Reduced Glutamate Release in Adult BTBR Mouse Model of Autism Spectrum Disorder

Wei, Huijie; Ma, Yuehong; Ding, Caiyun; Jin, Guo Fan; Liu, Jianrong; Chang, Qiaoqiao; Hu, Fengyun; Yu, Lap-Fai

doi:10.1007/s11064-016-2035-5

Cited by 22 publications

(20 citation statements)

References 45 publications

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“…These findings agree with the reduction of gray matter volume over time in ASD, which is associated with increased severity of symptoms [143]. The presence of more serotonin-expressing neurons in the caudal portions of the median and dorsal raphe but decreased axon terminals in the hippocampal CA1 [134], decreased adult neurogenesis in the dentate gyrus [338], upregulation of postnatal turnover of excitatory synapses in the anterior frontal cortex [172], and unaltered synaptic density and PSD thickness in the somatosensory cortex [381] are other noteworthy features when comparing BTBR to control mice.…”

Section: Lessons From Animal Modelsmentioning

confidence: 99%

Autism spectrum disorder: neuropathology and animal models

et al. 2017

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Autism spectrum disorder (ASD) has a major impact on the development and social integration of affected individuals and is the most heritable of psychiatric disorders. An increase in the incidence of ASD cases has prompted a surge in research efforts on the underlying neuropathologic processes. We present an overview of current findings in neuropathology studies of ASD using two investigational approaches, postmortem human brains and ASD animal models, and discuss the overlap, limitations and significance of each. Postmortem examination of ASD brains has revealed global changes including disorganized gray and white matter, increased number of neurons, decreased volume of neuronal soma, and increased neuropil, the last reflecting changes in densities of dendritic spines, cerebral vasculature and glia. Both cortical and non-cortical areas show region-specific abnormalities in neuronal morphology and cytoarchitectural organization, with consistent findings reported from the prefrontal cortex, fusiform gyrus, frontoinsular cortex, cingulate cortex, hippocampus, amygdala, cerebellum and brainstem. The paucity of postmortem human studies linking neuropathology to the underlying etiology has been partly addressed using animal models to explore the impact of genetic and non-genetic factors clinically relevant for the ASD phenotype. Genetically modified models include those based on well-studied monogenic ASD genes (NLGN3, NLGN4, NRXN1, CNTNAP2, SHANK3, MECP2, FMR1, TSC1/2), emerging risk genes (CHD8, SCN2A, SYNGAP1, ARID1B, GRIN2B, DSCAM, TBR1), and copy number variants (15q11-q13 deletion, 15q13.3 microdeletion, 15q11-13 duplication, 16p11.2 deletion and duplication, 22q11.2 deletion). Models of idiopathic ASD include inbred rodent strains that mimic ASD behaviors as well as models developed by environmental interventions such as prenatal exposure to sodium valproate, maternal autoantibodies and maternal immune activation. In addition to replicating some of the neuropathologic features seen in postmortem studies, a common finding in several animal models of ASD is altered density of dendritic spines, with the direction of the change depending on the specific genetic modification, age and brain region. Overall, postmortem neuropathologic studies with larger sample sizes representative of the various ASD risk genes and diverse clinical phenotypes are warranted to clarify putative etiopathogenic pathways further and to promote the emergence of clinically relevant diagnostic and therapeutic tools. In addition, as genetic alterations may render certain individuals more vulnerable to developing the pathological changes at the synapse underlying the behavioral manifestations of ASD, neuropathologic investigation using genetically modified animal models will help to improve our understanding of the disease mechanisms and enhance the development of targeted treatments.

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Section: Lessons From Animal Modelsmentioning

confidence: 99%

Autism spectrum disorder: neuropathology and animal models

et al. 2017

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“…Consonant with such an imbalance, Wei et al (2015, 2016b) reported a decreased KCl-evoked glutamate release from synaptoneurosomes in both young adult (8 weeks) and aged BTBR mice. A rescue of that phenotype was obtained by blockade of IL-6 signaling through i.c.v.…”

Section: Molecular Mechanismsmentioning

confidence: 99%

The BTBR mouse model of idiopathic autism – Current view on mechanisms

Meyza

Blanchard

2017

Neuroscience & Biobehavioral Reviews

121

109

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Autism spectrum disorder (ASD) is the most commonly diagnosed neurodevelopmental disorder, with current estimates of more than 1% of affected children across nations. The patients form a highly heterogeneous group with only the behavioral phenotype in common. The genetic heterogeneity is reflected in a plethora of animal models representing multiple mutations found in families of affected children. Despite many years of scientific effort, for the majority of cases the genetic cause remains elusive. It is therefore crucial to include well-validated models of idiopathic autism in studies searching for potential therapeutic agents. One of these models is the BTBR T+Itpr3tf/J mouse. The current review summarizes data gathered in recent research on potential molecular mechanisms responsible for the autism-like behavioral phenotype of this strain.

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“…Interdisciplinary research platforms (including non-human models) are interested in finding relevant pharmacological treatments (Shen et al, 2016; Wei et al, 2016; Zheng et al, 2016). In this regards, oxytocin (OXT) is a promising therapy.…”

Section: Introductionmentioning

confidence: 99%

Communication Impairment in Ultrasonic Vocal Repertoire during the Suckling Period of Cd157 Knockout Mice: Transient Improvement by Oxytocin

et al. 2017

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Communication consists of social interaction, recognition, and information transmission. Communication ability is the most affected component in children with autism spectrum disorder (ASD). Recently, we reported that the CD157/BST1 gene is associated with ASD, and that CD157 knockout (Cd157 −/− ) mice display severe impairments in social behavior that are improved by oxytocin (OXT) treatment. Here, we sought to determine whether Cd157 −/− mice can be used as a suitable model for communication deficits by measuring ultrasonic vocalizations (USVs), especially in the early developmental stage. Call number produced in pups due to isolation from dams was higher at postnatal day (PND) 3 in knockout pups than wild-type mice, but was lower at PNDs 7 and 10. Pups of both genotypes had similarly limited voice repertoires at PND 3. Later on, at PNDs 7 and 10, while wild-type pups emitted USVs consisting of six different syllable types, knockout pups vocalized with only two types. This developmental impairment in USV emission was rescued within 30 min by intraperitoneal OXT treatment, but quickly returned to control levels after 120 min, showing a transient effect of OXT. USV impairment was partially observed in Cd157 +/− heterozygous mice, but not in Cd157 −/− adult male mice examined while under courtship. These results demonstrate that CD157 gene deletion results in social communication insufficiencies, and suggests that CD157 is likely involved in acoustic communication. This unique OXT-sensitive developmental delay in Cd157 −/− pups may be a useful model of communicative interaction impairment in ASD.

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Reduced Glutamate Release in Adult BTBR Mouse Model of Autism Spectrum Disorder

Cited by 22 publications

References 45 publications

Autism spectrum disorder: neuropathology and animal models

Autism spectrum disorder: neuropathology and animal models

The BTBR mouse model of idiopathic autism – Current view on mechanisms

Communication Impairment in Ultrasonic Vocal Repertoire during the Suckling Period of Cd157 Knockout Mice: Transient Improvement by Oxytocin

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