Aging of the NMDA receptor: from a mouse's point of view

Abstract

Our elderly population is growing and declines in cognitive abilities, such as memory, can be costly, because it can interfere with a person's ability to live independently. The NMDA receptor is very important for many different forms of memory and this receptor is negatively affected by aging. This review examines the progress that has been made recently in characterizing selective vulnerabilities of different subunits and splice variants of the NMDA receptor to normal aging in C57BL/6 mice. Evidence is also presented for changes in the relationships of NMDA receptors to plasticity across aging. Recent interventions show that enhancing NMDA receptors in aged individuals is associated with improvements in memory, but mouse models of neurodegenerative diseases suggest that finding the right balance between too little and too much NMDA receptor activity will be the key to enhancing memory without inducing pathology.

Figure 1. Schematic diagram of the eight splice variants of the GluN1 subunit and the nomenclature used to identify each

There is one N-terminal cassette, N1, and two C-terminal cassettes, C1 and C2. In the absence of C2, there is an additional sequence, C2′, with a new stop codon. The arrows at the bottom of the figure indicate the cassette identified by each subscript. Subscripts: 1 indicates the presence of the cassette, 0 indicates the absence of the cassette. Please note that a 0 in the C2 position (third subscript) indicates the presence of the C2′ sequence. An X is used in the text to indicate both the presence and absence of a cassette. TM: Transmembrane domain. Adapted from [12,77].