Correction: Corrigendum: Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism

Piochon, Claire; Kloth, Alexander D.; Grasselli, Giorgio; Titley, Heather K.; Nakayama, Haruo; Hashimoto, Kouichi; Wan, Vivian; Simmons, Dana H.; Eissa, Tahra L.; Nakatani, Jin; Cherskov, Adriana; Miyazaki, Toru; Watanabe, Masahiko; Takumi, Toru; Kano, Masanobu; Wang, Samuel S.‐H.; Hansel, Christian

doi:10.1038/ncomms7014

Cited by 6 publications

(3 citation statements)

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“…In the developing CB, pruning of climbing fiber occurs after the first postnatal week; this is a process essential to the establishment of topographic wiring of PCs [75, 76]. It has been postulated that incomplete synaptic pruning is a underlying cellular mechanism for ASD [77]. Previous findings suggest that a high expression of Cdh11 may increase the synaptic density in cultured neurons [78–80].…”

Section: Discussionmentioning

confidence: 99%

Segregated expressions of autism risk genes Cdh11 and Cdh9 in autism-relevant regions of developing cerebellum

et al. 2019

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Results of recent genome-wide association studies (GWAS) and whole genome sequencing (WGS) highlighted type II cadherins as risk genes for autism spectrum disorders (ASD). To determine whether these cadherins may be linked to the morphogenesis of ASD-relevant brain regions, in situ hybridization (ISH) experiments were carried out to examine the mRNA expression profiles of two ASD-associated cadherins, Cdh9 and Cdh11, in the developing cerebellum. During the first postnatal week, both Cdh9 and Cdh11 were expressed at high levels in segregated sub-populations of Purkinje cells in the cerebellum, and the expression of both genes was declined as development proceeded. Developmental expression of Cdh11 was largely confined to dorsal lobules (lobules VI/VII) of the vermis as well as the lateral hemisphere area equivalent to the Crus I and Crus II areas in human brains, areas known to mediate high order cognitive functions in adults. Moreover, in lobules VI/VII of the vermis, Cdh9 and Cdh11 were expressed in a complementary pattern with the Cdh11-expressing areas flanked by Cdh9-expressing areas. Interestingly, the high level of Cdh11 expression in the central domain of lobules VI/VII was correlated with a low level of expression of the Purkinje cell marker calbindin, coinciding with a delayed maturation of Purkinje cells in the same area. These findings suggest that these two ASD-associated cadherins may exert distinct but coordinated functions to regulate the wiring of ASD-relevant circuits in the cerebellum. Electronic supplementary material The online version of this article (10.1186/s13041-019-0461-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Segregated expressions of autism risk genes Cdh11 and Cdh9 in autism-relevant regions of developing cerebellum

et al. 2019

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“…In that study, strides were increased 13% in control mice after two administrations of 30 mg/kg MPTP 12 h apart. Interestingly, two non-MPTP studies using B6129 hybrids also showed longer strides in mouse models of autism (Piochon et al , 2015) and Alzheimer’s disease (Stover et al , 2015). A systematic study would be required to determine whether strain, low absolute dose (11 mg/kg), or other factors contributed to the longer strides in the present study.…”

Section: Discussionmentioning

confidence: 99%

Targeted deletion of GD3 synthase protects against MPTP‐induced neurodegeneration

Akkhawattanangkul

Maiti

Xue

et al. 2017

Genes Brain and Behavior

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Parkinson’s disease is a debilitating neurodegenerative condition for which there is no cure. Converging evidence implicates gangliosides in the pathogenesis of several neurodegenerative diseases, suggesting a potential new class of therapeutic targets. We have shown that interventions that simultaneously increase the neuroprotective GM1 ganglioside and decrease the pro-apoptotic GD3 ganglioside—such as inhibition of GD3 synthase (GD3S) or administration of sialidase—are neuroprotective in vitro and in a number of preclinical models. In the present study we investigated the effects of GD3S deletion on parkinsonism induced by 1-Methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP was administered to GD3S−/− mice or controls using a subchronic regimen consisting of three series of low-dose injections (11 mg/kg/day x 5 days each, 3 weeks apart), and motor function was assessed after each. The typical battery of tests used to assess parkinsonism failed to detect deficits in MPTP-treated mice. More sensitive measures—such as the force-plate actimeter and treadmill gait parameters—detected subtle effects of MPTP, some of which were absent in mice lacking GD3S. In wild-type mice MPTP destroyed 53% of the tyrosine-hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc) and reduced striatal dopamine 60.7%. In contrast, lesion size was only 22.5% in GD3S−/− mice and striatal dopamine was reduced by 37.2%. Stereological counts of Nissl-positive SNc neurons that did not express TH suggest that neuroprotection was complete but TH expression was suppressed in some cells. These results demonstrate that inhibition of GD3S has neuroprotective properties in the MPTP model may warrant further investigation as a therapeutic target.

