Titre :

Integration of Microfluidic Devices with Microelectrode Arrays to Functionally Assay Amyloid-β-Induced Synaptotoxicity.

Auteur(s) :

Lefebvre, Camille [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Vreulx, Anaïs-Camille [Auteur]
Excellence Laboratory LabEx DISTALZ
Dumortier, Corentin [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Bégard, Séverine [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Gelle, Carla [Auteur]
Excellence Laboratory LabEx DISTALZ
Siedlecki-Wullich, Dolores [Auteur]
Excellence Laboratory LabEx DISTALZ
Colin, Morvane [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Kilinc, Devrim [Auteur]
Excellence Laboratory LabEx DISTALZ
Halliez, Sophie [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172

Titre de la revue :

ACS Biomaterials Science & Engineering

Nom court de la revue :

ACS Biomater Sci Eng

Numéro :

10

Pagination :

1856–1868

Éditeur :

American Chemical Society

Date de publication :

2024-02-22

ISSN :

2373-9878

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Alzheimer’s disease (AD) is a neurodegenerative disease and the most frequent cause of dementia. It is characterized by the accumulation in the brain of two pathological protein aggregates: amyloid-β peptides (Aβ) and ...
Lire la suite >Alzheimer’s disease (AD) is a neurodegenerative disease and the most frequent cause of dementia. It is characterized by the accumulation in the brain of two pathological protein aggregates: amyloid-β peptides (Aβ) and abnormally phosphorylated tau. The progressive cognitive decline observed in patients strongly correlates with the synaptic loss. Many lines of evidence suggest that soluble forms of Aβ accumulate into the brain where they cause synapse degeneration. Stopping their spreading and/or targeting the pathophysiological mechanisms leading to synaptic loss would logically be beneficial for the patients. However, we are still far from understanding these processes. Our objective was therefore to develop a versatile model to assay and study Aβ-induced synaptotoxicity. We integrated a microfluidic device that physically isolates synapses from presynaptic and postsynaptic neurons with a microelectrode array. We seeded mouse primary cortical cells in the presynaptic and postsynaptic chambers. After functional synapses have formed in the synaptic chamber, we exposed them to concentrated conditioned media from cell lines overexpressing the wild-type or mutated amyloid precursor protein and thus secreting different levels of Aβ. We recorded the neuronal activity before and after exposition to Aβ and quantified Aβ’s effects on the connectivity between presynaptic and postsynaptic neurons. We observed that the application of Aβ on the synapses for 48 h strongly decreased the interchamber connectivity without significantly affecting the neuronal activity in the presynaptic or postsynaptic chambers. Thus, through this model, we are able to functionally assay the impact of Aβ peptides (or other molecules) on synaptic connectivity and to use the latter as a proxy to study Aβ-induced synaptotoxicity. Moreover, since the presynaptic, postsynaptic, and synaptic chambers can be individually targeted, our assay provides a powerful tool to evaluate the involvement of candidate genes in synaptic vulnerability and/or test therapeutic strategies for AD.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Date de dépôt :

2024-02-25T22:01:17Z
2024-10-16T07:13:47Z