The N-methyl-d-aspartate receptor complex in Alzheimer's disease: reduced regulation by glycine but not zinc

Steele, Janet; Palmer, Alan M.; Stratmann, Gary C.; Bowen, David M.

doi:10.1016/0006-8993(89)90333-8

Cited by 39 publications

(13 citation statements)

References 33 publications

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“…aSignificantly different from corresponding value obtained in the absence of 30 ~tM glycine (p < 0.001, paired t-test) a covariate in the ANOVA. Zinc inhibited [-3H]dizocilpine binding in a dosedependent fashion, as previously reported in human brain (Steele et al, 1989). Zn 2 + ICs0 values were not significantly different in control and suicide brains in both frontal cortex and parietal cortex (Table 1).…”

Section: Resultssupporting

confidence: 75%

“…[3H]dizocilpine binding in the presence of 100gM glutamate was significantly enhanced by co-incubation with 30 gM glycine in both areas of cortex examined (Table 1), as has been demonstrated previously in human brain (Procter et al, 1989;Steele et al, 1989). However, neither binding in the presence of glutamate or glutamate plus glycine was different in control (n = 8) and suicide subjects (n = 6) in either frontal cortex or parietal cortex (Table 1).…”

Section: Resultssupporting

confidence: 68%

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Similar effects of glycine, zinc and an oxidizing agent on [3H]dizocilpine binding to the N-methyl-D-aspartate receptor in neocortical tissue from suicide victims and controls

Palmer

Burns

Arango

et al. 1994

J. Neural Transmission

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This study used [3H]dizocilpine (MK-801) binding to the N-methyl-D-aspartate (NMDA) receptor to examine glycine, redox and zinc modulatory sites in membranes derived from the frontal and parietal cortex of control subjects (n = 8) and suicide victims (n = 6). [3H]dizocilpine binding in the presence of glutamate and glutamate plus glycine was similar in control and suicide subjects. The sulphydryl redox site was assessed using the oxidizing agent 5,5'-dithio-bis (2-nitrobenzoic acid), which inhibited binding in a dose-dependent fashion. Both redox and zinc sites were unaffected in the frontal and parietal cortex of suicide victims. These data indicate that the NMDA receptor and its glycine, redox and zinc subsites are preserved in the neocortex of suicide victims.

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Section: Resultssupporting

confidence: 75%

Section: Resultssupporting

confidence: 68%

Similar effects of glycine, zinc and an oxidizing agent on [3H]dizocilpine binding to the N-methyl-D-aspartate receptor in neocortical tissue from suicide victims and controls

Palmer

Burns

Arango

et al. 1994

J. Neural Transmission

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“…If a decline in receptor binding sites does not underlie reduced maze learning in aged F344 rats, then other mechanisms would have to be considered. Impaired glycine or polyamine modulation of the NMDA receptor might be involved in reducing signal transduction through this receptor; 46,47 however, we have directed attention to other signal transduction events that possibly underlie the deficient learning observed in aged rats. Specifically, we have focused on NO involvement in maze learning.…”

Section: Glutamate Hypothesismentioning

confidence: 99%

Age‐associated Memory Impairment: Assessing the Role of Nitric Oxide

Meyer¹,

Spangler²,

Kametani³

et al. 1998

Annals of the New York Academy of Sciences

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Several neurotransmitter systems have been investigated to assess hypothesized mechanisms underlying the decline in recent memory abilities in normal aging and in Alzheimer's disease. Examining the performance of F344 rats in a 14-unit T-maze (Stone maze), we have focused on the muscarinic cholinergic (mACh) and the N-methyl-D-aspartate (NMDA) glutamate (Glu) systems and their interactions. Maze learning is impaired by antagonists to mACh or NMDA receptors. We have also shown that stimulation of mACh receptors can overcome a maze learning deficit induced by NMDA blockade, and stimulation of the NMDA receptor can overcome a similar blockade of mACh receptors. No consistent evidence in rats has been produced from our laboratory to reveal significant age-related declines in mACh or NMDA receptor binding in the hippocampus (HC), a brain region that is greatly involved in processing of recent memory. Thus, we have directed attention to the possibility of a common signal transduction pathway, the nitric oxide (NO) system. Activated by calcium influx through the NMDA receptor, NO is hypothesized to be a retrograde messenger that enhances presynaptic Glu release. Maze learning can be impaired by inhibiting the synthetic enzyme for NO, nitric oxide synthase (NOS), or enhanced by stimulating NO release. However, we have found no age-related loss of NOS-containing HC neurons or fibers in rats. Additionally, other laboratories have reported no evidence of an age-related loss of HC NOS activity. In a microdialysis study we have found preliminary evidence of reduced NO production following NMDA stimulation. We are currently working to identify the parameters of this phenomenon as well as testing various strategies for safely stimulating the NO system to improve memory function in aged rats.

