Whole brain mapping of glutamate distribution in adult and old primates at 11.7T

Garin, Clément M.; Nadkarni, Nachiket A.; Pépin, Jérémy; Flament, Julien; Dhénain, Marc

doi:10.1016/j.neuroimage.2022.118984

Cited by 5 publications

(4 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The majority of GluCEST studies, however, have focused on preclinical aging and disease models. Aging reduced GluCEST contrast in multiple networks associated with cognition in mouse lemur primates ( Garin et al, 2022 ). Decreased hippocampal glutamate has also been observed in 18+ month old amyloid ( Haris et al, 2013 ) and tau ( Crescenzi et al, 2014 ) mouse models of AD similar to observations using implantable biosensors.…”

Section: Diagnostic Methods For In Vivo Glutamate ...mentioning

confidence: 99%

Friend or Foe? Defining the Role of Glutamate in Aging and Alzheimer’s Disease

et al. 2022

View full text Add to dashboard Cite

Aging is a naturally occurring decline of physiological processes and biological pathways that affects both the structural and functional integrity of the body and brain. These physiological changes reduce motor skills, executive function, memory recall, and processing speeds. Aging is also a major risk factor for multiple neurodegenerative disorders including Alzheimer’s disease (AD). Identifying a biomarker, or biomarkers, that signals the transition from physiological to pathological aging would aid in earlier therapeutic options or interventional strategies. Considering the importance of glutamate signaling in synaptic plasticity, motor movement, and cognition, this neurotransmitter serves as a juncture between cognitive health and disease. This article discusses glutamatergic signaling during physiological aging and the pathological changes observed in AD patients. Findings from studies in mouse models of successful aging and AD are reviewed and provide a biological context for this transition. Finally, current techniques to monitor brain glutamate are highlighted. These techniques may aid in elucidating time-point specific therapeutic windows to modify disease outcome.

show abstract

Section: Diagnostic Methods For In Vivo Glutamate ...mentioning

confidence: 99%

Friend or Foe? Defining the Role of Glutamate in Aging and Alzheimer’s Disease

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In addition, beta-amyloid interrupts effective glutamate uptake by GLT-1 ( Conway, 2020 ), and microinjection of beta-amyloid fibrils into the hippocampal CA1 area of rats is associated with reduction in GLT-1 ( Wu et al, 2020 ). A recent study conducted chemical exchange saturation transfer imaging of glutamate (gluCEST) to characterize the distribution of the gluCEST contrast in the whole brain and in large-scale networks of mouse lemur primates as a model of Alzheimer’s disease ( Garin et al, 2022 ). This showed the detection of high gluCEST contrast in the nucleus accumbens, septum, basal forebrain, and cortical areas 24 and 25.…”

Section: Evidence That Hyperglutamatergic State Causes Neuroexcitotox...mentioning

confidence: 99%

“…Furthermore, the study was able to identify an age-related decrease in the gluCEST contrast in the nucleus accumbens, septum, basal forebrain, globus pallidus, hypophysis, cortical areas 24, 21, and 6, and in olfactory bulbs. An age-related gluCEST contrast decrease was also detected in specific neuronal networks such as fronto-temporal and evaluative limbic networks ( Garin et al, 2022 ).…”

Section: Evidence That Hyperglutamatergic State Causes Neuroexcitotox...mentioning

confidence: 99%

Ceftriaxone as a Novel Therapeutic Agent for Hyperglutamatergic States: Bridging the Gap Between Preclinical Results and Clinical Translation

Abulseoud

Alasmari²,

Hussein³

et al. 2022

Front. Neurosci.

