Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.neurobiolaging.2007.03.014
Title: Alterations in NMDA receptor subunit densities and ligand binding to glycine recognition sites are associated with chronic anxiety in Alzheimer's disease
Authors: Tsang, Shirley WY 
Vinters, Harry V
Cummings, Jeffrey L
Wong, Peter T-H 
Chen, Christopher PL-H 
Lai, Mitchell KP 
Keywords: Science & Technology
Life Sciences & Biomedicine
Geriatrics & Gerontology
Neurosciences
Neurosciences & Neurology
Alzheimer's disease
glutamate receptors
glycine
neocortex
anxiety
D-ASPARTATE RECEPTORS
RAT-BRAIN
PHARMACOLOGICAL CHARACTERIZATION
AGGRESSIVE-BEHAVIOR
RADIOLIGAND BINDING
CHANNEL COMPLEX
NR1 SUBUNIT
AMINO-ACIDS
CORTEX
EXPRESSION
Issue Date: 1-Oct-2008
Publisher: ELSEVIER SCIENCE INC
Citation: Tsang, Shirley WY, Vinters, Harry V, Cummings, Jeffrey L, Wong, Peter T-H, Chen, Christopher PL-H, Lai, Mitchell KP (2008-10-01). Alterations in NMDA receptor subunit densities and ligand binding to glycine recognition sites are associated with chronic anxiety in Alzheimer's disease. NEUROBIOLOGY OF AGING 29 (10) : 1524-1532. ScholarBank@NUS Repository. https://doi.org/10.1016/j.neurobiolaging.2007.03.014
Abstract: Glutamatergic deficits are established neuropathological features of Alzheimer's disease (AD) and are known to correlate with cognitive impairments. In contrast, the role of glutamatergic alterations in behavioral and psychological symptoms of dementia (BPSD) is unclear. There is considerable preclinical evidence for the importance of glycine recognition sites (GlyRS) of N-methyl-d-aspartate (NMDA) receptors in the regulation of anxiety behaviors. This study aimed to correlate several glutamatergic measures with chronic anxiety in AD. Twenty-one AD patients assessed by the Neuropsychiatric Inventory (NPI) were divided into low anxiety (LA) and high anxiety (HA) subgroups. GlyRS and NMDA channel were measured by brain homogenate binding with [3H]MDL105,519 and [3H]MK-801, respectively. Densities of NMDA receptor NR2A, NR2B and alternate spliced NR1 subunits were quantified by immunoblotting. We found that the binding affinity to GlyRS was significantly higher in HA compared to LA, and this higher GlyRS affinity correlated with selective reduction of NR2A density as well as with elevated anxiety scores. Our observations suggest a novel mechanism whereby subunit specific changes in the NMDA receptor complex may be linked to chronic anxiety in AD via effects on GlyRS function. We propose that NR2A and GlyRS should be further assessed as novel targets of behavioral pharmacotherapy in AD. © 2007 Elsevier Inc. All rights reserved.
Source Title: NEUROBIOLOGY OF AGING
URI: https://scholarbank.nus.edu.sg/handle/10635/188381
ISSN: 01974580
15581497
DOI: 10.1016/j.neurobiolaging.2007.03.014
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