Serotonin neuron abnormalities in the BTBR mouse model of autism

Guo, Yueping; Commons, Kathryn G.

doi:10.1002/aur.1665

Cited by 41 publications

(36 citation statements)

References 61 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 Modelssupporting

confidence: 80%

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 Modelssupporting

confidence: 80%

Autism spectrum disorder: neuropathology and animal models

et al. 2017

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“…In fact, increasing cerebral cortical noradrenaline levels has been suggested in the therapeutic approaches for attention deficit hyperactivity disorder (ADHD) (del Campo et al, ), a disorder that shares symptoms with ASD, in terms of social and other behavioural impairments (de Boo and Prins, ). In BTBR mice, a strain that exhibits reduced play and social approach behaviour and is utilized as an animal model of ASD, noradrenaline is significantly decreased in the cortex, striatum and hippocampus when compared to C57BL/6J mice (Guo and Commons, ).…”

Section: Discussionmentioning

confidence: 99%

Embryonic exposure to valproic acid affects the histaminergic system and the social behaviour of adult zebrafish (Danio rerio)

Baronio

Puttonen

Sundvik

et al. 2018

British J Pharmacology

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“…Increased 8-OH-DPAT-stimulated GTPγS binding in the BTBR hippocampus indicated an elevated capacity of 5HT 1A receptors to activate G-proteins (Gould et al 2011). At the same time, fewer serotonergic cells were reported in the hippocampus of BTBR mice as compared to B6 mice (Guo and Commons, 2016). This, however, was compensated by increased number of serotonergic cells in brain areas projecting to the hippocampus, especially in the median raphe.…”

Section: Molecular Mechanismsmentioning

confidence: 99%

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

Meyza

Blanchard

2017

Neuroscience & Biobehavioral Reviews

124

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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Serotonin neuron abnormalities in the BTBR mouse model of autism

Cited by 41 publications

References 61 publications

Autism spectrum disorder: neuropathology and animal models

Autism spectrum disorder: neuropathology and animal models

Embryonic exposure to valproic acid affects the histaminergic system and the social behaviour of adult zebrafish (Danio rerio)

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

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