scholarly journals Altered neocortical gene expression, brain overgrowth and functional over-connectivity in Chd8 haploinsufficient mice

2017 ◽  
Author(s):  
Philipp Suetterlin ◽  
Shaun Hurley ◽  
Conor Mohan ◽  
Kimberley L. H. Riegman ◽  
Marco Pagani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Brain Size ◽  
Brain Connectivity ◽  
Neuropsychiatric Symptoms ◽  
Autism Spectrum ◽  
Social Stimuli ◽  
Motor Delay ◽  
Behavioural Phenotypes ◽  
Spectrum Disorders

ABSTRACTTruncating CHD8 mutations are amongst the highest confidence risk factors for autism spectrum disorders (ASD) identified to date. Here, we report that Chd8 heterozygous mice display increased brain size, motor delay, hypertelorism, pronounced hypoactivity and anomalous responses to social stimuli. Whereas gene expression in the neocortex is only mildly affected at mid-gestation, over 600 genes are differentially expressed in the early postnatal neocortex. Genes involved in cell adhesion and axon guidance are particularly prominent amongst the down-regulated transcripts. Resting-state functional MRI identified increased synchronised activity in cortico-hippocampal and auditory-parietal networks in Chd8 heterozygous mutant mice, implicating altered connectivity as a potential mechanism underlying the behavioural phenotypes. Together, these data suggest that altered brain growth and diminished expression of important neurodevelopmental genes that regulate long-range brain wiring are followed by distinctive anomalies in functional brain connectivity in Chd8+/- mice. Human imaging studies have reported altered functional connectivity in ASD patients, with long-range under-connectivity seemingly more frequent. Our data suggest that CHD8 haploinsufficiency represents a specific subtype of ASD where neuropsychiatric symptoms are underpinned by long-range over-connectivity.

scholarly journals Brain Network Organization Correlates with Autistic Features in Preschoolers with Autism Spectrum Disorders and in Their Fathers: Preliminary Data from a DWI Analysis

2019 ◽  
Vol 8 (4) ◽  
pp. 487 ◽  
Author(s):  
Billeci ◽  
Calderoni ◽  
Conti ◽  
Lagomarsini ◽  
Narzisi ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Brain Connectivity ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Brain Network ◽  
Local Network ◽  
Network Organization ◽  
Frontal Pole ◽  
Structural Network ◽  
Spectrum Disorders

Autism Spectrum Disorders (ASD) is a group of neurodevelopmental disorders that is characterized by an altered brain connectivity organization. Autistic traits below the clinical threshold (i.e., the broad autism phenotype; BAP) are frequent among first-degree relatives of subjects with ASD; however, little is known regarding whether subthreshold behavioral manifestations of ASD mirror also at the neuroanatomical level in parents of ASD probands. To this aim, we applied advanced diffusion network analysis to MRI of 16 dyads consisting of a child with ASD and his father in order to investigate: (i) the correlation between structural network organization and autistic features in preschoolers with ASD (all males; age range 1.5–5.2 years); (ii) the correlation between structural network organization and BAP features in the fathers of individuals with ASD (fath-ASD). Local network measures significantly correlated with autism severity in ASD children and with BAP traits in fath-ASD, while no significant association emerged when considering the global measures of brain connectivity. Notably, an overlap of some brain regions that are crucial for social functioning (cingulum, superior temporal gyrus, inferior temporal gyrus, middle frontal gyrus, frontal pole, and amygdala) in patients with ASD and fath-ASD was detected, suggesting an intergenerational transmission of these neural substrates. Overall, the results of this study may help in elucidating the neurostructural endophenotype of ASD, paving the way for bridging connections between underlying genetic and ASD symptomatology.

scholarly journals Local and long-range functional connectivity is reduced in concert in autism spectrum disorders

2013 ◽  
Vol 110 (8) ◽  
pp. 3107-3112 ◽  
Author(s):  
S. Khan ◽  
A. Gramfort ◽  
N. R. Shetty ◽  
M. G. Kitzbichler ◽  
S. Ganesan ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Functional Connectivity ◽  
Long Range ◽  
Autism Spectrum ◽  
Spectrum Disorders

scholarly journals Abnormal Brain Connectivity Spectrum Disorders Following Thimerosal Administration

Dose-Response ◽  
2017 ◽  
Vol 15 (1) ◽  
pp. 155932581769084 ◽  
Author(s):  
David A. Geier ◽  
Janet K. Kern ◽  
Kristin G. Homme ◽  
Mark R. Geier
Keyword(s):  
Attention Deficit ◽  
Attention Deficit Disorder ◽  
Brain Connectivity ◽  
Febrile Seizures ◽  
Vaccine Safety ◽  
Autism Spectrum ◽  
Haemophilus Influenzae Type ◽  
Hyperkinetic Syndrome ◽  
Spectrum Disorders ◽  
Abnormal Brain

Background: Autism spectrum disorder (ASD), tic disorder (TD), and hyperkinetic syndrome of childhood (attention deficit disorder [ADD]/attention deficit hyperactivity disorder [ADHD]) are disorders recently defined as abnormal connectivity spectrum disorders (ACSDs) because they show a similar pattern of abnormal brain connectivity. This study examines whether these disorders are associated with exposure to thimerosal, a mercury (Hg)-based preservative. Methods: A hypothesis testing case-control study evaluated the Vaccine Safety Datalink for the potential dose-dependent odds ratios (ORs) for diagnoses of ASD, TD, and ADD/ADHD compared to controls, following exposure to Hg from thimerosal-containing Haemophilus influenzae type b vaccines administrated within the first 15 months of life. Febrile seizures, cerebral degeneration, and unspecified disorders of metabolism, which are not biologically plausibly linked to thimerosal, were examined as control outcomes. Results: On a per 25 μg Hg basis, cases diagnosed with ASD (OR = 1.493), TD (OR = 1.428), or ADD/ADHD (OR = 1.503) were significantly ( P < .001) more likely than controls to have received increased Hg exposure. Similar relationships were observed when separated by gender. Cases diagnosed with control outcomes were no more likely than controls to have received increased Hg exposure. Conclusion: The results suggest that Hg exposure from thimerosal is significantly associated with the ACSDs of ASD, TD, and ADD/ADHD.

