Functional Deficits and Diffusion Tensor Magnetic Resonance Imaging of the Olfactory and Vision Systems in the Alzheimer’s Disease Model of Aging GluN3A Knockout Mice
5 affiliations
- 1Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322, USA
- 2Department of Neurology, Beijing Friendship Hospital, Beijing 100052, China
- 3Department of Neurology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
- 4Department of Chemistry, Advanced Translational Imaging Facility (ATIF), Georgia State University, Atlanta, GA 30303, USA
- 5Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA
Abstract
Sensory dysfunction, such as olfactory and visual deficits, is a notorious symptom during the progression of Alzheimer’s disease (AD) and related dementia (ADRD). The causal factor/s and structural disruptions underlying the sensory dysfunction in the AD/ADRD brain are not well understood. The NMDA receptor subunit GluN3A (NR3A) negatively regulates the receptor activity to uphold cellular Ca2+ homeostasis. In GluN3A knockout (KO) mice, animals spontaneously develop chronic neurodegenerative excitotoxicity, cognitive decline, and AD-like pathology. Using diffusion tensor imaging (DTI), we examined neuronal network destruction together with sensory dysfunction in the GluN3A KO mouse. Specific attention was given to the selective vulnerability of the olfactory and visual nuclei, white matter injury in regional connections between subcortical centers and the cortex and hippocampus. Compared to age-matched wild-type (WT) controls (male), consistent with our early reports in younger ages, 18-month-old aging/aged GluN3A KO mice (male) suffered significant olfactory, visual and social deficits, accompanied by marked Aβ42 deposition in the brain. Ex vivo MR images of the GluN3A KO and control brains were acquired on the 7T MRI system, using a four-channel mouse array RF coil. High-resolution 3D T2-weighted RARE anatomical and DTI scans were performed. The DTI analysis revealed that GluN3A KO mice developed brain atrophy, involving significant damage in the white and gray matter of the olfactory and visual systems and impaired pathways among the superior colliculus, lateral geniculate nucleus, and the hippocampus and/or the cortex. This investigation disclosed a receptor-mediated neurodegeneration that explains sensory syndromes featured in a sporadic AD mouse model.
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BibTeX
@article{wei2026functional,
title = {{Functional Deficits and Diffusion Tensor Magnetic Resonance Imaging of the Olfactory and Vision Systems in the Alzheimer’s Disease Model of Aging GluN3A Knockout Mice}},
author = {Ling Wei and Michael Qize Jiang and Yingying Zhao and Daiana Takashima and Yi Li and Khan Hekmatyar and Lingyue Wu and Ananth Sastry and Jenny J. Yang and Shan Ping Yu},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211951},
url = {https://www.mdpi.com/2073-4409/15/21/1951},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Functional Deficits and Diffusion Tensor Magnetic Resonance Imaging of the Olfactory and Vision Systems in the Alzheimer’s Disease Model of Aging GluN3A Knockout Mice
AU - Ling Wei
AU - Michael Qize Jiang
AU - Yingying Zhao
AU - Daiana Takashima
AU - Yi Li
AU - Khan Hekmatyar
AU - Lingyue Wu
AU - Ananth Sastry
AU - Jenny J. Yang
AU - Shan Ping Yu
PY - 2026
DA - 2026/10/27
JO - Cells
DO - 10.3390/cells15211951
UR - https://www.mdpi.com/2073-4409/15/21/1951
AB - Sensory dysfunction, such as olfactory and visual deficits, is a notorious symptom during the progression of Alzheimer’s disease (AD) and related dementia (ADRD). The causal factor/s and structural disruptions underlying the sensory dysfunction in the AD/ADRD brain are not well understood. The NMDA receptor subunit GluN3A (NR3A) negatively regulates the receptor activity to uphold cellular Ca2+ homeostasis. In GluN3A knockout (KO) mice, animals spontaneously develop chronic neurodegenerative excitotoxicity, cognitive decline, and AD-like pathology. Using diffusion tensor imaging (DTI), we examined neuronal network destruction together with sensory dysfunction in the GluN3A KO mouse. Specific attention was given to the selective vulnerability of the olfactory and visual nuclei, white matter injury in regional connections between subcortical centers and the cortex and hippocampus. Compared to age-matched wild-type (WT) controls (male), consistent with our early reports in younger ages, 18-month-old aging/aged GluN3A KO mice (male) suffered significant olfactory, visual and social deficits, accompanied by marked Aβ42 deposition in the brain. Ex vivo MR images of the GluN3A KO and control brains were acquired on the 7T MRI system, using a four-channel mouse array RF coil. High-resolution 3D T2-weighted RARE anatomical and DTI scans were performed. The DTI analysis revealed that GluN3A KO mice developed brain atrophy, involving significant damage in the white and gray matter of the olfactory and visual systems and impaired pathways among the superior colliculus, lateral geniculate nucleus, and the hippocampus and/or the cortex. This investigation disclosed a receptor-mediated neurodegeneration that explains sensory syndromes featured in a sporadic AD mouse model.
SN - 2073-4409
ER -