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https://www.readbyqxmd.com/read/27903723/cerebellar-shank2-regulates-excitatory-synapse-density-motor-coordination-and-specific-repetitive-and-anxiety-like-behaviors
#1
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
#2
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
#3
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
#4
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...
October 11, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27868392/cerebellar-gray-matter-differentiates-children-with-early-language-delay-in-autism
#5
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
#6
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/27859903/corticostriatal-connectivity-fingerprints-probability-maps-based-on-resting-state-functional-connectivity
#7
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
https://www.readbyqxmd.com/read/27857688/modulation-plasticity-and-pathophysiology-of-the-parallel-fiber-purkinje-cell-synapse
#8
REVIEW
Eriola Hoxha, Filippo Tempia, Pellegrino Lippiello, Maria Concetta Miniaci
The parallel fiber-Purkinje cell (PF-PC) synapse represents the point of maximal signal divergence in the cerebellar cortex with an estimated number of about 60 billion synaptic contacts in the rat and 100,000 billions in humans. At the same time, the Purkinje cell dendritic tree is a site of remarkable convergence of more than 100,000 parallel fiber synapses. Parallel fiber activity generates fast postsynaptic currents via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and slower signals, mediated by mGlu1 receptors, resulting in Purkinje cell depolarization accompanied by sharp calcium elevation within dendritic regions...
2016: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/27791298/glucocorticoid-effects-on-cerebellar-development-in-a-chicken-embryo-model-exploring-changes-in-pax6-and-mmp-9-after-exposure-to-dexamethasone
#9
Lars Peter Engeset Austdal, Sigrid Bjørnstad, Gro H Mathisen, Petra K Aden, Ingvild Mikkola, Ragnhild E Paulsen, Kirsten E Rakkestad
The developing cerebellum is vulnerable to effects of glucocorticoids and cerebellar dysfunction is associated with neurodevelopmental disorders, e.g. autism. Transcription factor PAX6 and matrix metalloproteinase-9 (MMP-9) are critical for normal cerebellar development and are highly expressed in migrating neurons. Alterations in MMP-9 and PAX6 are associated with altered cerebellar development. In the present paper we have characterized growth rate and development of the cortical layers, and further investigated how the levels of PAX6 and MMP-9 as well as glucocorticoid receptor (GR) and proliferating cell nuclear antigen (PCNA) change in the cerebellum during the fetal period (E12-21) in chicken, which corresponds to the human perinatal period...
October 28, 2016: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/27774573/the-role-of-micrornas-in-cerebellar-development-and-autism-spectrum-disorder-during-embryogenesis
#10
Lena Constantin
MicroRNAs (miRNAs) are a class of small non-coding RNA molecules with wide-ranging and subtle effects on protein production. Their activity during the development of the cerebellum provides a valuable exemplar of how non-coding molecules may assist the development and function of the central nervous system and drive neurodevelopmental disorders. Three distinct aspects of miRNA contribution to early cerebellar development will here be reviewed. Aspects are the establishment of the cerebellar anlage, the generation and maturation of at least two principal cell types of the developing cerebellar microcircuit, and the etiology and early progression of autism spectrum disorder...
October 24, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27746713/inter-method-discrepancies-in-brain-volume-estimation-may-drive-inconsistent-findings-in-autism
#11
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/27735078/the-effects-of-prenatal-h1n1-infection-at-e16-on-fmrp-glutamate-gaba-and-reelin-signaling-systems-in-developing-murine-cerebellum
#12
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
https://www.readbyqxmd.com/read/27683901/a-critical-period-in-purkinje-cell-development-is-mediated-by-local-estradiol-synthesis-disrupted-by-inflammation-and-has-enduring-consequences-only-for-males
#13
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
https://www.readbyqxmd.com/read/27616580/-the-cerebellum-as-a-major-player-in-motor-disturbances-related-to-autistic-syndrome-disorders
#14
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/27602061/increased-expression-of-fatty-acid-synthase-and-acetyl-coa-carboxylase-in-the-prefrontal-cortex-and-cerebellum-in-the-valproic-acid-model-of-autism
#15
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
https://www.readbyqxmd.com/read/27600838/intrinsic-functional-connectivity-in-preterm-infants-with-fetal-growth-restriction-evaluated-at-12-months-corrected-age
#16
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
https://www.readbyqxmd.com/read/27581745/dysfunctional-cerebellar-purkinje-cells-contribute-to-autism-like-behaviour-in-shank2-deficient-mice
#17
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
#18
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/27559688/the-cholinergic-system-in-the-cerebellum-from-structure-to-function
#19
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...
December 1, 2016: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/27543776/lhermitte-duclos-disease-with-neurofibrillary-tangles-in-heterotopic-cerebral-grey-matter
#20
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
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