scholarly journals A functional network signature in the developing cerebellum: evidence from a preclinical model of autism

2021 ◽  
Author(s):  
María Berenice Soria-Ortiz ◽  
Atáulfo Martínez Torres ◽  
Daniel Reyes-Haro
Keyword(s):  
Wave Propagation ◽  
Mean Amplitude ◽  
Autism Spectrum ◽  
Postnatal Period ◽  
Calcium Transients ◽  
Functional Network ◽  
Calcium Wave ◽  
Control Group ◽  
Preclinical Model ◽  
Social Deficits

Autism spectrum disorders (ASD) are pervasive neurodevelopmental conditions detected during childhood when delayed language onset and social deficits are observed. Children diagnosed with ASD frequently display sensorimotor deficits associated with the cerebellum, suggesting a dysfunction of synaptic circuits. Astroglia are part of the tripartite synapses and postmortem studies reported an increased expression of the glial fibrillary acidic protein (GFAP) in the cerebellum of ASD patients. Astroglia respond to neuronal activity with calcium transients that propagate to neighboring cells, resulting in a functional network response known as a calcium wave. This form of intercellular signaling is implicated in proliferation, migration, and differentiation of neural precursors. Prenatal exposure to valproate (VPA) is a preclinical model of ASD in which premature migration and excess of apoptosis occur in the internal granular layer (IGL) of the cerebellum during the early postnatal period. In this study we tested calcium wave propagation in the IGL of mice prenatally exposed to VPA. Sensorimotor and social deficits were observed and IGL depolarization evoked a calcium wave with astrocyte recruitment. The calcium wave propagation, initial cell recruitment, and mean amplitude of the calcium transients increased significantly in VPA-exposed mice compared to the control group. Astrocyte recruitment was significantly increased in the VPA model, but the mean amplitude of the calcium transients was unchanged. Western blot and histological studies revealed an increased expression of GFAP and higher astroglial density. We conclude that the functional network of the IGL is remarkably augmented in the preclinical model of autism.

scholarly journals A Functional Signature in the Developing Cerebellum: Evidence From a Preclinical Model of Autism

2021 ◽  
Vol 9 ◽  
Author(s):  
María Berenice Soria-Ortiz ◽  
Pamela Reyes-Ortega ◽  
Ataúlfo Martínez-Torres ◽  
Daniel Reyes-Haro
Keyword(s):  
Wave Propagation ◽  
Mean Amplitude ◽  
Autism Spectrum ◽  
Postnatal Period ◽  
Calcium Transients ◽  
Calcium Wave ◽  
Control Group ◽  
Preclinical Model ◽  
Intercellular Signaling ◽  
Sensorimotor Deficits

Autism spectrum disorders (ASD) are pervasive neurodevelopmental conditions detected during childhood when delayed language onset and social deficits are observed. Children diagnosed with ASD frequently display sensorimotor deficits associated with the cerebellum, suggesting a dysfunction of synaptic circuits. Astroglia are part of the tripartite synapses and postmortem studies reported an increased expression of the glial fibrillary acidic protein (GFAP) in the cerebellum of ASD patients. Astroglia respond to neuronal activity with calcium transients that propagate to neighboring cells, resulting in a functional response known as a calcium wave. This form of intercellular signaling is implicated in proliferation, migration, and differentiation of neural precursors. Prenatal exposure to valproate (VPA) is a preclinical model of ASD in which premature migration and excess of apoptosis occur in the internal granular layer (IGL) of the cerebellum during the early postnatal period. In this study we tested calcium wave propagation in the IGL of mice prenatally exposed to VPA. Sensorimotor deficits were observed and IGL depolarization evoked a calcium wave with astrocyte recruitment. The calcium wave propagation, initial cell recruitment, and mean amplitude of the calcium transients increased significantly in VPA-exposed mice compared to the control group. Astrocyte recruitment was significantly increased in the VPA model, but the mean amplitude of the calcium transients was unchanged. Western blot and histological studies revealed an increased expression of GFAP, higher astroglial density and augmented morphological complexity. We conclude that the functional signature of the IGL is remarkably augmented in the preclinical model of autism.

