N‐methyl‐D‐aspartate receptors, synaptic plasticity, and Alzheimer's disease

Abstract

The NMDA (N-methyl-n-aspartate) excitatory amino acid receptor mediates a potent excitatory response in many regions of the CNS and plays a key role in excitotoxicity and synaptic plasticity. Results from radioligand-binding studies indicate that NMDA agonists and antagonists preferentially bind to differing populations of NMDA receptors. The distribution of NMDA receptors as labeled by the agonist L-[3H]glutamate differs from that obtained with the radiolabeled antagonist [3H]3-((?2-carboxypiperazine-4-yl)-propyl-lphosphonic acid ([3H]CPP). In addition, NMDA agonists and antagonists display complementary regional variations in their ability to displace L-[3H]glutamate binding. At least some of the differences between agonist and antagonist-binding properties can be accounted for by suggesting that glycine converts the NMDA receptor from an antagonist-preferring state into an agonist-preferring state. Since NMDA and other excitatory amino acid receptor functions are necessary for synaptic function, certain forms of synaptic plasticity, and learning, we have evaluated their status in Alzheimer's disease (AD). Using radioligandbinding techniques, we find that NMDA receptors are generally preserved in the course of AD pathology in the human hippocampus in spite of partial cell loss. Kainate receptors, on the other hand, display a redistribution within the hippocampus. This redistribution corresponds to an apparent synaptic reorganization owing to the loss of input from the entorhinal cortex. The response of both the NMDA and kainate receptor systems may be adaptive plastic responses that attempt to maintain hippocampal function that is compromised by AD. However, these mechanisms may also render the hippocampus more vulnerable to damage following excessive neuronal activation. Received final version

Pharmacological studies of a rat spatial delayed nonmatch‐to‐sample task as an animal model of dementia

“…In terms of performance enhancement, d-cycloserine, a compound active at the glycine recognition site on the NMDA receptor, has recently been shown to be active in enhancing learning [Monahan et al, 19891. The NMDA/glutamate system may be compromised in AD [Cotman et al, 1989;Cross et al, 1987;Greenamyre et al, 1985;Hardy et al, 1987;Hyman et al, 19871. These considerations suggest that decrements in NMDA receptor function, as shown by DNMTS or similar protocols, may be useful in the research for antidementia compounds.…”

Effects of Probiotic Supplementation on Exercise and the Underlying Mechanisms

“…For example, Savignac et al showed that B. longum 1714 administration exerted a positive impact on cognition in an anxious mouse strain [118]. Additionally, Cotman et al found that exercise also improves learning memory function by regulating the levels of learning memory-related molecules such as N-methyl-D-aspartate receptors and brain-derived neurotrophic factors in the brain [119]. Although more studies in this area are needed, the evidence available indicates that exercise may affect brain behavior through the GBA.…”