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Autism cerebellum

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https://www.readbyqxmd.com/read/28271437/cellular-and-circuitry-bases-of-autism-lessons-learned-from-the-temporospatial-manipulation-of-autism-genes-in-the-brain
#1
REVIEW
Samuel W Hulbert, Yong-Hui Jiang
Transgenic mice carrying mutations that cause Autism Spectrum Disorders (ASDs) continue to be valuable for determining the molecular underpinnings of the disorders. Recently, researchers have taken advantage of such models combined with Cre-loxP and similar systems to manipulate gene expression over space and time. Thus, a clearer picture is starting to emerge of the cell types, circuits, brain regions, and developmental time periods underlying ASDs. ASD-causing mutations have been restricted to or rescued specifically in excitatory or inhibitory neurons, different neurotransmitter systems, and cells specific to the forebrain or cerebellum...
April 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28249166/varying-intolerance-of-gene-pathways-to-mutational-classes-explain-genetic-convergence-across-neuropsychiatric-disorders
#2
Shahar Shohat, Eyal Ben-David, Sagiv Shifman
Genetic susceptibility to intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ) often arises from mutations in the same genes, suggesting that they share common mechanisms. We studied genes with de novo mutations in the three disorders and genes implicated in SCZ by genome-wide association study (GWAS). Using biological annotations and brain gene expression, we show that mutation class explains enrichment patterns more than specific disorder. Genes with loss-of-function mutations and genes with missense mutations were associated with different pathways across disorders...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28220356/overexpression-of-line-1-retrotransposons-in-autism-brain
#3
Svitlana Shpyleva, Stepan Melnyk, Oleksandra Pavliv, Igor Pogribny, S Jill James
Long interspersed nuclear elements-1 (LINE-1 or L1) are mobile DNA sequences that are capable of duplication and insertion (retrotransposition) within the genome. Recently, retrotransposition of L1 was shown to occur within human brain leading to somatic mosaicism in hippocampus and cerebellum. Because unregulated L1 activity can promote genomic instability and mutagenesis, multiple mechanisms including epigenetic chromatin condensation have evolved to effectively repress L1 expression. Nonetheless, L1 expression has been shown to be increased in patients with Rett syndrome and schizophrenia...
February 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28151561/monoamine-oxidase-a-and-b-activities-in-the-cerebellum-and-frontal-cortex-of-children-and-young-adults-with-autism
#4
Feng Gu, Ved Chauhan, Abha Chauhan
Monoamine oxidases (MAOs) catalyze the metabolism of monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine, and are key regulators for brain function. In this study, we analyzed the activities of MAO-A and MAO-B in the cerebellum and frontal cortex from subjects with autism and age-matched control subjects. In the cerebellum, MAO-A activity in subjects with autism (aged 4-38 years) was significantly lower by 20.6% than in controls. When the subjects were divided into children (aged 4-12 years) and young adults (aged 13-38 years) subgroups, a significant decrease by 27...
February 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28150911/cerebellar-contributions-to-biological-motion-perception-in-autism-and-typical-development
#5
Allison Jack, Cara M Keifer, Kevin A Pelphrey
Growing evidence suggests that posterior cerebellar lobe contributes to social perception in healthy adults. However, they know little about how this process varies across age and with development. Using cross-sectional fMRI data, they examined cerebellar response to biological (BIO) versus scrambled (SCRAM) motion within typically developing (TD) and autism spectrum disorder (ASD) samples (age 4-30 years old), characterizing cerebellar response and BIO > SCRAM-selective effective connectivity, as well as associations with age and social ability...
April 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28102228/maternal-immune-activation-causes-behavioral-impairments-and-altered-cerebellar-cytokine-and-synaptic-protein-expression
#6
Gurudutt Pendyala, Shinnyi Chou, Yoosun Jung, Pierluca Coiro, Elizabeth Spartz, Ragunathan Padmashri, Ming Li, Anna Dunaevsky
Emerging epidemiology studies indicate that maternal immune activation (MIA) resulting from inflammatory stimuli such as viral or bacterial infections during pregnancy serves as a risk factor for multiple neurodevelopmental disorders including autism spectrum disorders and schizophrenia. Although alterations in the cortex and hippocampus of MIA offspring have been described, less evidence exists on the impact on the cerebellum. Here, we report altered expression of cytokines and chemokines in the cerebellum of MIA offspring, including increase in the neuroinflammatory cytokine TNF-α and its receptor TNFR1...
