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Background: The imbalance of glutamate (Glu) and gamma-aminobutyric acid (GABA) neurotransmitter system plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Riluzole is a Glu modulator originally approved for amyotrophic lateral sclerosis that has shown potential neuroprotective effects in various neurodegenerative disorders. However, whether riluzole can improve Glu and GABA homeostasis in AD brain and its related mechanism of action remain unknown. This study utilized chemical exchange saturation transfer (CEST) imaging combined with proton magnetic resonance spectroscopy ( 1 H-MRS) to monitor the dynamic changes of Glu and GABA in riluzole-treated AD mice, aiming to evaluate the efficacy and mechanism of riluzole in AD treatment., Methods: GluCEST, GABACEST and 1 H-MRS were used to longitudinally monitor Glu and GABA levels in 3xTg AD mice treated with riluzole (12.5 mg/kg/day) or vehicle for 20 weeks. Magnetic resonance measurements were performed at baseline, 6, 12, and 20 weeks post-treatment. Cognitive performance was assessed using the Morris Water Maze (MWM) at baseline, 10, and 20 weeks. At the study endpoint, immunohistochemistry, Nissl staining, and Western blot were used to evaluate the brain pathology, neuronal survival, and protein expression., Results: GluCEST, GABACEST and 1 H-MRS consistently revealed higher levels of Glu and GABA in the brain of riluzole-treated AD mice compared to untreated controls, which were associated with improvements in spatial learning and memory. The cognitive improvements significantly correlated with the increased GluCEST signals and Glu levels. Immunohistochemistry and Nissl staining demonstrated that riluzole treatment reduced amyloid-beta (Aβ) deposition, tau hyperphosphorylation, GFAP-positive astrocyte activation, and prevented neuronal loss. Moreover, riluzole upregulated the expression of excitatory amino acid transporter 2 (EAAT2), glutamic acid decarboxylase 65/67 (GAD65/67), and glutamine synthetase (GS), suggesting enhanced neurotransmitter metabolism., Conclusions: CEST imaging combined with 1 H-MRS demonstrated the effectiveness of riluzole in modulating Glu- and GABA-related changes and improving cognitive function in 3xTg AD mice, potentially through regulating key proteins involved in neurotransmitter metabolism. These findings suggest riluzole as a therapeutic agent for Alzheimer's disease and highlight the utility of multimodal MR imaging in monitoring treatment response and exploring disease mechanisms., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were approved by the Ethics Committee of Shantou University Medical College (Approval ID: SUMC2022-597) and conducted in accordance with ARRIVE guidelines. Consent of publication: All authors have read and agreed with the publication of the manuscript in its current form. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Early life stress (ELS) is associated with an increased risk of developing depression and anxiety disorders. Disturbances of the neurobiological glutamatergic system are implicated in depression; however, the long-term effects of ELS on glutamate (Glu) metabolites remain unclear. Our study used 7T proton magnetic resonance spectroscopy (7T 1 H MRS) to detect metabolic Glu in a rat model to investigate maternal deprivation (MD)-induced ELS. MD was established in Sprague-Dawley rats by periodic separation from mothers and peers. Changes in the hippocampal volume and Glu metabolism were detected by 7T 1 H MRS after testing for depression-like behavior via open field, sucrose preference, and Morris water maze tests. Adult MD offspring exhibited depression-like behavior. Compared to the control, the MD group exhibited reduced ratio of central activity time to total time and decreased sucrose consumption ( p < 0.05). MD rats spent less time in the fourth quadrant, where the platform was originally placed, in the Morris water maze test. According to 7T 1 H MRS, hippocampus of MD rats had elevated Glu and glutamate + glutamine (Glu+Gln) levels compared with the control group hippocampi, but Gln, γ-aminobutyric acid (GABA), and glutamate + glutamine (Glu+Gln) in the prefrontal cortex of MD rats showed a downward trend. Depression-like behavior and cognition deficits related to ELS may induce region-specific changes in Glu metabolism in the prefrontal cortex and hippocampus. The novel, noninvasive 7T 1 H MRS-identified associations between Glu levels and ELS may guide future clinical studies.

Glutamate excitoxicity plays a crucial role in the pathophysiology of traumatic brain injury (TBI) through the initiation of secondary injuries. Glutamate chemical exchange saturation transfer (GluCEST) MRI is a newly developed technique to noninvasively image glutamate in vivo with high sensitivity and spatial resolution. The aim of the present study was to use a rat model of TBI to map changes in brain glutamate distribution and explore the capability of GluCEST imaging for detecting secondary injuries. Sequential GluCEST imaging scans were performed in adult male Sprague-Dawley rats before TBI and at 1, 3, 7, and 14 days after TBI. GluCEST% increased and peaked on day 1 after TBI in the core lesion of injured cortex and peaked on day 3 in the ipsilateral hippocampus, as compared to baseline and controls. GluCEST% gradually declined to baseline by day 14 after TBI. A negative correlation between the GluCEST% of the ipsilateral hippocampus on day 3 and the time in the correct quadrant was observed in injured rats. Immunolabeling for glial fibrillary acidic protein showed significant astrocyte activation in the ipsilateral hippocampus of TBI rats. IL-6 and TNF-α in the core lesion peaked on day 1 postinjury, while those in the ipsilateral hippocampus peaked on day 3. These subsequently gradually declined to sham levels by day 14. It was concluded that GluCEST imaging has potential to be a novel neuroimaging approach for predicting cognitive outcome and to better understand neuroinflammation following TBI.