Comparing the Genetic Detox Ability and Heavy Metal Burden in a Cohort of Samples of Egyptian Children and those with Autistic Spectrum Disorder

2019 ◽  
Author(s):  
Blaurock-Busch E
Keyword(s):  
Heavy Metal ◽  
Autism Spectrum ◽  
Control Group ◽  
Potentially Toxic Metals ◽  
Gstt1 Null Genotype ◽  
Egyptian Children ◽  
Glutathione S Transferases ◽  
Metal Burden ◽  
Detoxification Pathway

The heavy metal burden of patients with Autism spectrum disorders (ASD) has been widely discussed [1-5]. Present knowledge suggests that ASD patients, compared to ‘normal’s’ show a greater metal burden, which may be a cause of the ASD pathogenesis, possibly due to a limited detoxification potential. We thus aimed to evaluate if the metal burden of ASD children is due to comprised detoxification ability, and if missing of enzymes such as the glutathione-S-transferases provide an explanation, or if additional factors play a role. Genetically, we noticed a slight difference in the detoxification ability of the ASD group compared to the Control group. In the ASD group, carrier of the genotype GSTT1 null genotype (i.e. the homozygous loss) are 1.7 times more common as in the Control group and the GSTT1 allele is more frequent in the ASD patient collective. These findings are not statistically significant but indicate a trend. In addition, our data indicates that levels of potentially toxic metals in blood and hair of both groups demonstrate a similar immediate and long-term exposure. However, 36% of the ASD group showed signs of zinc deficiency compared to 11% of the Control group and this points towards inefficiency of the Phase I detoxification pathway. More research is needed to explore the role of other elements in the detoxification pathway.

scholarly journals Autism Spectrum Disorder (ASD) with and without Mental Regression is Associated with Changes in the Fecal Microbiota

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 337 ◽  
Author(s):  
Julio Plaza-Díaz ◽  
Antonio Gómez-Fernández ◽  
Natalia Chueca ◽  
María Torre-Aguilar ◽  
Ángel Gil ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Present Report ◽  
Principal Component ◽  
Autism Spectrum ◽  
Control Group ◽  
Healthy Group ◽  
Sequencing Platform ◽  
Preliminary Results ◽  
Children With Asd ◽  
Mental Regression

New microbiome sequencing technologies provide novel information about the potential interactions among intestinal microorganisms and the host in some neuropathologies as autism spectrum disorders (ASD). The microbiota–gut–brain axis is an emerging aspect in the generation of autistic behaviors; evidence from animal models suggests that intestinal microbial shifts may produce changes fitting the clinical picture of autism. The aim of the present study was to evaluate the fecal metagenomic profiles in children with ASD and compare them with healthy participants. This comparison allows us to ascertain how mental regression (an important variable in ASD) could influence the intestinal microbiota profile. For this reason, a subclassification in children with ASD by mental regression (AMR) and no mental regression (ANMR) phenotype was performed. The present report was a descriptive observational study. Forty-eight children aged 2–6 years with ASD were included: 30 with ANMR and 18 with AMR. In addition, a control group of 57 normally developing children was selected and matched to the ASD group by sex and age. Fecal samples were analyzed with a metagenomic approach using a next-generation sequencing platform. Several differences between children with ASD, compared with the healthy group, were detected. Namely, Actinobacteria and Proteobacteria at phylum level, as well as, Actinobacteria, Bacilli, Erysipelotrichi, and Gammaproteobacteria at class level were found at higher proportions in children with ASD. Additionally, Proteobacteria levels showed to be augmented exclusively in AMR children. Preliminary results, using a principal component analysis, showed differential patterns in children with ASD, ANMR and AMR, compared to healthy group, both for intestinal microbiota and food patterns. In this study, we report, higher levels of Actinobacteria, Proteobacteria and Bacilli, aside from Erysipelotrichi, and Gammaproteobacteria in children with ASD compared to healthy group. Furthermore, AMR children exhibited higher levels of Proteobacteria. Further analysis using these preliminary results and mixing metagenomic and other “omic” technologies are needed in larger cohorts of children with ASD to confirm these intestinal microbiota changes.