scholarly journals Gene expression in blood is associated with risperidone response in children with autism spectrum disorders

2011 ◽  
Vol 12 (5) ◽  
pp. 368-371 ◽  
Author(s):  
L Lit ◽  
F R Sharp ◽  
K Bertoglio ◽  
B Stamova ◽  
B P Ander ◽  
...  
Keyword(s):  
Gene Expression ◽  
Autism Spectrum Disorders ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorders

scholarly journals An Autism Spectrum Disorder Adaptive Identification Based on the Elimination of Brain Connections: A Proof of Long-Range Underconnectivity

2021 ◽  
Author(s):  
Fatima zahra Benabdallah ◽  
Ahmed Drissi El Maliani ◽  
Dounia Lotfi ◽  
Rachid Jennane ◽  
Mohammed El hassouni
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Long Range ◽  
Data Exchange ◽  
Brain Connectivity ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Imaging Data ◽  
Brain Imaging Data

Abstract Autism spectrum disorder (ASD) is theoretically characterized by alterations in functional connectivity between brain regions. Many works presented approaches to determine informative patterns that help to predict autism from typical development. However, most of the proposed pipelines are not specifically designed for the autism problem, i.e they do not corroborate with autism theories about functional connectivity. In this paper, we propose a framework that takes into account the properties of local connectivity and long range under-connectivity in the autistic brain. The originality of the proposed approach is to adopt elimination as a technique in order to well emerge the autistic brain connectivity alterations, and show how they contribute to differentiate ASD from controls. Experimental results conducted on the large multi-site Autism Brain Imaging Data Exchange (ABIDE) show that our approach provides accurate prediction up to 70% and succeeds to prove the existence of deficits in the long-range connectivity in the ASD subjects brains.

scholarly journals Neuronal signature of social novelty exploration in the VTA: implication for Autism Spectrum Disorder

2018 ◽  
Author(s):  
Sebastiano Bariselli ◽  
Hanna Hörnberg ◽  
Clément Prévost-Solié ◽  
Stefano Musardo ◽  
Laetitia Hatstatt-Burkle ◽  
...  
Keyword(s):  
Social Interaction ◽  
Ampa Receptors ◽  
Behavioral Responses ◽  
Autism Spectrum ◽  
Excitatory Synapses ◽  
Social Stimuli ◽  
Aberrant Expression ◽  
Behavioral Deficits ◽  
Risk Gene ◽  
Spectrum Disorders

AbstractNovel stimuli attract our attention, promote exploratory behavior, and facilitate learning. Atypical habituation and aberrant novelty exploration have been related with the severity of Autism Spectrum Disorders (ASD) but the underlying neuronal circuits are unknown. Here, we report that dopamine (DA) neurons of the ventral tegmental area (VTA) promote the behavioral responses to novel social stimuli, support preference for social novelty, and mediate the reinforcing properties of novel social interaction. Social novelty exploration is associated with the insertion of calcium-permeable GluA2-lacking AMPA-type glutamate receptors at excitatory synapses on VTA DA neurons. These novelty-dependent synaptic adaptations only persist upon repeated exposure to social stimuli and sustain social interaction. Global or DA neuron-specific inactivation of the ASD risk gene Neuroligin3 alters both social novelty exploration and the reinforcing properties of social stimuli. These behavioral deficits are accompanied by an aberrant expression of non-canonical GluA2-lacking AMPA-receptors at excitatory synapses on VTA DA neurons and an occlusion of novelty-induced synaptic plasticity. Altogether, these findings causally link impaired novelty exploration in an ASD mouse model to VTA DA circuit dysfunction.

microRNAs in Autism Spectrum Disorders

2020 ◽  
Vol 25 (41) ◽  
pp. 4368-4378 ◽  
Author(s):  
Mahesh Mundalil Vasu ◽  
Puthiripadath S. Sumitha ◽  
Parakkal Rahna ◽  
Ismail Thanseem ◽  
Ayyappan Anitha
Keyword(s):  
Gene Expression ◽  
Autism Spectrum Disorders ◽  
Current Knowledge ◽  
Autism Spectrum ◽  
Mammalian Brain ◽  
Regulate Gene Expression ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Spectrum Disorders ◽  
Long Non Coding Rna

Background: Efforts to unravel the extensive impact of the non-coding elements of the human genome on cell homeostasis and pathological processes have gained momentum over the last couple of decades. miRNAs refer to short, often 18-25 nucleotides long, non-coding RNA molecules which can regulate gene expression. Each miRNA can regulate several mRNAs. Methods: This article reviews the literature on the roles of miRNAs in autism. Results: Considering the fact that ~ 1% of the human DNA encodes different families of miRNAs, their overall impact as critical regulators of gene expression in the mammalian brain should be immense. Though the autism spectrum disorders (ASDs) are predominantly genetic in nature and several candidate genes are already identified, the highly heterogeneous and multifactorial nature of the disorder makes it difficult to identify common genetic risk factors. Several studies have suggested that the environmental factors may interact with the genetic factors to increase the risk. miRNAs could possibly be one of those factors which explain this link between genetics and the environment. Conclusion: In the present review, we have summarized our current knowledge on miRNAs and their complex roles in ASD, and also on their therapeutic applications.

Sign in / Sign up

Export Citation Format

Share Document