View full text Add to dashboard Cite

Dysregulation of glutamate homeostasis is a well-established core feature of neuropsychiatric disorders. Extracellular glutamate concentration is regulated by glutamate transporter 1 (GLT-1). The discovery of a beta-lactam antibiotic, ceftriaxone (CEF), as a safe compound with unique ability to upregulate GLT-1 sparked the interest in testing its efficacy as a novel therapeutic agent in animal models of neuropsychiatric disorders with hyperglutamatergic states. Indeed, more than 100 preclinical studies have shown the efficacy of CEF in attenuating the behavioral manifestations of various hyperglutamatergic brain disorders such as ischemic stroke, amyotrophic lateral sclerosis (ALS), seizure, Huntington’s disease, and various aspects of drug use disorders. However, despite rich and promising preclinical data, only one large-scale clinical trial testing the efficacy of CEF in patients with ALS is reported. Unfortunately, in that study, there was no significant difference in survival between placebo- and CEF-treated patients. In this review, we discussed the translational potential of preclinical efficacy of CEF based on four different parameters: (1) initiation of CEF treatment in relation to induction of the hyperglutamatergic state, (2) onset of response in preclinical models in relation to onset of GLT-1 upregulation, (3) mechanisms of action of CEF on GLT-1 expression and function, and (4) non-GLT-1-mediated mechanisms for CEF. Our detailed review of the literature brings new insights into underlying molecular mechanisms correlating the preclinical efficacy of CEF. We concluded here that CEF may be clinically effective in selected cases in acute and transient hyperglutamatergic states such as early drug withdrawal conditions.

show abstract

“…Nowadays, CEST MRI has been applied to detecting various endogenous metabolites 3–6 and characterizing tissue microenvironments 7,8 . Numerous studies have demonstrated that CEST MRI can provide valuable information for the assessment of various diseases, including cerebral ischemia, neurological disorders, and solid tumors 8–11 . However, due to limited spectral separation and competing effects (e.g., the scaled‐down effect from magnetization transfer contrast and spillover from direct water saturation), 12,13 the clinical utilization of CEST MRI is still constrained by low CEST contrast and low signal‐to‐noise ratio (SNR) of acquired images, 14 which compromise its accuracy and reliability.…”

Section: Introductionmentioning

confidence: 99%

Boosting quantification accuracy of chemical exchange saturation transfer MRI with a spatial–spectral redundancy‐based denoising method

Chen,

Wu,

Yang

et al. 2023

NMR in Biomedicine

View full text Add to dashboard Cite

Chemical exchange saturation transfer (CEST) is a versatile technique that enables noninvasive detections of endogenous metabolites present in low concentrations in living tissue. However, CEST imaging suffers from an inherently low signal‐to‐noise ratio (SNR) due to the decreased water signal caused by the transfer of saturated spins. This limitation challenges the accuracy and reliability of quantification in CEST imaging. In this study, a novel spatial–spectral denoising method, called BOOST (suBspace denoising with nOnlocal lOw‐rank constraint and Spectral local‐smooThness regularization), was proposed to enhance the SNR of CEST images and boost quantification accuracy. More precisely, our method initially decomposes the noisy CEST images into a low‐dimensional subspace by leveraging the global spectral low‐rank prior. Subsequently, a spatial nonlocal self‐similarity prior is applied to the subspace‐based images. Simultaneously, the spectral local‐smoothness property of Z‐spectra is incorporated by imposing a weighted spectral total variation constraint. The efficiency and robustness of BOOST were validated in various scenarios, including numerical simulations and preclinical and clinical conditions, spanning magnetic field strengths from 3.0 to 11.7 T. The results demonstrated that BOOST outperforms state‐of‐the‐art algorithms in terms of noise elimination. As a cost‐effective and widely available post‐processing method, BOOST can be easily integrated into existing CEST protocols, consequently promoting accuracy and reliability in detecting subtle CEST effects.

show abstract

Whole brain mapping of glutamate distribution in adult and old primates at 11.7T

Cited by 5 publications

References 42 publications

Friend or Foe? Defining the Role of Glutamate in Aging and Alzheimer’s Disease

Friend or Foe? Defining the Role of Glutamate in Aging and Alzheimer’s Disease

Ceftriaxone as a Novel Therapeutic Agent for Hyperglutamatergic States: Bridging the Gap Between Preclinical Results and Clinical Translation

Boosting quantification accuracy of chemical exchange saturation transfer MRI with a spatial–spectral redundancy‐based denoising method

Contact Info

Product

Resources

About