FMS Effects of a Motor Program for Children With Autism Spectrum Disorders

2021 ◽  
pp. 003151252110100
Author(s):  
Liangshan Dong ◽  
Bo Shen ◽  
YanLi Pang ◽  
Mingting Zhang ◽  
Yuan Xiang ◽  
...  
Keyword(s):  
Motor Development ◽  
Group Versus ◽  
Motor Program ◽  
Autism Spectrum ◽  
Control Group ◽  
Gross Motor Development ◽  
Children With Asd ◽  
Individualized Approach ◽  
Experimental Group ◽  
Ball Skills

The current study evaluated the effectiveness of a motor program that specifically targeted fundamental motor skills (FMS) in children with ASD. The experimental group (n=21) participated in a 9-week program with motor instructions for 80 minutes/day, three days/week, while the control group (n=29) did not participate in the program. We measured FMS (using the Test of Gross Motor Development-3) one-week before, one-week after, and two-months after the program. Children in the experimental group had significantly larger FMS improvements than the controls on both locomotor and ball skills immediately following the program, and these participants showed continuous improvement on locomotor, but not ball skills, at 2-months follow-up. In individual analyses, 80% of children in the experimental group versus 29% of children in the control group showed continuous locomotor skills improvement beyond their pre-test levels. These findings highlight the importance of both a long-term motor development intervention and an individualized approach for evaluating improved FMS among children with ASD.

scholarly journals Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
J. Ellegood ◽  
S. P. Petkova ◽  
A. Kinman ◽  
L. R. Qiu ◽  
A. Adhikari ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Ex Vivo ◽  
Chromatin Modification ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Social Deficits ◽  
Altered Expression ◽  
Developmental Growth ◽  
And Behavior

Abstract Background One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification and the genes that regulate chromatin. AT-rich interactive domain 1B (ARID1B), a chromatin modifier, has been linked to autism spectrum disorder and to affect rare and inherited genetic variation in a broad set of NDDs. Methods A novel preclinical mouse model of Arid1b deficiency was created and validated to characterize and define neuroanatomical, behavioral and transcriptional phenotypes. Neuroanatomy was assessed ex vivo in adult animals and in vivo longitudinally from birth to adulthood. Behavioral testing was also performed throughout development and tested all aspects of motor, learning, sociability, repetitive behaviors, seizure susceptibility, and general milestones delays. Results We validated decreased Arid1b mRNA and protein in Arid1b+/− mice, with signatures of increased axonal and synaptic gene expression, decreased transcriptional regulator and RNA processing expression in adult Arid1b+/− cerebellum. During neonatal development, Arid1b+/− mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b+/− mice showed low motor skills in open field exploration and normal three-chambered approach. Arid1b+/− mice had learning and memory deficits in novel object recognition but not in visual discrimination and reversal touchscreen tasks. Social interactions in the male–female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviors were observed. Brains of adult Arid1b+/− mice had a smaller cerebellum and a larger hippocampus and corpus callosum. The corpus callosum increase seen here contrasts previous reports which highlight losses in corpus callosum volume in mice and humans. Limitations The behavior and neuroimaging analyses were done on separate cohorts of mice, which did not allow a direct correlation between the imaging and behavioral findings, and the transcriptomic analysis was exploratory, with no validation of altered expression beyond Arid1b. Conclusions This study represents a full validation and investigation of a novel model of Arid1b+/− haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs.

The Dopamine Hypothesis of Autism Spectrum Disorder Revisited: Current Status and Future Prospects

2021 ◽  
pp. 1-11
Author(s):  
Denis Pavăl ◽  
Ioana Valentina Micluția
Keyword(s):  
Autism Spectrum Disorder ◽  
Dopaminergic System ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Current Status ◽  
Social Deficits ◽  
Future Prospects ◽  
Autistic Behavior ◽  
Stereotyped Behaviors ◽  
Dopamine Hypothesis

