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Hippocampus v.27 no.3, 2017년, pp.285 - 302   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Longitudinal imaging reveals subhippocampal dynamics in glutamate levels associated with histopathologic events in a mouse model of tauopathy and healthy mice

Crescenzi, Rachelle (Department of Biochemistry and Molecular Biophysics (BMB), University of Pennsylvania, Philadelphia, Pennsylvania ) ; DeBrosse, Catherine (Department of Biochemistry and Molecular Biophysics (BMB), University of Pennsylvania, Philadelphia, Pennsylvania ) ; Nanga, Ravi P. R. (Center for Magnetic Resonance and Optical Imaging (CMROI), University of Pennsylvania, Philadelphia, Pennsylvania ) ; Byrne, Matthew D. (Center for Neurodegenerative Disease Research (CNDR), University of Pennsylvania, Philadelphia, Pennsylvania ) ; Krishnamoorthy, Guruprasad (Center for Magnetic Resonance and Optical Imaging (CMROI), University of Pennsylvania, Philadelphia, Pennsylvania ) ; D'Aquilla, Kevin (Center for Magnetic Resonance and Optical Imaging (CMROI), University of Pennsylvania, Philadelphia, Pennsylvania ) ; Nath, Hari (Center for Magnetic Resonance and Optical Imaging (CMROI), University of Pe ) ; Morales, Knashawn H. ; Iba, Michiyo ; Hariharan, Hari ; Lee, Virginia M. Y. ; Detre, John A. ; Reddy, Ravinder ;
  • 초록  

    ABSTRACT Tauopathies are neurodegenerative disorders characterized by abnormal intracellular aggregates of tau protein, and include Alzheimer's disease, corticobasal degeneration, frontotemporal dementia, and traumatic brain injury. Glutamate metabolism is altered in neurodegenerative disorders manifesting in higher or lower concentrations of glutamate, its transporters or receptors. Previously, glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) demonstrated that glutamate levels are reduced in regions of synapse loss in the hippocampus of a mouse model of late‐stage tauopathy. We performed a longitudinal GluCEST imaging experiment paired with a cross‐sectional study of histologic markers of tauopathy to determine whether (1) early GluCEST changes are associated with synapse loss before volume loss occurs in the hippocampus, and whether (2) subhippocampal dynamics in GluCEST are associated with histopathologic events related to glutamate alterations in tauopathy. Live imaging of the hippocampus in three serial slices was performed without exogenous contrast agents, and subregions were segmented based on a k‐means cluster model. Subregions of the hippocampus were analyzed ( cornu ammonis CA1, CA3, dentate gyrus DG, and ventricle) in order to associate local MRI‐observable changes in glutamate with histological measures of glial cell proliferation (GFAP), synapse density (synaptophysin, VGlut1) and glutamate receptor (NMDA–NR1) levels. Early differences in GluCEST between healthy and tauopathy mice were measured in the CA1 and DG subregions (30% reduction, P ≤ 0.001). Synapse density was also significantly reduced in every subregion of the hippocampus in tauopathy mice by 6 months. Volume was not significantly reduced in any subregion until 13 months. Further, a gradient in glutamate levels was observed in vivo along hippocampal axes that became polarized as tauopathy progressed. Dynamics in hippocampal glutamate levels throughout lifetime were most closely correlated with combined changes in synaptophysin and GFAP, indicating that GluCEST imaging may be a surrogate marker of glutamate concentration in glial cells and at the synaptic level. ⓒ 2016 Wiley Periodicals, Inc.


  • 주제어

    tauopathy .   CEST .   synapse .   glutamate .   glia.  

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