Copper is a trace element which exerts an important role in neuronal functions. Excessive Cu exposure is associated with central nervous system dysfunction, including memory loss. The present study examined the effects of CuCl2 exposure on the spatial learning and memory of rats, and on metabolites in the hippocampus. A total of 60 male Sprague‑Dawley rats (10 rats/group) were intraperitoneally injected with various doses (0, 0.5, 1.0, 2.0, 4.0 and 6.0 mg/kg) of CuCl2 three times every other day for 6 days. Rats administered with 1.0 ml/kg sterile saline were used as controls. A total of 2 days subsequent to the final injection, the rats were subjected to the Morris water maze (MWM) test, followed by proton magnetic resonance spectroscopy (1H‑MRS). The rats were subsequently sacrificed, and their hippocampal tissues were processed for high performance liquid chromatography (HPLC). The MWM test demonstrated that the high‑dose groups exhibited worse spatial learning and memory compared with the controls; however, the rats that received a relatively low dose (2.0 mg/kg) exhibited a decreased impairment. The 1H‑MRS results revealed increased Glu, N‑acetyl‑L‑aspartate (NAA)+N‑acetylaspartylglutamate, phosphocreatine (PCr) and Cr+PCr levels in the hippocampus of the 2.0 mg/kg group. HPLC analysis revealed increased γ‑aminobutyric acid and glutamate (Glu) levels in the 2.0 mg/kg group, and decreased Glu levels in the 6.0 mg/kg group. The results of the present study demonstrated a beneficial effect of short‑term exposure to a relatively low dose of CuCl2 on spatial learning and memory, and the association of this effect with increased NAA and Glu levels in the hippocampus.

Social isolation (SI) rearing of rodents is a developmental manipulation, which is commonly compared with the psychological stressors in humans as it produces several behavioral outcomes similar to those observed in humans with early life stress. To explain the SI-induced behavioral outcomes, animal studies have been performed to examine the dopaminergic and glutamatergic systems in the brain. In this study, we measured possible changes in levels of glutamate and glutamine of SI-rats using proton magnetic resonance spectroscopy. We also assessed the oxidative stress parameters in certain brain regions to see if glutamate and/or glutamine changes, if any, are associated with oxidative stress. SI rearing for 8 weeks decreased the activities of antioxidant enzymes catalase, glutathione peroxidase, superoxide dismutase, and the total antioxidant capacity, but increased levels of hydrogen peroxide, in certain brain regions, of which prefrontal cortex and hippocampus were most vulnerable. It also decreased levels of glutamate, glutamine, N-acetyl-l-aspartate (NAA), and phosphocreatine in the dorsal hippocampus, but not in the cerebral cortex. Decreased phosphocreatine and NAA indicate energy metabolism deficit in brain cells; the latter also suggests the neuronal viability was inhibited. Decreased glutamate and glutamine may suggest the neuron-glial integrity was implicated by chronic SI. These neurochemical and biochemical changes may contribute to the SI-induced behavioral abnormalities including a high level of anxiety, social interaction deficit, and impaired spatial working memory shown in this study., (Copyright © 2015 Elsevier B.V. All rights reserved.)

FDG-PET and SPECT studies suggest that hypometabolism and hypoperfusion in occipital lobe and posterior cingulate gyrus (PCG) are prominent features of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), respectively. Cerebral blood flow and glucose metabolism are tightly linked to brain energy metabolism. 1H-MRS is a useful tool to directly detect energy metabolism. We aimed to use 1H-MRS to characterize metabolite concentrations in the occipital lobe and PCG in DLB and AD patients, and estimate their usefulness in the diagnosis of DLB. Nineteen DLB, 21 AD, and 18 normal control (NC) subjects underwent 1H-MRS with the voxels placed in bilateral occipital lobes and left PCG. The N-acetylaspartate (NAA) and glutamate (Glu) concentrations in occipital lobe in DLB were lower than those in AD and NC. Concentrations of these two metabolites in PCG in DLB were lower than those in NC, and were the same as those in AD. These results remained robust after correcting for relative gray matter volume in the region of interest. The NAA and Glu concentrations in occipital lobe in DLB were found correlated with global cognitive function. From the ROC curves with Glu concentrations in occipital lobe, the mean areas under the curve were 0.845 for the DLB/control (with sensitivity 83.3% and specificity 84.2%) and 0.773 for the DLB/AD (with sensitivity 66.7% and specificity 84.2%). Our study suggests that 1H-MRS investigation is valuable to detect the characteristic patterns of metabolite concentrations and is helpful in the diagnostic process and assessing dementia severity in DLB.

Background: The determination of tumor peripheral is of great significance in clinical diagnosis and treatment.Objective: In this study, we aim to obtain the metabolic condition in tumor peripheral of gliomas in vivo at 7T.Methods: C6 glioma cells were implanted into the right basal ganglia of Sprague-Dawley (SD) rats under stereotactic guided to create the glioma models. The models were sequentially undergone MRI and MRS examination on an 7T MR scanner designed for animals 7 days after the operation. Neuro metabolites were investigated from the center of the tumor, solid part of the tumor, peritumoral region, and contralateral white matter, and be quantified using the LCmodel software. Glial fibrillary acidic protein (GFAP) immunohistochemistry and conventional hematoxylin and eosin (HE) staining were performed after the imaging protocol.Results: Our results found that the inositol (Ins) and taurine (Tau) significantly defected in tumor peripheral compared to both tumor solid and normal tissues (P< 0.05). In contrast, the glutamate and glutamine (Glx) escalated and peaked at the tumor peripheral (P< 0.05).Conclusions: This study revealed that Ins, Tau, and Glx have the potential to provide specific biomarkers for the location of tumor peripheral of glioma. [ABSTRACT FROM AUTHOR]