Éléments fondamentaux dans l'autisme: de la neurogenèse et de la croissance des neurites à la plasticité synaptique

Aperçu: G.M.

Le trouble du spectre autistique (TSA) est un ensemble de troubles neurodéveloppementaux avec une prévalence élevée et un impact sur la société. Les TSA sont caractérisés par des déficits dans le comportement social et la fonction cognitive. Il existe une forte base génétique sous-jacente aux TSA, qui est très hétérogène; Cependant, plusieurs études ont souligné l'implication de processus clés, y compris la neurogenèse, la croissance des neurites, la synaptogenèse et la plasticité synaptique dans la physiopathologie des troubles neurodéveloppementaux. 

Dans cette revue d'articles, les auteurs se sont intéressés aux principaux gènes et voies de signalisation impliqués dans les TSA. et aux études cellulaires, moléculaires et fonctionnelles qui ont mis en lumière des voies dérégulées communes en utilisant des preuves in vitro, in vivo et humaines.

Front Cell Neurosci. 2017 Nov 20;11:359. doi: 10.3389/fncel.2017.00359. eCollection 2017.

Fundamental Elements in Autism: From Neurogenesis and Neurite Growth to Synaptic Plasticity

Gilbert J¹, Man HY^1,2.

Author information

1

Department of Biology, Boston University, Boston, MA, United States.

2

Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, MA, United States.

Abstract

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders with a high prevalence and impact on society. ASDs are characterized by deficits in both social behavior and cognitive function. There is a strong genetic basis underlying ASDs that is highly heterogeneous; however, multiple studies have highlighted the involvement of key processes, including neurogenesis, neurite growth, synaptogenesis and synaptic plasticity in the pathophysiology of neurodevelopmental disorders. In this review article, we focus on the major genes and signaling pathways implicated in ASD and discuss the cellular, molecular and functional studies that have shed light on common dysregulated pathways using in vitro, in vivo and human evidence. Highlights Autism spectrum disorder (ASD) has a prevalence of 1 in 68 children in the United States.ASDs are highly heterogeneous in their genetic basis.ASDs share common features at the cellular and molecular levels in the brain.Most ASD genes are implicated in neurogenesis, structural maturation, synaptogenesis and function.

PMID:29209173

PMCID:PMC5701944

DOI:10.3389/fncel.2017.00359

Mov10 supprime les rétroéléments et régule le développement et le fonctionnement neuronal dans le cerveau en développement

Aperçu: G.M.

Le virus de la leucémie de Moloney 10 (Mov10) est une hélicase (source Wiki: protéines qui utilisent l‘énergie d’hydrolyse de l’ATP ou du GTP pour catalyser l’ouverture d’acides nucléiques (ADN ou ARN) appariés sous forme double brins. ) d'ARN qui intervient sur l'accès du complexe RISC aux ARN messagers (ARNm).  

Mov10 est essentiel pour le développement neuronal normal et la fonction du cerveau. Mov10 se lie préférentiellement aux ARN impliqués dans la liaison de l'actine, la projection neuronale et le cytosquelette. Il s'agit d'une fonction complètement nouvelle et extrêmement importante pour Mov10 dans le développement neuronal et établit un précédent pour Mov10 être un candidat important dans les troubles neurologiques qui ont des causes cytoarchitecturales sous-jacentes comme l'autisme et la maladie d'Alzheimer.

BMC Biol. 2017 Jun 29;15(1):54. doi: 10.1186/s12915-017-0387-1.

Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain

Skariah G¹, Seimetz J², Norsworthy M³, Lannom MC³, Kenny PJ³, Elrakhawy M³, Forsthoefel C⁴, Drnevich J⁵, Kalsotra A^2,4, Ceman S^6,7,8.

Author information

1

Neuroscience Program, University of Illinois-Urbana Champaign, Urbana, IL, 61801, USA.

2

Biochemistry, University of Illinois-Urbana Champaign, Urbana, IL, 61801, USA.

3

Cell and Developmental Biology, University of Illinois-Urbana Champaign, Urbana, IL, 61801, USA.

4

College of Medicine, University of Illinois-Urbana Champaign, Urbana, IL, 61801, USA.

5

High-Performance Biological Computing, Roy J. Carver Biotechnology Center, University of Illinois-Urbana Champaign, Urbana, IL, 61801, USA.

6

Neuroscience Program, University of Illinois-Urbana Champaign, Urbana, IL, 61801, USA. sceman@illinois.edu.

7

Cell and Developmental Biology, University of Illinois-Urbana Champaign, Urbana, IL, 61801, USA. sceman@illinois.edu.

8

College of Medicine, University of Illinois-Urbana Champaign, Urbana, IL, 61801, USA. sceman@illinois.edu.

Abstract

BACKGROUND:

Moloney leukemia virus 10 (Mov10) is an RNA helicase that mediates access of the RNA-induced silencing complex to messenger RNAs (mRNAs). Until now, its role as an RNA helicase and as a regulator of retrotransposons has been characterized exclusively in cell lines. We investigated the role of Mov10 in the mouse brain by examining its expression over development and attempting to create a Mov10 knockout mouse. Loss of both Mov10 copies led to early embryonic lethality.

RESULTS:

Mov10 was significantly elevated in postnatal murine brain, where it bound retroelement RNAs and mRNAs. Mov10 suppressed retroelements in the nucleus by directly inhibiting complementary DNA synthesis, while cytosolic Mov10 regulated cytoskeletal mRNAs to influence neurite outgrowth. We verified this important function by observing reduced dendritic arborization in hippocampal neurons from the Mov10 heterozygote mouse and shortened neurites in the Mov10 knockout Neuro2A cells. Knockdown of Fmrp also resulted in shortened neurites. Mov10, Fmrp, and Ago2 bound a common set of mRNAs in the brain. Reduced Mov10 in murine brain resulted in anxiety and increased activity in a novel environment, supporting its important role in the development of normal brain circuitry.

CONCLUSIONS:

Mov10 is essential for normal neuronal development and brain function. Mov10 preferentially binds RNAs involved in actin binding, neuronal projection, and cytoskeleton. This is a completely new and critically important function for Mov10 in neuronal development and establishes a precedent for Mov10 being an important candidate in neurological disorders that have underlying cytoarchitectural causes like autism and Alzheimer's disease.

PMID:28662698

DOI:10.1186/s12915-017-0387-1