January 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28077667/the-role-of-the-cerebellum-in-high-stages-of-motor-planning-hierarchy
#7
Luca Casartelli, Alessandra Federici, Ambra Cesareo, Emilia Biffi, Giulia Valtorta, Massimo Molteni, Luca Ronconi, Renato Borgatti
Motor planning is not a monolithic process, and distinct stages of motor planning are responsible for encoding different levels of abstractness. However, how these distinct components are mapped into different neural substrates remains an open question. We studied one of these high-level motor planning components, defined as second-order motor planning, in a patient (R.G.) with an extremely rare case of cerebellar agenesis but without any other cortical malformations. Second-order motor planning dictates that when two acts have to be performed sequentially, planning of the second act can influence the execution of the first...
January 11, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28063882/mice-lacking-grip1-2-show-increased-social-interactions-and-enhanced-phosphorylation-at-glua2-s880
#8
Mei Han, Rebeca Mejias, Shu-Ling Chiu, Rebecca Rose, Abby Adamczyk, Richard Huganir, Tao Wang
Glutamate receptor interacting proteins 1 and 2 (GRIP1/2) play an important role in regulating synaptic trafficking of AMPA receptor 2/3 (GluA2/3) and synaptic strength. Gain-of-function GRIP1 mutations are implicated in social behavioral deficits in autism. To study mechanisms of Grip1/2-mediated AMPA signaling in the regulation of social behaviors, we performed social behavioral testing on neuron-specific Grip1/2-double knockout (DKO) and wild type (WT) mice that are matched for age, sex, and strain background...
March 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28060873/assessment-of-anterior-cingulate-cortex-acc-and-left-cerebellar-metabolism-in-asperger-s-syndrome-with-proton-magnetic-resonance-spectroscopy-mrs
#9
Aya Goji, Hiromichi Ito, Kenji Mori, Masafumi Harada, Sonoka Hisaoka, Yoshihiro Toda, Tatsuo Mori, Yoko Abe, Masahito Miyazaki, Shoji Kagami
PURPOSE: Proton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger's syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear...
2017: PloS One
https://www.readbyqxmd.com/read/28057268/control-of-neuronal-development-by-t-box-genes-in-the-brain
#10
A B Mihalas, R F Hevner
T-box transcription factors play key roles in the regulation of developmental processes such as cell differentiation and migration. Mammals have 17 T-box genes, of which several regulate brain development. The Tbr1 subfamily of T-box genes is particularly important in development of the cerebral cortex, olfactory bulbs (OBs), and cerebellum. This subfamily is comprised of Tbr1, Tbr2 (also known as Eomes), and Tbx21. In developing cerebral cortex, Tbr2 and Tbr1 are expressed during successive stages of differentiation in the pyramidal neuron lineage, from Tbr2+ intermediate progenitors to Tbr1+ postmitotic glutamatergic neurons...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28018285/neural-signature-of-dcd-a-critical-review-of-mri-neuroimaging-studies
#11
REVIEW
Maëlle Biotteau, Yves Chaix, Mélody Blais, Jessica Tallet, Patrice Péran, Jean-Michel Albaret
The most common neurodevelopmental disorders (e.g., developmental dyslexia (DD), autism, attention-deficit hyperactivity disorder (ADHD)) have been the subject of numerous neuroimaging studies, leading to certain brain regions being identified as neural correlates of these conditions, referring to a neural signature of disorders. Developmental coordination disorder (DCD), however, remains one of the least understood and studied neurodevelopmental disorders. Given the acknowledged link between motor difficulties and brain features, it is surprising that so few research studies have systematically explored the brains of children with DCD...
2016: Frontiers in Neurology
https://www.readbyqxmd.com/read/27977875/developmental-changes-in-neuromagnetic-rhythms-and-network-synchrony-in-autism
#12
Vasily A Vakorin, Sam M Doesburg, Rachel C Leung, Vanessa M Vogan, Evdokia Anagnostou, Margot J Taylor
OBJECTIVE: There is gathering consensus that altered connectivity is a hallmark of the autistic brain. This includes atypical neural oscillations and their coordination across brain regions, which are understood to mediate information processing and integration. It remains unclear whether and how connectivity in various neurophysiological frequency ranges develops atypically in autism spectrum disorder (ASD). METHODS: To address this in a cross-sectional sample, we recorded resting-state magnetoencephalography from 134 children and adolescents with and without ASD, and calculated resting spectral power and inter-regional synchrony (functional connectivity)...
