Cortical NMDA Receptor Properties and Membrane Fluidity Are Altered in Alzheimer's Disease

Abstract

NMDA receptor density as measured by the specific binding of [³H]MK 801 was significantly decreased (about 20%) in the frontal but not in the parietal cortex of postmortem brain samples of Alzheimer''s disease (AD) patients (n = 21), when compared with control brains (n = 20). Membrane fluidity was not altered in the frontal cortex samples, but was slightly reduced in the parietal cortex samples of the AD patients. Since AD-specific histopathological changes (densities of senile plaques and neurofibrillary tangles) were about similar in both areas, it is concluded that the reductions of NMDA receptor densities in the frontal cortex is independent of AD-specific histopathological changes and of changes of membrane fluidity.

Cholesterol Modulates the Membrane- Disordering Effects of Beta-Amyloid Peptides in the Hippocampus: Specific Changes in Alzheimer’s Disease

“…Our findings of distinct alterations in the hydrocarbon core of hippocampal AD membranes, as revealed by steady-state anisotropy, are in line with various other findings, usually reporting reduced brain membrane fluidity using the probe DPH [16,17,19], although Zubenko [20] found no significant alterations in the Fig. 3.…”

“…It has been assumed that this effect of Aß on membrane properties may be part of a cascade of events finally leading to neurodegenerative alterations occurring during AD. If this is the case, this specific effect of Aß should not be altered in AD brains, even though several changes in membrane Dement Geriatr Cogn Disord 2000; 11:181-186 Eckert/Cairns/Maras/Gattaz/Müller physical properties have been reported in post-mortem AD brain tissues [16][17][18][19][20]. At the biochemical level, these membrane alterations include changes in phospholipid composition [21][22][23][24], as well as in the concentration and distribution of membrane-bound cholesterol [18].…”

Dissociating β-Amyloid from α7 Nicotinic Acetylcholine Receptor by a Novel Therapeutic Agent, S 24795, Normalizes α7 Nicotinic Acetylcholine and NMDA Receptor Function in Alzheimer's Disease Brain

“…Since reducing A␤ 42 -␣7nAChR complexes (S 24795) or blocking A␤ 42 -␣7nAChR interaction (A␤ 12-28 ) attenuates A␤ 42 deleterious effects on ␣7nAChRs and NMDARs, removing A␤ 42 from ␣7nAChRs may improve synaptic function regulated by ␣7nAChRs and NMDARs. Nevertheless, protracted A␤ exposure in AD eventually causes synaptic loss (Hsieh et al, 2006;Shankar et al, 2007) and reduces ␣7nAChR and NMDAR function and density (Scheuer et al, 1996;Wevers et al, 1999). This synaptic loss is reflected by a weaker reversal of ␣7nAChR and NMDAR function in AD versus A␤ 42 -exposed controls and the failure of S 24795 to rescue the reduced K ϩ depolarization-induced Ca 2ϩ influx in AD brain tissues.…”

Effect of latent iron deficiency on GABA and glutamate neuroreceptors in rat brain

“…The mechanism by which iron deficiency changes the binding affinity is unclear. Fluidity of the biological membranes can influence the interaction particularly under in vivo conditions (29). The increase in GABA but decrease in glutamate receptor can explain the effects on higher mental functions reported in humans (7,30).…”