connection may reverse the behavioral abnormalities of individuals who experience early adversity. This study provides a solid foundation for effective intervention in humans' early adversity.
Topics: Humans; Animals; Maternal Deprivation; Anxiety; Amygdala; Frontal Lobe; Prefrontal Cortex
PubMed: 37464725
DOI: 10.1002/brb3.3027 -
BioRxiv : the Preprint Server For... Jul 2023Self-grooming behavior in rodents serves as a valuable model for investigating stereotyped and perseverative responses. Most current grooming analyses primarily rely on...
BACKGROUND
Self-grooming behavior in rodents serves as a valuable model for investigating stereotyped and perseverative responses. Most current grooming analyses primarily rely on video observation, which lacks standardization, efficiency, and quantitative information about force. To address these limitations, we developed an automated paradigm to analyze grooming using a force-plate actometer.
NEW METHOD
Grooming behavior is quantified by calculating ratios of relevant movement power spectral bands. These ratios are then input into a naïve Bayes classifier, trained with manual video observations. To validate the effectiveness of this method, we applied it to the behavioral analysis of the early-life striatal cholinergic interneuron depletion (CIN-d) mouse, a model of tic pathophysiology recently developed in our laboratory, which exhibits prolonged grooming responses to acute stressors. Behavioral monitoring was simultaneously conducted on the force-place actometer and by video recording.
RESULTS
The naïve Bayes approach achieved 93.7% accurate classification and an area under the receiver operating characteristic curve of 0.894. We confirmed that male CIN-d mice displayed significantly longer grooming durations compared to controls. However, this elevation was not correlated with increases in grooming force. Notably, haloperidol, a benchmark therapy for tic disorders, reduced both grooming force and duration.
COMPARISON WITH EXISTING METHODS
In contrast to observation-based approaches, our method affords rapid, unbiased, and automated assessment of grooming duration, frequency, and force.
CONCLUSIONS
Our novel approach enables fast and accurate automated detection of grooming behaviors. This method holds promise for high-throughput assessments of grooming stereotypies in animal models of tic disorders and other psychiatric conditions.
PubMed: 37503098
DOI: 10.1101/2023.07.08.548198 -
Heliyon Jun 2024Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit.... (Review)
Review
Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit. Transcranial magnetic stimulation (TMS) is a promising and emerging tool for the intervention of ASD by reducing both core and associate symptoms. Several reviews have been published regarding TMS-based ASD treatment, however, a systematic review on study characteristics, specific stimulating parameters, localization techniques, stimulated targets, behavioral outcomes, and neuroimage biomarker changes is lagged behind since 2018. Here, we performed a systematic search on literatures published after 2018 in PubMed, Web of Science, and Science Direct. After screening, the final systematic review included 17 articles, composing seven randomized controlled trial studies and ten open-label studies. Two studies are double-blind, while the other studies have a moderate to high risk of bias attributing to inadequate subject- and evaluator-blinding to treatment allocation. Five studies utilize theta-burst stimulation mode, and the others apply repetitive TMS with low frequency (five studies), high frequency (six studies), and combined low and high frequency stimulation (one study). Most researchers prioritize the bilateral dorsolateral prefrontal lobe as stimulation target, while parietal lobule, inferior parietal lobule, and posterior superior temporal sulci have also emerged as new targets of attention. One third of the studies use neuronavigation based on anatomical magnetic resonance imaging to locate the stimulation target. After TMS intervention, discernible enhancements across a spectrum of scales are evident in stereotyped behavior, repetitive behavior, and verbal social domains. A comprehensive review of literature spanning the last five years demonstrates the potential of TMS treatment for ASD in ameliorating the clinical core symptoms.
PubMed: 38933955
DOI: 10.1016/j.heliyon.2024.e32251 -
Journal of Traditional and... Jul 2023Experimental autism in rodents can be caused by prenatal valproic acid (VPA) exposure. Some diseases, such as attention-deficit hyperactivity disorder (ADHD), insomnia,...
Experimental autism in rodents can be caused by prenatal valproic acid (VPA) exposure. Some diseases, such as attention-deficit hyperactivity disorder (ADHD), insomnia, opiate withdrawal, and generalized anxiety disorder can be treated by consuming Passiflora incarnata, due to the possession of bioactive compounds like alkaloids, phenols, and flavonoids. The present study aims to investigate the role of the hydroalcoholic extract Passiflora incarnata in behavioral and oxidative stress aberrations induced by VPA. On the gestational day (GD), 12.5, pregnant Wistar rats received VPA (600 mg/kg subcutaneously). Male pups were treated with the extract (30,100, and 300 mg/kg) from postnatal day 35 to the end of the experiment, and underwent behavioral testing to evaluate locomotion, repetitive, and stereotyped movements, anxiety, and social and cognitive behaviors. After behavioral testing, the blood sample was taken from the left ventricle to determine serum catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (TAC). Then the animals were euthanized and their brains were taken out for histological assays of the prefrontal cortex (PFC) and CA1 hippocampus with hematoxylin/eosin. The total phenol and flavonoid content and antioxidant activity of the extract were also measured. A significant improvement was observed in behavioral disturbances, particularly with 300 mg/kg of Passiflora. Moreover, the formation of oxidative stress markers significantly decreased at this dose. The extract also reduced the percentage of damaged cells in the CA1 and PFC. The results indicated that Passiflora extract could ameliorate VPA-induced behavioral aberrations possibly due to the antioxidant actions of its bioactive compounds.
PubMed: 37396155
DOI: 10.1016/j.jtcme.2023.02.005 -
Clinical Interventions in Aging 2023Past research has shown that exposure to the image of a slim person reduces food consumption among young adults. However, it remains unknown whether this paradigm could...
PURPOSE
Past research has shown that exposure to the image of a slim person reduces food consumption among young adults. However, it remains unknown whether this paradigm could be adapted and applied to increase food intake among older adults with dementia by exposing them to the image of a higher-weight person to mitigate weight loss and malnutrition. The present study explored whether weight-related visual cues affect the amount of food consumed by older adults with dementia.
PARTICIPANTS AND METHODS
In the experiment, twenty-one elderly people with dementia living in a nursing home were visually exposed to one of four conditions (a cartoon image of a normal-weight chef, a higher-weight chef, a flower or no image) during real-life daily lunch situations over the course of four weeks, during which each condition was presented for one week.
RESULTS
Results demonstrate that participants finished their meals more frequently when they were exposed to the image of the higher-weight chef than when they were not exposed to any images.
CONCLUSION
These results suggest that exposure to a cartoon chef character representing a stereotyped social group related to body weight activates the stereotype and increases stereotype-consistent behavior in older adults with dementia. The present findings will contribute to understanding the effect of visual information on eating behavior and to designing eating environments which facilitate sufficient nutrition intake among older adults with dementia.
Topics: Aged; Humans; Cues; Eating; Feeding Behavior; Malnutrition; Dementia
PubMed: 37674531
DOI: 10.2147/CIA.S417254