February 2017: Annals of Neurology
https://www.readbyqxmd.com/read/27957319/blood-brain-barrier-and-intestinal-epithelial-barrier-alterations-in-autism-spectrum-disorders
#13
Maria Fiorentino, Anna Sapone, Stefania Senger, Stephanie S Camhi, Sarah M Kadzielski, Timothy M Buie, Deanna L Kelly, Nicola Cascella, Alessio Fasano
BACKGROUND: Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders...
2016: Molecular Autism
https://www.readbyqxmd.com/read/27903723/cerebellar-shank2-regulates-excitatory-synapse-density-motor-coordination-and-specific-repetitive-and-anxiety-like-behaviors
#14
Seungmin Ha, Dongwon Lee, Yi Sul Cho, Changuk Chung, Ye-Eun Yoo, Jihye Kim, Jiseok Lee, Woohyun Kim, Hyosang Kim, Yong Chul Bae, Keiko Tanaka-Yamamoto, Eunjoon Kim
Shank2 is a multidomain scaffolding protein implicated in the structural and functional coordination of multiprotein complexes at excitatory postsynaptic sites as well as in psychiatric disorders, including autism spectrum disorders. While Shank2 is strongly expressed in the cerebellum, whether Shank2 regulates cerebellar excitatory synapses, or contributes to the behavioral abnormalities observed in Shank2(-/-) mice, remains unexplored. Here we show that Shank2(-/-) mice show reduced excitatory synapse density in cerebellar Purkinje cells in association with reduced levels of excitatory postsynaptic proteins, including GluD2 and PSD-93, and impaired motor coordination in the Erasmus test...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27878518/comparative-efficacy-of-alpha-linolenic-acid-and-gamma-linolenic-acid-to-attenuate-valproic-acid-induced-autism-like-features
#15
Sneha Yadav, Virendra Tiwari, Manjari Singh, Rajnish K Yadav, Subhadeep Roy, Uma Devi, Swetlana Gautam, Jitendra Kumar Rawat, Mohd Nazam Ansari, Abdulaziz Sa Saeedan, Anand Prakash, Shubhini A Saraf, Gaurav Kaithwas
The present study was undertaken to elucidate the effect of alpha-linolenic acid (ALA, 18:3, ω-3) and gamma-linolenic acid (GLA, 18:3, ω-6) on experimental autism features induced by early prenatal exposure to valproic acid (VPA) in albino wistar pups. The pups were scrutinized on the accounts of behavioral, biochemical, and inflammatory markers, and the results suggested that the GLA can impart significant protection in comparison to ALA against VPA-induced autism features. When scrutinized histopathologically, the cerebellum of the GLA-treated animals was evident for more marked protection toward neuronal degeneration and neuronal loss in comparison to ALA...
November 22, 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27876135/from-molecules-to-behavior-an-integrative-theory-of-autism-spectrum-disorder
#16
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/27871670/convergence-of-sex-differences-and-the-neuroimmune-system-in-autism-spectrum-disorder
#17
REVIEW
Margaret M McCarthy, Christopher L Wright
The male bias in autism spectrum disorder incidence is among the most extreme of all neuropsychiatric disorders, yet the origins of the sex difference remain obscure. Developmentally, males are exposed to high levels of testosterone and its byproduct, estradiol. Together these steroids modify the course of brain development by altering neurogenesis, cell death, migration, differentiation, dendritic and axonal growth, synaptogenesis, and synaptic pruning, all of which can be deleteriously impacted during the course of developmental neuropsychiatric disorders...
March 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/27868392/cerebellar-gray-matter-differentiates-children-with-early-language-delay-in-autism
#18
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
#19
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...
December 2016: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/27859903/corticostriatal-connectivity-fingerprints-probability-maps-based-on-resting-state-functional-connectivity
#20
Ellen Jaspers, Joshua H Balsters, Pegah Kassraian Fard, Dante Mantini, Nicole Wenderoth
Over the last decade, structure-function relationships have begun to encompass networks of brain areas rather than individual structures. For example, corticostriatal circuits have been associated with sensorimotor, limbic, and cognitive information processing, and damage to these circuits has been shown to produce unique behavioral outcomes in Autism, Parkinson's Disease, Schizophrenia and healthy ageing. However, it remains an open question how abnormal or absent connectivity can be detected at the individual level...
November 12, 2016: Human Brain Mapping
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