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Cited by 73Alzheimer's disease research and treatmentsAdvanced MRI Techniques and ApplicationsDementia and Cognitive Impairment Research

In vivo measurement of glutamate loss is associated with synapse loss in a mouse model of tauopathy

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Crescenzi, Rachelle, DeBrosse, Catherine, Nanga, Ravi Prakash Reddy, Reddy, Sanjana, Haris, Mohammed, Hariharan, Hari, Iba, Michiyo, Lee, Virginia M.Y. +3 more·2014·NeuroImage
DOI 10.1016/j.neuroimage.2014.06.067PMC PMC4303593
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Abstract

Glutamate is the primary excitatory neurotransmitter in the brain, and is implicated in neurodegenerative diseases such as Alzheimer's disease (AD) and several other tauopathies. The current method for measuring glutamate in vivo is proton magnetic resonance spectroscopy ((1)H MRS), although it has poor spatial resolution and weak sensitivity to glutamate changes. In this study, we sought to measure the effect of tau pathology on glutamate levels throughout the brain of a mouse model of tauopathy using a novel magnetic resonance imaging (MRI) technique. We employed glutamate chemical exchange saturation transfer (GluCEST) imaging, which has been previously validated as a complimentary method for measuring glutamate levels with several important advantages over conventional (1)H MRS. We hypothesized that the regional changes in glutamate levels would correlate with histological measurements of pathology including pathological tau, synapse and neuron loss. Imaging and spectroscopy were carried out on tau transgenic mice with the P301S mutation (PS19, n=9) and their wild-type littermates (WT, n=8), followed by immunohistochemistry of their brain tissue. GluCEST imaging resolution allowed for sub-hippocampal analysis of glutamate. Glutamate was significantly decreased by 29% in the CA sub-region of the PS19 hippocampus, and by 15% in the thalamus, where synapse loss was also measured. Glutamate levels and synapse density remained high in the dentate gyrus sub-region of the hippocampus, where neurogenesis is known to occur. The further development of GluCEST imaging for preclinical applications will be valuable, as therapies are being tested in mouse models of tauopathy.

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  • Past studies that reported synapse loss in PS19 mice relied on immunohistochemical staining of synaptic markers, which does not yield image resolution comparable to the methods employed here.

    “However, these studies relied on immunohistochemical staining of synaptic markers, which does not yield image resolution that is comparable to the methods employed here.”

    From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Crescenzi et al., 2014

    The Methods (§2.4) describe immunohistochemical staining for synaptophysin, a synaptic marker, and the Results (§3.3) report lower synapse density in the CA3 of PS19 mice. The paper does not compare the resolution of those staining images with the citing study’s methods; its Discussion compares GluCEST resolution with conventional ¹H MRS instead. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Synaptophysin, a presynaptic marker, was used for synapse quantification in two of the past studies.

    “Furthermore, synaptophysin, a presynaptic marker, was used for synapse quantification in two of the studies (Yoshiyama et al., 2007, Crescenzi et al., 2014), whereas our methods assess the postsynaptic dendritic spine.”

    From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Crescenzi et al., 2014

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Authors
Crescenzi, R., DeBrosse, C., Nanga, R. P. R., Reddy, S., Haris, M., Hariharan, H., Iba, M., Lee, V. M. Y., Detre, J. A., Borthakur, A., & Reddy, R.
Affiliations
University of Pennsylvania (US)
Corresponding author
Crescenzi, Rachelle
ORCID
Venue
NeuroImage
Publisher
Elsevier BV
Published
2014-11
Volume
101
Pages
185-192
ISSN
1053-8119 (ISSN-L)
DOI
10.1016/j.neuroimage.2014.06.067
PMC
PMC4303593
OpenAlex
W2092889411
Cited by
73
References
8
Citations by year
2026: 5 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 9 · 2017: 8 · 2016: 3 · 2015: 3 · 2014: 2
FWCI
3.32
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • NeuroImage (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIBIB (P41EB015893S1, P41EB015893)
  • NIDA (R21DA0332256-01)
  • NIA (P01AG17586)
  • Penn CTSA National Center for Research Resources (UL1RR024134)
  • National Center for Advancing Translational Sciences (UL1TR000003)
  • National Center for Research Resources
  • National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR000003)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
glutamate, tauopathy, synaptic loss, tau transgenic mice, hippocampus, thalamus, neurodegeneration, Alzheimer's disease, dentate gyrus, neurogenesis
MeSH terms
Animals, Disease Models, Animal, Hippocampus, Magnetic Resonance Imaging, Mice, Transgenic, Synapses, Thalamus, Glutamic Acid, Dentate Gyrus, Tauopathies, Mice, Neurogenesis, Proton Magnetic Resonance Spectroscopy

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