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. Despite intensive research, its etiopathogenesis remains largely unclear. Although studies consistently reported dopaminergic anomalies, a coherent dopaminergic model of ASD was lacking until recently. In 2017, we provided a theoretical framework for a “dopamine hypothesis of ASD” which proposed that autistic behavior arises from a dysfunctional midbrain dopaminergic system. Namely, we hypothesized that malfunction of 2 critical circuits originating in the midbrain, that is, the mesocorticolimbic and nigrostriatal pathways, generates the core behavioral features of ASD. Moreover, we provided key predictions of our model along with testing means. Since then, a notable number of studies referenced our work and numerous others provided support for our model. To account for these developments, we review all these recent data and discuss their implications. Furthermore, in the light of these new insights, we further refine and reconceptualize our model, debating on the possibility that various etiologies of ASD converge upon a dysfunctional midbrain dopaminergic system. In addition, we discuss future prospects, providing new means of testing our hypothesis, as well as its limitations. Along these lines, we aimed to provide a model which, if confirmed, could provide a better understanding of the etiopathogenesis of ASD along with new therapeutic strategies.

scholarly journals Autistic traits in offspring of schizophrenic patients in comparison to those of normal population: a case-control study

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Shimaa Ibrahim Amin ◽  
Ghada Mohamed Salah EL-Deen
Keyword(s):  
Social Class ◽  
Autistic Traits ◽  
Autism Spectrum ◽  
Cutoff Point ◽  
Control Group ◽  
Case Group ◽  
Parental History ◽  
Autism Quotient ◽  
Wide Range ◽  
Schizophrenic Patients

Abstract Background Autism is not a discreet condition and those families members with autistic propend are more likely to display autistic symptoms with a wide range of severity, even below the threshold for diagnosis of autism spectrum disorders. Even with a parental history of schizophrenia, the likelihood of autistic spectrum disorder was found to be 3-fold greater. The aim of this study is to assess autistic traits among offspring of schizophrenic patients in the age group from 4 to 11 years and compare it in the offspring of normal individuals, and its association with the sociodemographic data. To determine whether schizophrenic parents are a risk factor to autistic traits in their children. Results There was a statistically significant (P < 0.05*) increase in Autism Quotient Child scores of the case group where 47.2% had a score equal or more than the cutoff point (76), while only 17 19.4% of the control group had the same score with odds = 3.71 indicating that children of schizophrenic parents 18 were three times likely to have Autism Quotient-Child score greater than or equal to the cutoff point (76) than 19 children of healthy parents. No statistically significant association (P ≥ 0.05) was found between all 20 sociodemographic characteristics and Autism Quotient-Child scores among the case group except for family 21 income and social class where there was a statistically significant association (P < 0.05) between insufficient income 22 and low social class and higher Autism Quotient-Child score (≥ 76). Conclusions Children of schizophrenic parents are at high risk to have autistic traits than children of normal parents.

Quantitative analysis of static equilibrium in women after mastectomy

2014 ◽  
Vol 14 (1) ◽  
pp. 81-87
Author(s):  
Maciej Rachwał ◽  
Justyna Drzał-Grabiec ◽  
Katarzyna Walicka-Cupryś ◽  
Aleksandra Truszczyńska
Keyword(s):  
Mean Amplitude ◽  
Control Group ◽  
Foot Pressure ◽  
Locomotor System ◽  
Center Of Foot Pressure ◽  
The Mean ◽  
Almost All ◽  
Posture Stability ◽  
Mastectomy Group ◽  
Better Than

Abstract Background: The post-mastectomy changes to the locomotor system are related to the scar and adhesion or to the lymphatic edema after amputation which, in turn, lead to local and global distraction of the work of the muscles. These changes lead to body statics disturbance that changes the projection of the center of gravity and worsens motor response due to changing of the muscle sensitivity. Objective: The aim of the study was to evaluate the static balance of women after undergoing mastectomy. Methods: The study included 150 women, including 75 who underwent mastectomy (mean age: 60±7.6) years, mean body mass index (BMI): 26 (±3.6) kg/m2) and 75 who were placed in the control group with matched age and BMI. The study was conducted using a tensometric platform. Results: Statistically significant differences were found for almost all parameters between the post-mastectomy group and group of healthy women, regarding center of foot pressure (COP) path length in the Y and X axes and the mean amplitude of COP. Conclusions: First, the findings revealed that balance in post-mastectomy women is significantly better than in the control group. Second, physiotherapeutic treatment of post-mastectomy women may have improved their posture stability compared with their peers.

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