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“…Also, mice as mammals are genetically and biologically similar to humans, however, their rapid reproduction and accelerated development allow for the testing of large numbers of animals at a relatively low cost (Hulbert and Jiang, 2016 ). Accordingly, animal models for genes of a syndromic disorder were commonly found to present autistic traits including Fragile X (FMR1) with social interaction deficits, hyperactivity, and cognitive impairments (Willem Verhoeven, 2011 ; Bhattacharya et al, 2012 ; Ronesi et al, 2012 ; Hulbert and Jiang, 2016 ; Hu et al, 2017 ), Rett syndrome and MECP2 mutations with the resulted repetitive and stereotypic/restricted behaviors, abnormal gait and reduced anxiety, decreased pain and normal olfactory discrimination (Chao et al, 2010 ; Samaco et al, 2013 ), tuberous sclerosis TSC1 or TSC2 with social interactions deficits and repetitive/restricted behavior or interest (Chao et al, 2010 ; Willem Verhoeven, 2011 ), Timothy syndrome (TS) CACNA1C with impairments in social interactions, repetitive/stereotypic behaviors, and increased fear conditioning (Ergaz et al, 2016 ), Phelan-McDermid syndrome with restricted interest as well as cognitive and motor deficits (Giza et al, 2010 ; Ergaz et al, 2016 ), PTEN mutations, cortical dysplasia focal epilepsy with deficits in regard to social interactions, restricted interest, sensory sensitivity, elevated anxiety, and seizures (Scott-Van Zeeland et al, 2010 ) (Cook and Scherer, 2008 ; LaSalle et al, 2015 ; Piochon et al, 2015 ) as behavioral features of the above described syndromes which are associated with the ASD (Table 3 ). Numerous inbred mouse strains show face validity as ASD models in addition to the genetically modified animal models of ASD, as such inbred strains display robust and well-replicated social deficits and repetitive behaviors (Kazdoba et al, 2016 ).…”

Section: Animal Models Of Asdmentioning

confidence: 99%

Current Enlightenment About Etiology and Pharmacological Treatment of Autism Spectrum Disorder

et al. 2018

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Autistic Spectrum Disorder (ASD) is a complex neurodevelopmental brain disorder characterized by two core behavioral symptoms, namely impairments in social communication and restricted/repetitive behavior. The molecular mechanisms underlying ASD are not well understood. Recent genetic as well as non-genetic animal models contributed significantly in understanding the pathophysiology of ASD, as they establish autism-like behavior in mice and rats. Among the genetic causes, several chromosomal mutations including duplications or deletions could be possible causative factors of ASD. In addition, the biochemical basis suggests that several brain neurotransmitters, e.g., dopamine (DA), serotonin (5-HT), gamma-amino butyric acid (GABA), acetylcholine (ACh), glutamate (Glu) and histamine (HA) participate in the onset and progression of ASD. Despite of convincible understanding, risperidone and aripiprazole are the only two drugs available clinically for improving behavioral symptoms of ASD following approval by Food and Drug Administration (FDA). Till date, up to our knowledge there is no other drug approved for clinical usage specifically for ASD symptoms. However, many novel drug candidates and classes of compounds are underway for ASD at different phases of preclinical and clinical drug development. In this review, the diversity of numerous aetiological factors and the alterations in variety of neurotransmitter generation, release and function linked to ASD are discussed with focus on drugs currently used to manage neuropsychiatric symptoms related to ASD. The review also highlights the clinical development of drugs with emphasis on their pharmacological targets aiming at improving core symptoms in ASD.

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Correction: Corrigendum: Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism

Cited by 6 publications

References 0 publications

Segregated expressions of autism risk genes Cdh11 and Cdh9 in autism-relevant regions of developing cerebellum

Segregated expressions of autism risk genes Cdh11 and Cdh9 in autism-relevant regions of developing cerebellum

Targeted deletion of GD3 synthase protects against MPTP‐induced neurodegeneration

Current Enlightenment About Etiology and Pharmacological Treatment of Autism Spectrum Disorder

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