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https://www.readbyqxmd.com/read/27876135/from-molecules-to-behavior-an-integrative-theory-of-autism-spectrum-disorder
#1
Alexandru-Ştefan Niculae, Denis Pavăl
Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders for which various theories have been proposed. Each theory brings valuable insights and has experimental evidence backing it, yet none provides an overarching explanation for each of the pathological aspects involved in ASD. Here we present an integrative theory of ASD, centered on a sequence of events spanning from the molecular to the behavioral level. We propose that an abnormality in the interplay between retinoic acid and sex hormones predisposes an individual to specific molecular malfunctions...
December 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27868392/cerebellar-gray-matter-differentiates-children-with-early-language-delay-in-autism
#2
Anila M D'Mello, Dorothea M Moore, Deana Crocetti, Stewart H Mostofsky, Catherine J Stoodley
Early language delay (ELD) is one of the earliest indicators of autism spectrum disorder (ASD), and predicts later cognitive and behavioral outcomes. We aimed to determine the neural correlates of ELD in autism, and examine the relationships between gray matter (GM), age of first word/phrase, and core ASD symptoms. We used voxel-based morphometry to examine whole-brain differences in GM in 8-13 year old children with autism (n = 13 ELD; n = 22 non-ELD) and 35 age-matched typically developing (TD) children...
November 2016: Autism Research: Official Journal of the International Society for Autism Research
https://www.readbyqxmd.com/read/27866083/neuroanatomical-differences-in-fast-and-slow-rat-strains-with-differential-vulnerability-to-kindling-and-behavioral-comorbidities
#3
Pragati Sharma, Stefanie Dedeurwaerdere, Michael A D Vandenberg, Ke Fang, Leigh A Johnston, Sandy R Shultz, Terence J O'Brien, Krista L Gilby
OBJECTIVE: The neurobiological factors underlying a predisposition towards developing epilepsy and its common behavioral comorbidities are poorly understood. FAST rats are a strain that has been selectively bred for enhanced vulnerability to kindling, while the SLOW strain has been bred to be resistant to kindling. FAST rats also exhibit behavioral traits reminiscent of those observed in neurodevelopmental disorders (autism spectrum disorder (ASD)/attention-deficit/hyperactivity disorder (ADHD)) commonly comorbid with epilepsy...
November 17, 2016: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/27746713/inter-method-discrepancies-in-brain-volume-estimation-may-drive-inconsistent-findings-in-autism
#4
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
https://www.readbyqxmd.com/read/27616580/-the-cerebellum-as-a-major-player-in-motor-disturbances-related-to-autistic-syndrome-disorders
#5
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
https://www.readbyqxmd.com/read/27581745/dysfunctional-cerebellar-purkinje-cells-contribute-to-autism-like-behaviour-in-shank2-deficient-mice
#6
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
https://www.readbyqxmd.com/read/27562096/treatment-of-autistic-spectrum-disorder-with-insulin-like-growth-factors
#7
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...
December 0: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/27503586/brain-enhancer-activities-at-the-gene-poor-5p14-1-autism-associated-locus
#8
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
https://www.readbyqxmd.com/read/27498245/a-single-low-dose-of-valproic-acid-in-late-prenatal-life-alters-postnatal-behavior-and-glutamic-acid-decarboxylase-levels-in-the-mouse
#9
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
https://www.readbyqxmd.com/read/27452274/regulation-of-tlx3-by-pax6-is-required-for-the-restricted-expression-of-chrn%C3%AE-3-in-cerebellar-granule-neuron-progenitors-during-development
#10
Thulasi Sheela Divya, Soundararajan Lalitha, Surendran Parvathy, Chandramohan Subashini, Rajendran Sanalkumar, Sivadasan Bindu Dhanesh, Vazhanthodi Abdul Rasheed, Mundackal Sivaraman Divya, Shubha Tole, Jackson James
Homeobox gene Tlx3 is known to promote glutamatergic differentiation and is expressed in post-mitotic neurons of CNS. Contrary to this here, we discovered that Tlx3 is expressed in the proliferating progenitors of the external granule layer in the cerebellum, and examined factors that regulate this expression. Using Pax6(-/-)Sey mouse model and molecular interaction studies we demonstrate Pax6 is a key activator of Tlx3 specifically in cerebellum, and induces its expression starting at embryonic day (E)15. By Postnatal day (PN)7, Tlx3 is expressed in a highly restricted manner in the cerebellar granule neurons of the posterior cerebellar lobes, where it is required for the restricted expression of nicotinic cholinergic receptor-α3 subunit (Chrnα3) and other genes involved in formation of synaptic connections and neuronal migration...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27423630/voluntary-saccades-in-attention-deficit-hyperactivity-disorder-looking-into-the-relationship-between-motor-impairment-and-autism-spectrum-disorder-symptoms
#11
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
https://www.readbyqxmd.com/read/27343825/valproic-acid-exposure-sequentially-activates-wnt-and-mtor-pathways-in-rats
#12
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
https://www.readbyqxmd.com/read/27337090/postnatal-behavioral-and-inflammatory-alterations-in-female-pups-prenatally-exposed-to-valproic-acid
#13
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
https://www.readbyqxmd.com/read/27250977/resting-state-functional-connectivity-changes-between-dentate-nucleus-and-cortical-social-brain-regions-in-autism-spectrum-disorders
#14
Giusy Olivito, Silvia Clausi, Fiorenzo Laghi, Anna Maria Tedesco, Roberto Baiocco, Chiara Mastropasqua, Marco Molinari, Mara Cercignani, Marco Bozzali, Maria Leggio
Autism spectrum disorders (ASDs) are known to be characterized by restricted and repetitive behaviors and interests and by impairments in social communication and interactions mainly including "theory of mind" (ToM) processes. The cerebellum has emerged as one of the brain regions affected by ASDs. As the cerebellum is known to influence cerebral cortex activity via cerebello-thalamo-cortical (CTC) circuits, it has been proposed that cerebello-cortical "disconnection" could in part underlie autistic symptoms...
