Consensus recommendations on Epilepsy in Phelan-McDermid syndrome DOI Creative Commons
I.F.M. de Coo, Sarah Jesse,

Thuy-Linh Le

et al.

European Journal of Medical Genetics, Journal Year: 2023, Volume and Issue: 66(6), P. 104746 - 104746

Published: March 25, 2023

Phelan-McDermid syndrome (PMS) is a 22q13.3 deletion that presents with disturbed development, neurological and psychiatric characteristics, sometimes other comorbidities like seizures. The epilepsy manifests itself in variety of seizure semiologies. Further diagnostics using electroencephalogram (EEG) brain magnetic resonance imaging (MRI) are important conjunction the clinical picture seizures to decide whether anticonvulsant therapy necessary. As part development European consensus guidelines we focussed on prevalence semiology epileptic PMS associated pathogenic variant SHANK3 gene or 22q13 involving SHANK3, order then be able make recommendations regarding diagnosis therapy.

Language: Английский

Cortical interneurons in autism DOI
Anis Contractor, Iryna M. Ethell, Carlos Portera‐Cailliau

et al.

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(12), P. 1648 - 1659

Published: Nov. 29, 2021

Language: Английский

Citations

118
Two-photon calcium imaging of neuronal activity DOI
Christine Grienberger, Andrea Giovannucci, William Zeiger

et al.

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: Sept. 1, 2022

Language: Английский

Citations

80
Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics DOI Creative Commons
Thomas Vaissière,

Sheldon D. Michaelson,

Thomas K. Creson

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 18, 2025

Perception, a cognitive construct, emerges through sensorimotor integration (SMI). The genetic mechanisms that shape SMI required for perception are unknown. Here, we demonstrate in mice expression of the autism/intellectual disability gene, Syngap1, cortical excitatory neurons is formation somatomotor networks promote SMI-mediated perception. Cortical Syngap1 was necessary and sufficient setting tactile sensitivity, sustaining object exploration, promoting learning. Mice with deficient exhibited impaired neural dynamics induced by exploratory touches within cortical-thalamic network promotes attention Disrupted neuronal were associated circuit-specific long-range synaptic connectivity abnormalities. Our data support model where autonomous abilities assembly circuits integrate temporally-overlapping sensory motor signals, process attention. These provide systems-level insights into robust association between ability.

Language: Английский

Citations

2
The Parvalbumin Hypothesis of Autism Spectrum Disorder DOI Creative Commons
Federica Filice, Lucia Janickova,

Thomas Henzi

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Dec. 18, 2020

The prevalence of autism spectrum disorder (ASD)—a type neurodevelopmental disorder—is increasing and is around 2% in North America, Asia, Europe. Besides the known genetic link, environmental, epigenetic, metabolic factors have been implicated ASD etiology. Although highly heterogeneous at behavioral level, comprises a set core symptoms including impaired communication social interaction skills as well stereotyped repetitive behaviors. This has led to suggestion that large part phenotype caused by changes few common signaling pathways, identification which fundamental aim research. Using advanced bioinformatics tools abundantly available data, it possible classify number ASD-associated genes according cellular function pathways. Cellular processes be include gene regulation, synaptic transmission affecting excitation/inhibition balance, neuronal Ca 2+ signaling, development short-/long-range connectivity (circuits networks), mitochondrial function. Such alterations often occur during early postnatal neurodevelopment. Among neurons most affected schizophrenia are those expressing -binding protein parvalbumin (PV). These mainly inhibitory interneurons present many different brain regions humans rodents characterized rapid, non-adaptive firing high energy requirement. PV expression reduced both messenger RNA (mRNA) levels human samples mouse (and schizophrenia) models. PVALB not high-ranking susceptibility/risk for either currently only listed SFARI Gene Archive, we propose supporting evidence Parvalbumin Hypothesis, posits decreased level causally related etiology possibly schizophrenia).

Language: Английский

Citations

76
The Role of the GABAergic System in Diseases of the Central Nervous System DOI
Wen Zhang,

Bingrui Xiong,

Long-Qing Zhang

et al.

Neuroscience, Journal Year: 2021, Volume and Issue: 470, P. 88 - 99

Published: July 6, 2021

Language: Английский

Citations

66
Comparison of SHANK3 deficiency in animal models: phenotypes, treatment strategies, and translational implications DOI Creative Commons
Jan Philipp Delling, Tobias M. Boeckers

Journal of Neurodevelopmental Disorders, Journal Year: 2021, Volume and Issue: 13(1)

