Maintenance of superior learning and memory function in NR2B transgenic mice during ageing

Abstract

Brain ageing represents a general and evolutionarily conserved phenomenon and is marked by gradual declines in cognitive functions such as learning and memory. As a synaptic coincidence detector, the N-methyl-d-aspartate (NMDA) receptor is known to be essential for the induction of synaptic plasticity and memory formation. Here, we test the hypothesis that up-regulation of NR2B expression is beneficial for learning and memory in the aged animals. Our in vitro recordings show that the aged transgenic mice with the forebrain-specific overexpression of the NR2B subunit indeed exhibit more robust hippocampal long-term potentiation (LTP) induced by either high-frequency stimulation or theta-stimulation protocol. Furthermore, those aged NR2B transgenic mice consistently outperform their wild-type littermates in five different learning and memory tests, namely, novel object recognition, contextual and cued fear conditioning, spatial reference memory, and spatial working memory T-maze task. Thus, we conclude that increased expression of NR2B in the forebrain improves learning and memory function in the aged brain.

Caloric Restriction Increases Learning Consolidation and Facilitates Synaptic Plasticity through Mechanisms Dependent on NR2B Subunits of the NMDA Receptor

“…Mice overexpressing NR2B subunit in forebrain also display enhancement in LTP and learning with respect to control mice in healthy mice (Tang et al, 1999(Tang et al, , 2001White and Youngentob, 2004) as well as in old mice (Cao et al, 2007). Thus, the increase in expression and/or activity of NR2B subunits could improve cognitive capabilities in mice.…”

“…It has been proposed that NR2A-and NR2B-type NMDARs induce LTP and long-term depression, respectively (Liu et al, 2004;Massey et al, 2004). In contrast, a role for NR2B subunits in LTP has been demonstrated in mice with NR2B overexpression in the forebrain (Tang et al, 1999;Wong et al, 2002;Cao et al, 2007) or by overexpression of NR2B subunits in brain slices (Barria and Malinow, 2005). Also, NR2B-dependent LTP was observed in mice with no or impaired NR2A signaling (Kiyama et al, 1998;Kohr et al, 2003) and when using NR2-specific antagonists (Berberich et al, 2005).…”

In VivoEvidence for NMDA Receptor-Mediated Excitotoxicity in a Murine Genetic Model of Huntington Disease

“…NR2B transgenic mice display normal growth, body weight, and survival. No anatomic abnormalities are documented in this line, and NR2B transgenic mice maintain superior performance in learning and memory tasks up to at least 20 months of age (Tang et al, 1999;Cao et al, 2007). NR2B subunit expression declines with normal aging (Magnusson et al, 2002).…”

A novel derivative of xanomeline improved memory function in aged mice

“…Novel object recognition test was performed as described by Cao X et al [13] Briefly, mice were handled individually and habituated to an open field box (500* 500* 250 mm) for 5 min daily for 3 d. During the training session, two objects were placed in the center of the box and each mouse was given 5 min to explore. The time spent in exploring each object was recorded.…”

“…The ratio of the amount of time spent in exploring the novel object to the total time spent in exploring both objects (preference index) was calculated to evaluate the recognition memory of each mouse. 2.5 Hippocampal slice recording Hippocampal slices were prepared from the aged C57BL/6J mice according to procedures previously described [13] . Briefly, the mice were rapidly decapitated and brain slices containing the hippocampus were extracted using a vibratome.…”