La prolifération dendritique et la signalisation ERK élevée pendant le développement néonatal dans un modèle d'autisme de la souris

Aperçu: G.M.

Des modifications de la connectivité réseau et de la fonction mémoire sont fréquemment observées chez les patients "avec autisme", impliquant souvent l'hippocampe. Cependant, des changements spécifiques au cours du début du développement du cerveau conduisant à un fonctionnement perturbé restent largement incertains. Ici, les auteurs ont étudié le développement de l'arbre dendritique des neurones pyramidaux CA1 de l'hippocampe dans le modèle de souris BTBR T + tf / J (BTBR) de l'autisme. 

Comparativement aux animaux con,trôle C57BL / 6J (B6), les longueurs des dendrites apicales et basales étaient significativement plus élevées chez les animaux BTBR néonatals. En outre, les dendrites basales chez les souris BTBR avaient une plus grande complexité de ramification. En revanche, la surface transversale du soma était inchangée.  

Les chercheurs ont aussi observé une densité de neurones pyramidaux CA1 et une épaisseur de la couche neuronale similaire entre les deux souches.  

Ainsi, il y a eu une prolifération spécifique, compartimentée, des dendrites lors du développement précoce chez les animaux BTBR. 

PLoS One. 2017 Jun 13;12(6):e0179409. doi: 10.1371/journal.pone.0179409. eCollection 2017.

Dendritic overgrowth and elevated ERK signaling during neonatal development in a mouse model of autism

Cheng N¹, Alshammari F², Hughes E¹, Khanbabaei M¹, Rho JM³.

Author information

1

Developmental Neurosciences Research Program, Alberta Children's Hospital Research Institute (ACHRI), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

2

O'Brien Centre for the Bachelor of Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

3

Departments of Pediatrics, Clinical Neurosciences, Physiology & Pharmacology, Alberta Children's Hospital Research Institute (ACHRI), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Abstract

Autism spectrum disorder (hereafter referred to as "ASD") is a heterogeneous neurodevelopmental condition characterized by impaired social communication and interactions, and restricted, repetitive activities or interests. Alterations in network connectivity and memory function are frequently observed in autism patients, often involving the hippocampus. However, specific changes during early brain development leading to disrupted functioning remain largely unclear. Here, we investigated the development of dendritic arbor of hippocampal CA1 pyramidal neurons in the BTBR T+tf/J (BTBR) mouse model of autism. BTBR mice display the defining behavioural features of autism, and also exhibit impaired learning and memory. We found that compared to control C57BL/6J (B6) animals, the lengths of both apical and basal dendrites were significantly greater in neonatal BTBR animals. Further, basal dendrites in the BTBR mice had higher branching complexity. In contrast, cross-sectional area of the soma was unchanged. In addition, we observed a similar density of CA1 pyramidal neurons and thickness of the neuronal layer between the two strains. Thus, there was a specific, compartmentalized overgrowth of dendrites during early development in the BTBR animals. Biochemical analysis further showed that the extracellular signal-regulated kinases (ERK) pathway was up-regulated in the hippocampus of neonatal BTBR animals. Since dendritic structure is critical for information integration and relay, our data suggest that altered development of dendrites could potentially contribute to impaired hippocampal function and behavior observed in the BTBR model, and that this might be related to increased activation of the ERK pathway.

PMID:28609458

DOI:10.1371/journal.pone.0179409