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Autism cerebellum

Gajendra J Katuwal, Stefi A Baum, Nathan D Cahill, Chase C Dougherty, Eli Evans, David W Evans, Gregory J Moore, Andrew M Michael
Previous studies applying automatic preprocessing methods on Structural Magnetic Resonance Imaging (sMRI) report inconsistent neuroanatomical abnormalities in Autism Spectrum Disorder (ASD). In this study we investigate inter-method differences as a possible cause behind these inconsistent findings. In particular, we focus on the estimation of the following brain volumes: gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), and total intra cranial volume (TIV). T1-weighted sMRIs of 417 ASD subjects and 459 typically developing controls (TDC) from the ABIDE dataset were estimated using three popular preprocessing methods: SPM, FSL, and FreeSurfer (FS)...
2016: Frontiers in Neuroscience
S Hossein Fatemi, Timothy D Folsom, Stephanie B Liesch, Rachel E Kneeland, Mahtab Karkhane Yousefi, Paul D Thuras
Prenatal viral infection has been identified as a potential risk factor for the development of neurodevelopmental disorders such as schizophrenia and autism. Additionally, dysfunction in gamma-aminobutyric acid, Reelin, and fragile X mental retardation protein (FMRP)-metabotropic glutamate receptor 5 signaling systems has also been demonstrated in these two disorders. In the current report, we have characterized the developmental profiles of selected markers for these systems in cerebella of mice born to pregnant mice infected with human influenza (H1N1) virus on embryonic day 16 or sham-infected controls using SDS-PAGE and Western blotting techniques and evaluated the presence of abnormalities in the above-mentioned markers during brain development...
October 13, 2016: Journal of Neuroscience Research
Jessica F Hoffman, Christopher L Wright, Margaret M McCarthy
UNLABELLED: Identifying and understanding critical periods in brain development is essential to decoding the long-term impact of widespread, poorly defined, and frequently occurring insults such as inflammation. Using the laboratory rat Rattus norvegicus, we have discovered a narrowly constrained critical period in Purkinje neuron development subject to dysregulation by inflammation. The onset and offset of heightened vulnerability are attributed to a tightly orchestrated gene expression profile present only during the second postnatal week and not the first or third weeks...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
M Jaber
SCIENTIFIC BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental disorders associated with disturbances in communication, social interactions, cognition and affect. ASD are also accompanied by complex movement disorders, including ataxia. A special focus of recent research in this area is made on the striatum and the cerebellum, two structures known not only to control movement but also to be involved in cognitive functions such as memory and language. Dysfunction within the motor system may be associated with abnormal movements in ASD that are translated into ataxia, abnormal pattern of righting, gait sequencing, development of walking, and hand positioning...
September 8, 2016: L'Encéphale
Jianling Chen, Wei Wu, Yingmei Fu, Shunying Yu, Donghong Cui, Min Zhao, Yasong Du, Jijun Li, Xiaohong Li
The primary aim of the present study was to investigate alterations in enzymes associated with fatty acid synthesis, namely fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC), in the prefrontal cortex and cerebellum of the valproic acid (VPA)-induced animal model of autism. In this model, pregnant rats were given a single intraperitoneal injection of VPA, and prefrontal cortex and cerebellum samples from their pups were analyzed. The results of western blotting and reverse transcription-quantitative polymerase chain reaction analyses demonstrated that the protein and mRNA expression levels of FASN, ACC and phospho-ACC (pACC) were increased in the prefrontal cortex and cerebellum of the VPA model of autism...
September 2016: Experimental and Therapeutic Medicine
Nelly Padilla, Peter Fransson, Antonio Donaire, Francesc Figueras, Angela Arranz, Magdalena Sanz-Cortés, Violeta Tenorio, Núria Bargallo, Carme Junqué, Hugo Lagercrantz, Ulrika Ådén, Eduard Gratacós
Fetal growth restriction (FGR) affects brain development in preterm infants, but little is known about its effects on resting-state functional connectivity. We compared 20 preterm infants, born at <34 weeks of gestation with abnormal antenatal Doppler measurements and birth weights <10th percentile, with 20 appropriate for gestational age preterm infants of similar gestational age and 20 term infants. They were scanned without sedation at 12 months of age and screened for autistic traits at 26 months...
