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Purcell, Amy E.; Jeon, Ok Hee; Pevsner, Jonathan

doi:10.1023/a:1013290826504

Cited by 18 publications

(4 citation statements)

References 16 publications

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“…In this study, we first generated Nsf +/- mice and found that the mice showed core ASD symptoms, such as abnormal sociability and communication, repetitiveness, and anxiety. Additionally, these mice showed decreased membrane expression of SERT and AMPA receptors in the brain, which were hound in ASD patients ( Purcell et al, 2001a ; Nakamura et al, 2010 ; Iwata et al, 2014 ). The mice also showed impaired PSD and LTD in the hippocampal CA1 region.…”

Section: Discussionmentioning

confidence: 97%

“…Therefore, a decrease in the synaptic GluA1-3 receptor density may reflect a reduction in GluA2 levels in the postsynaptic membrane. In ASD patients, partial loss of NSF transcription and reduced SERT and GluA2 expression at the membrane surface without a decrease in their expression at the mRNA level have been reported ( Purcell et al, 2001a ; Nakamura et al, 2010 ; Iwata et al, 2014 ). The Nsf +/- mouse is a unique model that recapitulates the molecular abnormalities observed in ASD patients.…”

Section: Discussionmentioning

confidence: 99%

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Autistic-Like Behavior and Impairment of Serotonin Transporter and AMPA Receptor Trafficking in N-Ethylmaleimide Sensitive Factor Gene-Deficient Mice

et al. 2021

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Autism spectrum disorder (ASD), characterized by profound impairment in social interactions and communication skills, is the most common neurodevelopmental disorder. Many studies on the mechanisms underlying the development of ASD have focused on the serotonergic system; however, these studies have failed to completely elucidate the mechanisms. We previously identified N-ethylmaleimide-sensitive factor (NSF) as a new serotonin transporter (SERT)-binding protein and described its importance in SERT membrane trafficking and uptake in vitro. In the present study, we generated Nsf+/- mice and investigated their behavioral, neurotransmitter, and neurophysiological phenotypes in vivo. Nsf+/- mice exhibited abnormalities in sociability, communication, repetitiveness, and anxiety. Additionally, Nsf loss led to a decrease in membrane SERT expression in the raphe and accumulation of glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors at the synaptic membrane surface in the hippocampal CA1 region. We found that postsynaptic density and long-term depression were impaired in the hippocampal CA1 region of Nsf+/- mice. Taken together, these findings demonstrate that NSF plays a role in synaptic plasticity and glutamatergic and serotonergic systems, suggesting a possible mechanism by which the gene is linked to the pathophysiology of autistic behaviors.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Autistic-Like Behavior and Impairment of Serotonin Transporter and AMPA Receptor Trafficking in N-Ethylmaleimide Sensitive Factor Gene-Deficient Mice

et al. 2021

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“…Functional magnetic resonance imaging (fMRI) has shown the structural abnormalities in relevant brain structures such as the amygdala, cingulated anterior cortex, and cerebellum (Uddin and Menon, 2009 ). These alterations seem to be associated with neurotransmitters dysregulation with the imbalance between excitation and inhibition in neural circuits (Purcell et al, 2001a , b ).…”

Section: Introductionmentioning

confidence: 99%

Sympathetic, Metabolic Adaptations, and Oxidative Stress in Autism Spectrum Disorders: How Far From Physiology?

et al. 2018

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Autism spectrum disorders (ASD) is a complex and multifaceted neurobehavioral syndrome with no specific cause still identified, despite the worldwide increasing (prevalence for 1,000 children from 6.7 to 14.6, between 2000 and 2012). Many biological and instrumental markers have been suggested as potential predictive factors for the precocious diagnosis during infancy and/or pediatric age. Many studies reported structural and functional abnormalities in the autonomic system in subjects with ASD. Sleep problems in ASD are a prominent feature, having an impact on the social interaction of the patient. Considering the role of orexins (A and B) in wake-sleep circadian rhythm, we could speculate that ASD subjects may present a dysregulation in orexinergic neurotransmission. Conversely, oxidative stress is implicated in the pathophysiology of many neurological disorders. Nonetheless, little is known about the linkage between oxidative stress and the occurrence or the progress of autism and autonomic functioning; some markers, such as heart rate (HR), heart rate variability (HRV), body temperature, and galvanic skin response (GSR), may be altered in the patient with this so complex disorder. In the present paper, we analyzed an autism case report, focusing on the rule of the sympathetic activity with the aim to suggest that it may be considered an important tool in ASD evaluation. The results of this case confirm our hypothesis even if further studies needed.

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“…miRNA transcripts undergo several processing steps occurring first in the nucleus, then in the cytoplasm where the mature 22–25 nucleotide-long miRNA [17], [18] enacts mRNA translational repression or cleavage by binding to the 3′-untranslated region of their respective target mRNAs [19]. Only a few studies have investigated the ASD transcriptome in post-mortem brain samples, so far [20]–[22]. Other studies have used mRNA from lymphoblastoid cell lines or peripheral blood cells isolated from patients [23]–[26].…”

Section: Introductionmentioning

confidence: 99%

Assessing the Impact of Copy Number Variants on miRNA Genes in Autism by Monte Carlo Simulation

et al. 2014

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Autism Spectrum Disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies have investigated the role of de novo Copy Number Variants (CNVs) and microRNAs as important but distinct etiological factors in ASD. We developed a novel computational procedure to assess the potential pathogenic role of microRNA genes overlapping de novo CNVs in ASD patients. Here we show that for chromosomes # 1, 2 and 22 the actual number of miRNA loci affected by de novo CNVs in patients was found significantly higher than that estimated by Monte Carlo simulation of random CNV events. Out of 24 miRNA genes over-represented in CNVs from these three chromosomes only hsa-mir-4436b-1 and hsa-mir-4436b-2 have not been detected in CNVs from non-autistic subjects as reported in the Database of Genomic Variants. Altogether the results reported in this study represent a first step towards a full understanding of how a dysregulated expression of the 24 miRNAs genes affect neurodevelopment in autism. We also propose that the procedure used in this study can be effectively applied to CNVs/miRNA genes association data in other genomic disorders beyond autism.

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Untitled

Cited by 18 publications

References 16 publications

Autistic-Like Behavior and Impairment of Serotonin Transporter and AMPA Receptor Trafficking in N-Ethylmaleimide Sensitive Factor Gene-Deficient Mice

Autistic-Like Behavior and Impairment of Serotonin Transporter and AMPA Receptor Trafficking in N-Ethylmaleimide Sensitive Factor Gene-Deficient Mice

Sympathetic, Metabolic Adaptations, and Oxidative Stress in Autism Spectrum Disorders: How Far From Physiology?

Assessing the Impact of Copy Number Variants on miRNA Genes in Autism by Monte Carlo Simulation

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