Published: Nov. 16, 2021

Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental condition, which characterized by clinical heterogeneity and high heritability. Core symptoms of ASD include deficits in social communication interaction, as well restricted, repetitive patterns behavior, interests, or activities. Many genes have been identified that are associated with an increased risk for ASD. Proteins encoded these often involved processes related to fetal brain development, chromatin modification regulation gene expression general, the structural functional integrity synapses. Genes SH3 multiple ankyrin repeat domains ( SHANK ) family encode crucial scaffolding proteins (SHANK1-3) excitatory synapses other macromolecular complexes. mutations highly more specifically Phelan-McDermid syndrome (PMDS), caused heterozygous 22q13.3-deletion resulting SHANK3 -haploinsufficiency, missense variants. deficiency potential treatment options extensively studied animal models, especially mice, but also rats non-human primates. However, few proposed therapeutic strategies translated into practice yet. Main text This review summarizes literature concerning SHANK3-deficient models. In particular, structural, behavioral, neurological abnormalities described compared, providing broad comprehensive overview. Additionally, underlying pathophysiologies possible treatments investigated models discussed evaluated respect their effect on ASD- PMDS-associated phenotypes. Conclusions Animal generated various genetic strategies, determine composition residual SHANK3-isoforms affected cell types, show phenotypes resembling PMDS. The phenotypic across studies resembles variation severity human PMDS patients. Multiple tested might lead translational implications patients and/or Future should explore effects new approaches target haploinsufficiency, like CRISPR-mediated activation promotors.

Language: Английский

Citations

65
Improvement of sensory deficits in fragile X mice by increasing cortical interneuron activity after the critical period DOI Creative Commons
Nazim Kourdougli, Anand Suresh, Benjamin Liu

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(18), P. 2863 - 2880.e6

Published: July 13, 2023

Changes in the function of inhibitory interneurons (INs) during cortical development could contribute to pathophysiology neurodevelopmental disorders. Using all-optical vivo approaches, we find that parvalbumin (PV) INs and their immature precursors are hypoactive transiently decoupled from excitatory neurons postnatal mouse somatosensory cortex (S1) Fmr1 KO mice, a model fragile X syndrome (FXS). This leads loss (PV-INs) both mice humans with FXS. Increasing activity future PV-INs neonatal restores PV-IN density ameliorates transcriptional dysregulation S1, but not circuit dysfunction. Critically, administering an allosteric modulator Kv3.1 channels after S1 critical period does rescue dynamics tactile defensiveness. Symptoms FXS related disorders be mitigated by targeting PV-INs.

Language: Английский

Citations

30
Impaired cerebellar plasticity hypersensitizes sensory reflexes in SCN2A-associated ASD DOI Creative Commons
Chenyu Wang, Kimberly D. Derderian,

Elizabeth Hamada

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(9), P. 1444 - 1455.e5

Published: Feb. 26, 2024

Children diagnosed with autism spectrum disorder (ASD) commonly present sensory hypersensitivity or abnormally strong reactions to stimuli. Such can be overwhelming, causing high levels of distress that contribute markedly the negative aspects disorder. Here, we identify a mechanism underlies in sensorimotor reflex found altered humans and mice loss function ASD risk-factor gene SCN2A. The cerebellum-dependent vestibulo-ocular (VOR), which helps maintain one's gaze during movement, was hypersensitized due deficits cerebellar synaptic plasticity. Heterozygous SCN2A-encoded Na

Language: Английский

Citations

13
Behavioral Abnormalities, Cognitive Impairments, Synaptic Deficits, and Gene Replacement Therapy in a CRISPR Engineered Rat Model of 5p15.2 Deletion Associated With Cri du Chat Syndrome DOI Creative Commons
Jingjing Shen, Yan Wang, Yang Liu

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Abstract The Cri du Chat Syndrome (CdCS), a devastating genetic disorder caused by deletion on chromosome 5p, faces challenges in finding effective treatments and accurate animal models. Using CRISPR‐Cas9, novel CdCS rat model with 2q22 is developed, mirroring common alteration patients. This exhibits pronounced deficits social behavior, cognition, anxiety, accompanied neuronal abnormalities immune dysregulation key brain regions such as the hippocampus medial prefrontal cortex (mPFC). immunostaining RNA‐seq analyses provide new insights into pathogenesis, revealing inflammatory processes. Importantly, it demonstrated that early gene replacement therapy AAV‐ Ctnnd2 alleviates cognitive impairments rats, highlighting potential for intervention. However, effectiveness of this confined to developmental stages does not fully restore all symptoms. findings deepen understanding pathogenesis suggest promising therapeutic directions.

Language: Английский

Citations

1
Parvalbumin and parvalbumin chandelier interneurons in autism and other psychiatric disorders DOI
Pablo Juárez, Verónica Martínez‐Cerdeño

Frontiers in Psychiatry, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 12, 2022

Parvalbumin (PV) is a calcium binding protein expressed by inhibitory fast-spiking interneurons in the cerebral cortex. By generating fast stream of action potentials, PV+ provide quick and stable input to pyramidal neurons contribute generation gamma oscillations Their fast-firing rates, while advantageous for regulating cortical signaling, also leave them vulnerable metabolic stress. Chandelier (Ch) cells are type interneuron that modulate output synchronize spikes within neuron populations directly innervating axon initial segment. Changes morphology and/or function interneurons, mostly Ch cells, linked neurological disorders. In ASD, number decreased across several areas. have been schizophrenia, epilepsy, bipolar disorder. Herein, we review role PV cell alterations ASD other psychiatric

Language: Английский

Citations

37