September 6, 2016: Cerebral Cortex
Saša Peter, Michiel M Ten Brinke, Jeffrey Stedehouder, Claudia M Reinelt, Bin Wu, Haibo Zhou, Kuikui Zhou, Henk-Jan Boele, Steven A Kushner, Min Goo Lee, Michael J Schmeisser, Tobias M Boeckers, Martijn Schonewille, Freek E Hoebeek, Chris I De Zeeuw
Loss-of-function mutations in the gene encoding the postsynaptic scaffolding protein SHANK2 are a highly penetrant cause of autism spectrum disorders (ASD) involving cerebellum-related motor problems. Recent studies have implicated cerebellar pathology in the aetiology of ASD. Here we evaluate the possibility that cerebellar Purkinje cells (PCs) represent a critical locus of ASD-like pathophysiology in mice lacking Shank2. Absence of Shank2 impairs both PC intrinsic plasticity and induction of long-term potentiation at the parallel fibre to PC synapse...
2016: Nature Communications
Raili Riikonen
There are no treatments for the core symptoms of autistic spectrum disorder (ASD), but there is now more knowledge on emerging mechanisms and on mechanism-based therapies. In autism there are altered synapses: genes affected are commonly related to synaptic and immune function. Dysregulation of activity-dependent signaling networks may have a key role the etiology of autism. There is an over-activation of IGF-AKT-mTor in autism spectrum disorders. Morphological and electro-physiological defects of the cerebellum are linked to system-wide ASD-like behavior defects...
November 2016: European Journal of Paediatric Neurology: EJPN
Changzheng Zhang, Peiling Zhou, Tifei Yuan
The cerebellar cholinergic system belongs to the third type of afferent nerve fiber system (after the climbing and mossy fibers), and has important modulatory effects on cerebellar circuits and cerebellar-mediated functions. In this report, we review the cerebellar cholinergic system, including cholinergic origins and innervations, acetylcholine receptor expression and distributions, cholinergic modulations of neuronal firing and synaptic plasticity, the cholinergic role in cerebellar-mediated integral functions, and cholinergic changes during development and aging...
August 25, 2016: Reviews in the Neurosciences
D Rusiecki, B Lach
Lhermitte-Duclos disease (LDD), a disorder first described by French physicians Lhermitte and Duclos in 1920 [25], is a benign, slow growing dysplastic gangliocytoma of the cerebellum, characterized by replacement of the granule cell layer by abnormal granule and Purkinje like cells. The most frequent presenting signs and symptoms are megalocephaly, increased intracranial pressure, nausea, hydrocephalus, ataxia, gait abnormalities, and intermittent headaches, all of which are attributed to the mass effect [6,11,25]...
2016: Folia Neuropathologica
Yukiko U Inoue, Takayoshi Inoue
Due to the vast clinical and genetic heterogeneity, identification of causal genetic determinants for autism spectrum disorder (ASD) has proven to be complex. Whereas several dozen 'rare' genetic variants for ASD susceptibility have been identified, studies are still underpowered to analyse 'common' variants for their subtle effects. A recent application of genome-wide association studies (GWAS) to ASD indicated significant associations with the single nucleotide polymorphisms (SNPs) on chromosome 5p14.1, located in a non-coding region between cadherin10 (CDH10) and cadherin9 (CDH9)...
2016: Scientific Reports
Ran Wei, Qi Li, Sylvia Lam, Jana Leung, Charlton Cheung, Xiaofan Zhang, Pak Chung Sham, Siew Eng Chua, Grainne Mary McAlonan
RATIONALE: Rodents exposed to valproic acid (VPA) in prenatal life exhibit post-natal characteristics analogous to autism spectrum disorder (ASD). Many previous studies used relatively high doses of VPA during early pregnancy, potentially confounding interpretation because the offspring are the 'survivors' of a toxic insult. Low dose or late gestation exposure has not been widely studied. OBJECTIVES: We examined the behavioral sequelae of late gestation exposure to low dose VPA in the mouse...
November 1, 2016: Behavioural Brain Research
Amanda J Connolly, Nicole J Rinehart, Beth Johnson, Nicole Papadopoulos, Joanne Fielding
Although there is little overlap in core diagnostic criteria for ADHD and Autism Spectrum Disorder (ASD), ASD symptoms are estimated to co-occur in children with ADHD in 20-50% of cases. As motor control deficits are common to both disorders, we investigated the impact of ASD symptoms on ocular motor control in children with Attention Deficit Hyperactivity Disorder-Combined Type (ADHD-CT), using a cued saccade paradigm sensitive to cerebellar ocular motor impairment in ASD. Basic saccade metrics (latency, velocity and accuracy), trial-to-trial variability, and main sequences relationships (saccade velocity for a given amplitude) were assessed, for 14 males with ADHD-CT and 14 typically developing (TD) males (aged 8-14, IQ>80)...
