Dysregulated Ca2+-Permeable AMPA Receptor Signaling in Neural Progenitors Modeling Fragile X Syndrome

Claudia Elisabetta Danesi, Kari Pekka Keinänen, Maija Liisa Castren

Tutkimustuotos: ArtikkelijulkaisuKatsausartikkeliTieteellinenvertaisarvioitu

Kuvaus

Fragile X syndrome (FXS) is a neurodevelopmental disorder that represents a common cause of intellectual disability and is a variant of autism spectrum disorder (ASD). Studies that have searched for similarities in syndromic and non-syndromic forms of ASD have paid special attention to alterations of maturation and function of glutamatergic synapses. Copy number variations (CNVs) in the loci containing genes encoding alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) subunits are associated with ASD in genetic studies. In FXS, dysregulated AMPAR subunit expression and trafficking affect neural progenitor differentiation and synapse formation and neuronal plasticity in the mature brain. Decreased expression of GluA2, the AMPAR subunit that critically controls Ca2+-permeability, and a concomitant increase in Ca2+-permeable AMPARs (CP-AMPARs) in human and mouse FXS neural progenitors parallels changes in expression of GluA2-targeting microRNAs (miRNAs). Thus, posttranscriptional regulation of GluA2 by miRNAs and subsequent alterations in calcium signaling may contribute to abnormal synaptic function in FXS and, by implication, in some forms of ASD.

Alkuperäiskielienglanti
Artikkeli2
LehtiFrontiers in Synaptic Neuroscience
Vuosikerta11
Sivumäärä8
ISSN1663-3563
DOI - pysyväislinkit
TilaJulkaistu - 8 helmikuuta 2019
OKM-julkaisutyyppiA2 Katsausartikkeli tieteellisessä aikakauslehdessä

Tieteenalat

  • 3112 Neurotieteet

Lainaa tätä

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title = "Dysregulated Ca2+-Permeable AMPA Receptor Signaling in Neural Progenitors Modeling Fragile X Syndrome",
abstract = "Fragile X syndrome (FXS) is a neurodevelopmental disorder that represents a common cause of intellectual disability and is a variant of autism spectrum disorder (ASD). Studies that have searched for similarities in syndromic and non-syndromic forms of ASD have paid special attention to alterations of maturation and function of glutamatergic synapses. Copy number variations (CNVs) in the loci containing genes encoding alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) subunits are associated with ASD in genetic studies. In FXS, dysregulated AMPAR subunit expression and trafficking affect neural progenitor differentiation and synapse formation and neuronal plasticity in the mature brain. Decreased expression of GluA2, the AMPAR subunit that critically controls Ca2+-permeability, and a concomitant increase in Ca2+-permeable AMPARs (CP-AMPARs) in human and mouse FXS neural progenitors parallels changes in expression of GluA2-targeting microRNAs (miRNAs). Thus, posttranscriptional regulation of GluA2 by miRNAs and subsequent alterations in calcium signaling may contribute to abnormal synaptic function in FXS and, by implication, in some forms of ASD.",
keywords = "AMPA, AUTISM SPECTRUM DISORDERS, DIFFERENTIATION, EXPRESSION, FMRP, GENE, GLUTAMATE RECEPTORS, GluA2, MENTAL-RETARDATION PROTEIN, MOUSE MODEL, SILENT SYNAPSES, SYNAPTIC PLASTICITY, autism, fragile X syndrome, miR-181, miRNA, neural progenitor, plasticity, 3112 Neurosciences",
author = "Danesi, {Claudia Elisabetta} and Kein{\"a}nen, {Kari Pekka} and Castren, {Maija Liisa}",
year = "2019",
month = "2",
day = "8",
doi = "10.3389/fnsyn.2019.00002",
language = "English",
volume = "11",
journal = "Frontiers in Synaptic Neuroscience",
issn = "1663-3563",
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Dysregulated Ca2+-Permeable AMPA Receptor Signaling in Neural Progenitors Modeling Fragile X Syndrome. / Danesi, Claudia Elisabetta; Keinänen, Kari Pekka; Castren, Maija Liisa.

julkaisussa: Frontiers in Synaptic Neuroscience, Vuosikerta 11, 2, 08.02.2019.

Tutkimustuotos: ArtikkelijulkaisuKatsausartikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Dysregulated Ca2+-Permeable AMPA Receptor Signaling in Neural Progenitors Modeling Fragile X Syndrome

AU - Danesi, Claudia Elisabetta

AU - Keinänen, Kari Pekka

AU - Castren, Maija Liisa

PY - 2019/2/8

Y1 - 2019/2/8

N2 - Fragile X syndrome (FXS) is a neurodevelopmental disorder that represents a common cause of intellectual disability and is a variant of autism spectrum disorder (ASD). Studies that have searched for similarities in syndromic and non-syndromic forms of ASD have paid special attention to alterations of maturation and function of glutamatergic synapses. Copy number variations (CNVs) in the loci containing genes encoding alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) subunits are associated with ASD in genetic studies. In FXS, dysregulated AMPAR subunit expression and trafficking affect neural progenitor differentiation and synapse formation and neuronal plasticity in the mature brain. Decreased expression of GluA2, the AMPAR subunit that critically controls Ca2+-permeability, and a concomitant increase in Ca2+-permeable AMPARs (CP-AMPARs) in human and mouse FXS neural progenitors parallels changes in expression of GluA2-targeting microRNAs (miRNAs). Thus, posttranscriptional regulation of GluA2 by miRNAs and subsequent alterations in calcium signaling may contribute to abnormal synaptic function in FXS and, by implication, in some forms of ASD.

AB - Fragile X syndrome (FXS) is a neurodevelopmental disorder that represents a common cause of intellectual disability and is a variant of autism spectrum disorder (ASD). Studies that have searched for similarities in syndromic and non-syndromic forms of ASD have paid special attention to alterations of maturation and function of glutamatergic synapses. Copy number variations (CNVs) in the loci containing genes encoding alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) subunits are associated with ASD in genetic studies. In FXS, dysregulated AMPAR subunit expression and trafficking affect neural progenitor differentiation and synapse formation and neuronal plasticity in the mature brain. Decreased expression of GluA2, the AMPAR subunit that critically controls Ca2+-permeability, and a concomitant increase in Ca2+-permeable AMPARs (CP-AMPARs) in human and mouse FXS neural progenitors parallels changes in expression of GluA2-targeting microRNAs (miRNAs). Thus, posttranscriptional regulation of GluA2 by miRNAs and subsequent alterations in calcium signaling may contribute to abnormal synaptic function in FXS and, by implication, in some forms of ASD.

KW - AMPA

KW - AUTISM SPECTRUM DISORDERS

KW - DIFFERENTIATION

KW - EXPRESSION

KW - FMRP

KW - GENE

KW - GLUTAMATE RECEPTORS

KW - GluA2

KW - MENTAL-RETARDATION PROTEIN

KW - MOUSE MODEL

KW - SILENT SYNAPSES

KW - SYNAPTIC PLASTICITY

KW - autism

KW - fragile X syndrome

KW - miR-181

KW - miRNA

KW - neural progenitor

KW - plasticity

KW - 3112 Neurosciences

U2 - 10.3389/fnsyn.2019.00002

DO - 10.3389/fnsyn.2019.00002

M3 - Review Article

VL - 11

JO - Frontiers in Synaptic Neuroscience

JF - Frontiers in Synaptic Neuroscience

SN - 1663-3563

M1 - 2

ER -