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Selective disruption of synaptic NMDA receptors of the hippocampal trisynaptic circuit in Aß pathology.
Alfaro-Ruiz, Rocio; Martín-Belmonte, Alejandro; Aguado, Carolina; Moreno-Martínez, Ana Esther; Fukazawa, Yugo; Luján, Rafael.
Afiliação
  • Alfaro-Ruiz R; Synaptic Structure Laboratory, Departamento de Ciencias Médicas, Facultad de Medicina, Instituto de Biomedicina de la UCLM (IB-UCLM), Universidad Castilla-La Mancha, Campus Biosanitario, C/ Almansa 14, Albacete, 02008, Spain.
  • Martín-Belmonte A; Laboratorio de Estructura Sináptica, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Albacete, Spain.
  • Aguado C; Synaptic Structure Laboratory, Departamento de Ciencias Médicas, Facultad de Medicina, Instituto de Biomedicina de la UCLM (IB-UCLM), Universidad Castilla-La Mancha, Campus Biosanitario, C/ Almansa 14, Albacete, 02008, Spain.
  • Moreno-Martínez AE; Pharmacology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat, 08907, Spain.
  • Fukazawa Y; Neuropharmacology and Pain Group, Neuroscience Program, Institut d'Investigació Biomèdica de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, 08907, Spain.
  • Luján R; Synaptic Structure Laboratory, Departamento de Ciencias Médicas, Facultad de Medicina, Instituto de Biomedicina de la UCLM (IB-UCLM), Universidad Castilla-La Mancha, Campus Biosanitario, C/ Almansa 14, Albacete, 02008, Spain.
Biol Res ; 57(1): 56, 2024 Aug 22.
Article em En | MEDLINE | ID: mdl-39175009
ABSTRACT
Synaptic dysfunction is an early feature in Alzheimer's disease (AD) pathogenesis and a major morphological correlate of memory deficits. Given the main synaptic location of N-methyl-D-aspartate receptors (NMDARs), their dysregulation has been implicated in these pathological effects. Here, to detect possible alterations in the expression and synaptic localisation of the GluN1 subunit in the brain of amyloidogenic APP/PS1 mice, we employed histoblot and SDS-digested freeze-fracture replica labelling (SDS-FRL) techniques. Histoblots showed that GluN1 expression was significantly reduced in the hippocampus in a layer-dependent manner, in the cortex and the caudate putamen of APP/PS1 transgenic mice at 12 months of age but was unaltered at 1 and 6 months. Using quantitative SDS-FRL, we unravelled the molecular organisation of GluN1 in seven excitatory synapse populations at a high spatial resolution in the CA1 and CA3 fields and the DG of the hippocampus in 12-month-old APP/PS1 mice. In the CA1 field, the labelling density for GluN1 in the excitatory synapses established on spines and interneurons, was significantly reduced in APP/PS1 mice compared to age-matched wild-type mice in the stratum lacunosum-moleculare but unaltered in the stratum radiatum. In the CA3 field, synaptic GluN1 was reduced in mossy fibre-CA3 pyramidal cell synapses but unaltered in the A/C-CA3 pyramidal cell synapses. In the DG, the density of GluN1 in granule cell-perforant pathway synapses was reduced in APP/PS1 mice. Altogether, our findings provide evidence of specific alterations of synaptic GluN1 in the trisynaptic circuit of the hippocampus in Aß pathology. This differential vulnerability in the disruption of NMDARs may be involved in the mechanisms causing abnormal network activity of the hippocampal circuit and cognitive impairment characteristic of APP/PS1 mice.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinapses / Receptores de N-Metil-D-Aspartato / Doença de Alzheimer / Hipocampo Limite: Animals Idioma: En Revista: Biol Res Assunto da revista: BIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Espanha País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinapses / Receptores de N-Metil-D-Aspartato / Doença de Alzheimer / Hipocampo Limite: Animals Idioma: En Revista: Biol Res Assunto da revista: BIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Espanha País de publicação: Reino Unido