July 14, 2016: Neuroscience
Miguel Perez-Pouchoulen, Marta Miquel, Paul Saft, Brenda Brug, Rebeca Toledo, Maria Elena Hernandez, Jorge Manzo
Valproic acid (VPA) is an anti-epileptic drug with teratogenicity activity that has been related to autism. In rodents, exposure to VPA in utero leads to brain abnormalities similar than those reported in the autistic brain. Particularly, VPA reduces the number of Purkinje neurons in the rat cerebellum parallel to cerebellar abnormalities found in autism. Thus, we injected pregnant females on embryonic day 12 either with VPA (600mg/kg, i.p.) or 0.9% saline solution and obtained the cerebellum from their offspring at different postnatal time points...
October 2016: International Journal of Developmental Neuroscience
Brian R Mullen, Brennan Ross, Joan Wang Chou, Rana Khankan, Elvira Khialeeva, Kimberly Bui, Ellen M Carpenter
Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and major depressive disorders. Prior studies from our laboratory and others have demonstrated that the combinatorial effect of two factors-reduced expression of reelin protein and prenatal exposure to the organophosphate pesticide chlorpyrifos oxon-gives rise to acute biochemical effects and to morphological and behavioral phenotypes in adolescent and young adult mice...
June 2016: ASN Neuro
Matthew P G Allin
There is increasing evidence that points to the central role of the cerebellum in many areas of human behaviour - in health and in illness. The findings reviewed here shed further light on the developmental vulnerability of cerebellar cell types, and highlight the new imaging techniques being used in this research. This article reviews some new advances in our understanding of the normal cerebellar growth trajectory, and how this may become disturbed by pathological processes. Cerebellar development is now being implicated in many conditions, from autism and other neuropsychiatric disorders to diabetes...
October 2016: Seminars in Fetal & Neonatal Medicine
Lucia Olexová, Peter Štefánik, Lucia Kršková
Anxiety is one of the associated symptoms of autism spectrum disorder. According to the literature, increases in anxiety are accompanied by GABAergic system deregulation. The aim of our study, performed using an animal model of autism in the form of rats prenatally treated with valproic acid (VPA rats), was to investigate changes in anxiety-like behaviour and the gene expression of molecules that control levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain. Anxiety-like behaviours were investigated using zone preferences in the open field test...
August 26, 2016: Neuroscience Letters
Liyan Qin, Xufang Dai, Yunhou Yin
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, limited verbal communication and repetitive behaviors. Recent studies have demonstrated that Wnt signaling and mTOR signaling play important roles in the pathogenesis of ASD. However, the relationship of these two signaling pathways in ASD remains unclear. RESULTS: We assessed this question using the valproic acid (VPA) rat model of autism. Our results demonstrated that VPA exposure activated mTOR signaling and suppressed autophagy in the prefrontal cortex, hippocampus and cerebellum of autistic model rats, characterized by enhanced phospho-mTOR and phospho-S6 and decreased Beclin1, Atg5, Atg10, LC3-II and autophagosome formation...
September 2016: Molecular and Cellular Neurosciences
Nadia Kazlauskas, Marcos Campolongo, Luciana Lucchina, Cecilia Zappala, Amaicha Mara Depino
In Autism Spectrum Disorders (ASD), a bias to a higher incidence in boys than in girls has been reported. With the aim to identify biological mechanisms acting in female animals that could underlie this bias, we used an extensively validated mouse model of ASD: the prenatal exposure to valproic acid (VPA). We found postnatal behavioral alterations in female VPA pups: a longer latency in righting reflex at postnatal day (P) 3, and a delay in the acquisition of the acoustic startle response. We also analyzed the density of glial cells in the prefrontal cortex, hippocampus and cerebellum, in VPA and control animals...
October 2016: Psychoneuroendocrinology
Stephen Sai Folmsbee, Douglas R Wilcox, Koen Tyberghein, Pieter De Bleser, Warren G Tourtellotte, Jolanda van Hengel, Frans van Roy, Cara J Gottardi
BACKGROUND: Recent genetic association studies have linked the cadherin-based adherens junction protein alpha-T-catenin (αT-cat, CTNNA3) with the development of autism. Where αT-cat is expressed in the brain, and how its loss could contribute to this disorder, are entirely unknown. METHODS: We used the αT-cat knockout mouse to examine the localization of αT-cat in the brain, and we used histology and immunofluorescence analysis to examine the neurobiological consequences of its loss...
2016: Journal of Molecular Psychiatry
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