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“…These factors can complicate comparisons of receptors between disease groups and control patients and information regarding their influence on the NMDA receptor and its response to modulation is essential in evaluating postmortem data in specific diseases. Previous studies of the NMDA receptor and [3H]MK-801 binding in Alzheimer's disease are contradictory (Geddes et al, 1986: Mouradian et al, 1988Procter et al, 1989;Steele et al, 1989;Ninomiya et al, 1990), possibly due in some instances to insufficient regard for the influence of these factors. The present study was therefore initiated to examine the effect of gender, age, postmortem delay, agonal status, and storage time at -70°C on the binding of [3H]MK-801 in normal human cortex, and the modulation of this binding by glutamate, glycine, spermidine, and zinc, alone and in combination with each other.…”

mentioning

confidence: 99%

Examination of Parameters Influencing [³H]MK‐801 Binding in Postmortem Human Cortex

Piggott¹,

Perry²,

Sahgal³

et al. 1992

Journal of Neurochemistry

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[3H]MK-801 binding was used as an index of the glutamate receptor N-methyl-D-aspartate-subtype channel to examine the influence of gender, age, mode of death (agonal status), interval between death and autopsy (postmortem delay), and time in storage at -70 degrees C in well washed homogenate preparations from postmortem human frontal cortex. Basal binding and the modulatory effects of glutamate, glycine, spermidine, and zinc were examined with respect to these variables. Basal binding was sensitive to agonal status, being higher in sudden death cases. The effect of added glutamate and glycine was sensitive to age, with a trend toward lower binding with increasing age. The effect of added spermidine alone was sensitive to storage time at -70 degrees C, the binding being higher with longer storage time. The effect of added zinc was also sensitive to postmortem delay, with zinc causing a greater reduction in binding with shorter postmortem delays. Thus, with the exception of gender, all variables examined influenced [3H]MK-801 binding, highlighting the attention that should be given to these factors in postmortem studies in normal and diseased human subjects.

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The N-methyl-d-aspartate receptor complex in Alzheimer's disease: reduced regulation by glycine but not zinc

Cited by 39 publications

References 33 publications

Similar effects of glycine, zinc and an oxidizing agent on [3H]dizocilpine binding to the N-methyl-D-aspartate receptor in neocortical tissue from suicide victims and controls

Similar effects of glycine, zinc and an oxidizing agent on [3H]dizocilpine binding to the N-methyl-D-aspartate receptor in neocortical tissue from suicide victims and controls

Age‐associated Memory Impairment: Assessing the Role of Nitric Oxide

Examination of Parameters Influencing [³H]MK‐801 Binding in Postmortem Human Cortex

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The N-methyl-d-aspartate receptor complex in Alzheimer's disease: reduced regulation by glycine but not zinc

Cited by 39 publications

References 33 publications

Similar effects of glycine, zinc and an oxidizing agent on [3H]dizocilpine binding to the N-methyl-D-aspartate receptor in neocortical tissue from suicide victims and controls

Similar effects of glycine, zinc and an oxidizing agent on [3H]dizocilpine binding to the N-methyl-D-aspartate receptor in neocortical tissue from suicide victims and controls

Age‐associated Memory Impairment: Assessing the Role of Nitric Oxide

Examination of Parameters Influencing [3H]MK‐801 Binding in Postmortem Human Cortex

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Examination of Parameters Influencing [³H]MK‐801 Binding in Postmortem Human Cortex