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.

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.

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 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.

Excitable calcium wave propagation in the presence of localized stores

2000 ◽  
Vol 62 (6) ◽  
pp. 8420-8426 ◽  
Author(s):  
C. S. Pencea ◽  
H. G. E. Hentschel
Keyword(s):  
Wave Propagation ◽  
Calcium Wave

Cellular Bioenergetic and Metabolic Changes in Patients with Autism Spectrum Disorder

2021 ◽  
Vol 21 ◽  
Author(s):  
Maria Gevezova ◽  
Danail Minchev ◽  
Iliana Pacheva ◽  
Yordan Sbirkov ◽  
Ralitsa Yordanova ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Mononuclear Cells ◽  
Cell Metabolism ◽  
Strong Dependence ◽  
Autism Spectrum ◽  
Metabolic Changes ◽  
Spectrum Disorder ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
And Gender

Background: Although Autism Spectrum Disorder (ASD) is considered a heterogeneous neurological disease in childhood, a growing body of evidence associates it with mitochondrial dysfunction explaining the observed comorbidities. Introduction: The aim of this study is to identify variations in cellular bioenergetics and metabolism dependent on mitochondrial function in ASD patients and healthy controls using peripheral blood mononuclear cells (PBMCs). We hypothesized that PBMCs may reveal the cellular pathology and provide evidence of bioenergetic and metabolic changes accompanying the disease. Method: PBMC from children with ASD and a control group of the same age and gender were isolated. All patients underwent an in-depth clinical evaluation. A well-characterized cohort of Bulgarian children was selected. Bioenergetic and metabolic studies of isolated PBMCs were performed with a Seahorse XFp analyzer. Result: Our data show that PBMCs from patients with ASD have increased respiratory reserve capacity (by 27.5%), increased maximal respiration (by 67%) and altered adaptive response to oxidative stress induced by DMNQ. In addition, we demonstrate а strong dependence on fatty acids and impaired ability to reprogram cell metabolism. The listed characteristics are not observed in the control group. These results can contribute to a better understanding of the underlying causes of ASD, which is crucial for selecting a successful treatment. Conclusion: The current study, for the first time, provides a functional analysis of cell bioenergetics and metabolic changes in a group of Bulgarian patients with ASD. It reveals physiological abnormalities that do not allow mitochondria to adapt and meet the increased energetic requirements of the cell. The link between mitochondria and ASD is not yet fully understood, but this may lead to the discovery of new approaches for nutrition and therapy.

Assessment of 25 Hydroxy Cholecalceferol Level in Autistic Children; is there a role for it in Treatment of Autism Spectrum Disorder?

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Martina Alfred Youssef Nakhla ◽  
Eman Ahmed Zaky ◽  
Enas Samir Nabeh ◽  
Asmaa Wafeeq Abd El Aziz
Keyword(s):  
Vitamin D ◽  
Serum Vitamin ◽  
Autism Spectrum ◽  
Laboratory Evaluation ◽  
Control Group ◽  
Autistic Children ◽  
Serum Vitamin D ◽  
Group I ◽  
Egyptian Children ◽  
Therapeutic Doses

Abstract Background Autism is a group of neurodevelopmental disabilities with various genetic and environmental risk factors. Vitamin D is an important neurosteroid hormone which can affect brain development and function, but research on its use in treating autism has been limited. Objectives The current study aimed at assessing the level of 25 OH vit D3level in a group of autistic infants and children compared to controls and correlating it with the severity of autistic manifestations and evaluation of the role of therapeutic doses of vitamin D on the severity of autistic manifestations. Methodology Thirty autistic Egyptian children (group I) and 30 clinically healthy age and sex matched controls were enrolled (group II). Therapeutic doses of vitamin D were given for autistic children who showed insufficient levels of 25 OH cholecalceferol for a period of 4-6 weeks followed by maintenance doses for another 6 weeks. Psychometric and laboratory evaluation for this group was done thrice: at the onset of study, at 6 week after enrollment in the study, and at 12 weeks after that enrollment. Results Serum vitamin D level was substantially reduced in patients with ASD in comparison to control group, and on the other hand, 25 (OH) vitamin D level was significantly negatively correlated with ATEC score and Total CARS score. Autistic children who received vitamin D3 treatment had significant improvement of CARS and ATEC scores. Conclusion vitamin D supplementation significantly improved the outcome of enrolled autistic children. It is recommended to follow up our studied sample to check the consolidation of improvement for how long it will be needed.

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