Article
A Neuroligin-1 mutation associated with Alzheimer’s disease produces memory and age-dependent impairments in hippocampal plasticity
Author/s | Arias-Aragón, Francisco
Tristán Clavijo, Enriqueta Martínez Gallego, Irene Robles Lanuza, Estefanía Coatl-Cuaya, Heriberto Martín-Cuevas, Celia Sánchez Hidalgo, Ana Carmen Rodríguez Moreno, Antonio Martínez Mir, Amalia Gómez Scholl, Francisco Manuel |
Department | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Publication Date | 2023-05-13 |
Deposit Date | 2024-07-30 |
Published in |
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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. ... 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. |
Funding agencies | European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) Junta de Andalucía Ministerio de Ciencia, Innovación y Universidades (MICINN). España Ministerio de Economia, Industria y Competitividad (MINECO). España Formación de Profesorado Universitario predoctoral fellowship del Ministerio de Universidades |
Project ID. | PID2019107677GBI00
FPU 17/04283 BES-2016-076579 P11- CVI-7599 P20_00881 RTI2018-101886-B- 100 PROYEXCEL_00573 |
Citation | Arias-Aragón, F., Tristán Clavijo, E., Martínez Gallego, I., Robles Lanuza, E., Coatl-Cuaya, H., Martín-Cuevas, C.,...,Gómez Scholl, F.M. (2023). A Neuroligin-1 mutation associated with Alzheimer’s disease produces memory and age-dependent impairments in hippocampal plasticity. iScience, 26 (6), 106868. https://doi.org/10.1016/j.isci.2023.106868. |
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