Arias-Aragon_2023_iScience_26_106868

Reference

Title : A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity - Arias-Aragon_2023_iScience_26_106868
Author(s) : Arias-Aragon F , Tristan-Clavijo E , Martinez-Gallego I , Robles-Lanuza E , Coatl-Cuaya H , Martin-Cuevas C , Sanchez-Hidalgo AC , Rodriguez-Moreno A , Martinez-Mir A , Scholl FG
Ref : iScience , 26 :106868 , 2023
Abstract :

Alzheimer's disease (AD) is characterized by memory impairments and age-dependent synapse loss. Experimental and clinical studies have shown decreased expression of the glutamatergic protein Neuroligin-1 (Nlgn1) in AD. However, the consequences of a sustained reduction of Nlgn1 are unknown. Here, we generated a knockin mouse that reproduces the NLGN1 Thr271fs mutation, identified in heterozygosis in a familial case of AD. We found that Nlgn1 Thr271fs mutation abolishes Nlgn1 expression in mouse brain. Importantly, heterozygous Nlgn1 Thr271fs mice showed delay-dependent amnesia for recognition memory. Electrophysiological recordings uncovered age-dependent impairments in basal synaptic transmission and long-term potentiation (LTP) in CA1 hippocampal neurons of heterozygous Nlgn1 Thr271fs mice. In contrast, homozygous Nlgn1 Thr271fs mice showed impaired fear-conditioning memory and normal basal synaptic transmission, suggesting unshared mechanisms for a partial or total loss of Nlgn1. These data suggest that decreased Nlgn1 may contribute to the synaptic and memory deficits in AD.

PubMedSearch : Arias-Aragon_2023_iScience_26_106868
PubMedID: 37260747
Gene_locus related to this paper: human-NLGN1

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Arias-Aragon F, Tristan-Clavijo E, Martinez-Gallego I, Robles-Lanuza E, Coatl-Cuaya H, Martin-Cuevas C, Sanchez-Hidalgo AC, Rodriguez-Moreno A, Martinez-Mir A, Scholl FG (2023)
A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity
iScience 26 :106868

Arias-Aragon F, Tristan-Clavijo E, Martinez-Gallego I, Robles-Lanuza E, Coatl-Cuaya H, Martin-Cuevas C, Sanchez-Hidalgo AC, Rodriguez-Moreno A, Martinez-Mir A, Scholl FG (2023)
iScience 26 :106868