June 1, 2016: Cerebellum
https://www.readbyqxmd.com/read/27242476/studying-autism-spectrum-disorder-with-structural-and-diffusion-magnetic-resonance-imaging-a-survey
#15
REVIEW
Marwa M T Ismail, Robert S Keynton, Mahmoud M M O Mostapha, Ahmed H ElTanboly, Manuel F Casanova, Georgy L Gimel'farb, Ayman El-Baz
Magnetic resonance imaging (MRI) modalities have emerged as powerful means that facilitate non-invasive clinical diagnostics of various diseases and abnormalities since their inception in the 1980s. Multiple MRI modalities, such as different types of the sMRI and DTI, have been employed to investigate facets of ASD in order to better understand this complex syndrome. This paper reviews recent applications of structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI), to study autism spectrum disorder (ASD)...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/27220548/vestibulo-ocular-reflex-function-in-children-with-high-functioning-autism-spectrum-disorders
#16
Tana B Carson, Bradley J Wilkes, Kunal Patel, Jill L Pineda, Ji H Ko, Karl M Newell, James W Bodfish, Michael C Schubert, Krestin Radonovich, Keith D White, Mark H Lewis
Sensorimotor processing alterations are a growing focus in the assessment and treatment of Autism Spectrum Disorders (ASD). The rotational vestibulo-ocular reflex (rVOR), which functions to maintain stable vision during head movements, is a sensorimotor system that may be useful in understanding such alterations and their underlying neurobiology. In this study, we assessed post-rotary nystagmus elicited by continuous whole body rotation among children with high-functioning ASD and typically developing children...
May 25, 2016: Autism Research: Official Journal of the International Society for Autism Research
https://www.readbyqxmd.com/read/27194227/alteration-of-functional-connectivity-in-autism-spectrum-disorder-effect-of-age-and-anatomical-distance
#17
Zhiliang Long, Xujun Duan, Dante Mantini, Huafu Chen
Autism spectrum disorder (ASD) is associated with disruption of local- and long-range functional connectivity (FC). The direction of those changes in FC (increase or decrease), however, is inconsistent across studies. Further, age-dependent changes of distance-specific FC in ASD remain unclear. In this study, we used resting-state functional magnetic resonance imaging data from sixty-four typical controls (TC) and sixty-four patients with ASD, whom we further classified into child (<11 years), adolescent (11-18 years) and adult cohorts (>18 years)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27073219/functional-connectivity-between-the-temporoparietal-cortex-and-cerebellum-in-autism-spectrum-disorder
#18
Kajsa M Igelström, Taylor W Webb, Michael S A Graziano
The neural basis of autism spectrum disorder (ASD) is not yet understood. ASD is marked by social deficits and is strongly associated with cerebellar abnormalities. We studied the organization and cerebellar connectivity of the temporoparietal junction (TPJ), an area that plays a crucial role in social cognition. We applied localized independent component analysis to resting-state fMRI data from autistic and neurotypical adolescents to yield an unbiased parcellation of the bilateral TPJ into 11 independent components (ICs)...
April 12, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27051288/a-prosocial-online-game-for-social-cognition-training-in-adolescents-with-high-functioning-autism-an-fmri-study
#19
Un-Sun Chung, Doug Hyun Han, Yee Jin Shin, Perry F Renshaw
To help patients with autism spectrum disorder (ASD) improve their social skills, effective interventions and new treatment modalities are necessary. We hypothesized that a prosocial online game would improve social cognition in ASD adolescents, as assessed using metrics of social communication, facial recognition, and emotional words. Ten ASD adolescents underwent cognitive behavior therapy (CBT) using a prosocial online game (game-CBT), and ten ASD adolescents participated in an offline-CBT. At baseline and 6 weeks later, social communication quality, correct identification of emotional words and facial emoticons, and brain activity were assessed in both groups...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27042284/brinp1-mice-exhibit-autism-like-behaviour-altered-memory-hyperactivity-and-increased-parvalbumin-positive-cortical-interneuron-density
#20
Susan R Berkowicz, Travis J Featherby, Zhengdong Qu, Aminah Giousoh, Natalie A Borg, Julian I Heng, James C Whisstock, Phillip I Bird
BACKGROUND: BMP/RA-inducible neural-specific protein 1 (Brinp1) is highly conserved in vertebrates, and continuously expressed in the neocortex, hippocampus, olfactory bulb and cerebellum from mid-embryonic development through to adulthood. METHODS: Brinp1 knock-out (Brinp1(-/-)) mice were generated by Cre-recombinase-mediated removal of the third exon of Brinp1. Knock-out mice were characterised by behavioural phenotyping, immunohistochemistry and expression analysis of the developing and adult brain...
2016: Molecular Autism
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