1H-MRS Quantitation of Age-Dependent Taurine Changes in Mouse Brain

Zhu, Min; Akimana, Christine; Wang, Eugenia; Ng, Chin K.

doi:10.1007/s11307-019-01333-6

Cited by 11 publications

(6 citation statements)

References 30 publications

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“…Indeed, significant lower Tau concentrations were detected in the transgenic group with respect to WT at 15 and 18 months. These results are in line with previous findings as decreased Tau in the hippocampus of this model 33 , and decreased Tau/Cr ratio in AD patients 70 or aged animal models 71 . However, a recent study with the TgF344-AD model depicted increased cortical Tau levels at 18 months of age 32 .…”

Section: Discussionsupporting

confidence: 93%

Spatio-temporal metabolic rewiring in the brain of TgF344-AD rat model of Alzheimer’s disease

Muñoz‐Moreno

Simões

Tudela

et al. 2022

Sci Rep

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Brain damage associated with Alzheimer's disease (AD) occurs even decades before the symptomatic onset, raising the need to investigate its progression from prodromal stages. In this context, animal models that progressively display AD pathological hallmarks (e.g. TgF344-AD) become crucial. Translational technologies, such as magnetic resonance spectroscopy (MRS), enable the longitudinal metabolic characterization of this disease. However, an integrative approach is required to unravel the complex metabolic changes underlying AD progression, from early to advanced stages. TgF344-AD and wild-type (WT) rats were studied in vivo on a 7 Tesla MRI scanner, for longitudinal quantitative assessment of brain metabolic profile changes using MRS. Disease progression was investigated at 4 time points, from 9 to 18 months of age, and in 4 regions: cortex, hippocampus, striatum, and thalamus. Compared to WT, TgF344-AD rats replicated common findings in AD patients, including decreased N-acetylaspartate in the cortex, hippocampus and thalamus, and decreased glutamate in the thalamus and striatum. Different longitudinal evolution of metabolic concentration was observed between TgF344-AD and WT groups. Namely, age-dependent trajectories differed between groups for creatine in the cortex and thalamus and for taurine in cortex, with significant decreases in Tg344-AD animals; whereas myo-inositol in the thalamus and striatum showed greater increase along time in the WT group. Additional analysis revealed divergent intra- and inter-regional metabolic coupling in each group. Thus, in cortex, strong couplings of N-acetylaspartate and creatine with myo-inositol in WT, but with taurine in TgF344-AD rats were observed; whereas in the hippocampus, myo-inositol, taurine and choline compounds levels were highly correlated in WT but not in TgF344-AD animals. Furthermore, specific cortex-hippocampus-striatum metabolic crosstalks were found for taurine levels in the WT group but for myo-inositol levels in the TgF344-AD rats. With a systems biology perspective of metabolic changes in AD pathology, our results shed light into the complex spatio-temporal metabolic rewiring in this disease, reported here for the first time. Age- and tissue-dependent imbalances between myo-inositol, taurine and other metabolites, such as creatine, unveil their role in disease progression, while pointing to the inadequacy of the latter as an internal reference for quantification.

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Section: Discussionsupporting

confidence: 93%

Spatio-temporal metabolic rewiring in the brain of TgF344-AD rat model of Alzheimer’s disease

Muñoz‐Moreno

Simões

Tudela

et al. 2022

Sci Rep

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“…Detecting the taurine level of spleen tissue would help estimate the response to splenectomy postoperatively. Furthermore, the level of taurine of ITP can be detected by in vivo MRS, which can provide a useful indicator for predicting the response of ITP patients to splenectomy preoperatively, which may help identify the inappropriate candidates for splenectomy [23,24].…”

Section: Discussionmentioning

confidence: 99%

NMR-Based Metabolomics Identify Metabolic Change in Spleen of Idiopathic Thrombocytopenic Purpura Patients

Wang

Feng

et al. 2022

Metabolites

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Idiopathic thrombocytopenic purpura (ITP) is a common hematological disease and the abnormal platelet destruction in the spleen is a critical pathological mechanism for ITP. However, the metabolomic change in the spleen caused by ITP is still unclear. In the present study, the metabolomic information of 18 ITP and 20 normal spleen samples were detected by using 1H high-resolution magic angle spinning NMR spectroscopy (1H MAS NMR). Compared with normal spleen, the concentrations of acetate, alanine, glutamine, glycerol, isoleucine, lysine, valine, phenylalanine, leucine, and methanol in ITP spleen tissue were elevated and 3-hydroxybutyric acid, ascorbate, asparagine, ethanol, glycogen, low-density lipoprotein, malonate, myo-inositol, glycerophosphocholine, pyroglutamate, and taurine were decreased. Amino acids metabolic pathways, such as branched-chain amino acids pathway, were identified as the main involved pathways based on enrichment analysis. The decrease in taurine level in the spleen was the most obvious metabolic signature involving ITP with high sensitivity and specificity to distinguish the spleen of ITP from the normal (CI: 0.825–0.982). Notably, the level of taurine in the spleen was negatively correlated with the efficacy of splenectomy (r = 0.622, p = 0.006). Collectively, the data from our study revealed previously unknown ITP-related metabolomic changes in the spleen and found a potential diagnostic and efficacy-predictive biomarker for ITP treatment.

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“…N-acetyl-aspartate is a biomarker in the diagnosis of cognitive function in Alzheimer's patients [6] and anxiety-related disorders in Parkinson's patients [5], while reduced concentrations are associated with aging [7] and memory deficits [8] in animal models. The higher concentrations of n-acetyl aspartate observed in the present study follow from the increased availability of the TCA cycle-derived acetyl-coA and carbon units from aspartate via oxaloacetate in Ket-fed mice.…”

Section: Discussionmentioning

confidence: 99%

“…The condensation of acetyl-CoA with aspartate produces n-acetyl aspartate, which is a biomarker associated with neuronal viability [4]. The relative abundance of n-acetyl aspartate, as determined by magnetic resonance spectroscopy, correlates with diminished anxiety-related outcomes in patients with neurological disease [5,6], while its presence in reduced concentrations correlates with advancing age [7] and memory deficits in mouse models [8].…”

Section: Introductionmentioning

confidence: 99%

A Dietary Ketone Ester Normalizes Abnormal Behavior in a Mouse Model of Alzheimer’s Disease

Pawlosky

Kashiwaya

King

et al. 2020

IJMS

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Because of a decreased sensitivity toward insulin, a key regulator of pyruvate dehydrogenase (PDH), Alzheimer’s patients have lower brain glucose utilization with reductions in Tricarboxylic Acid (TCA) cycle metabolites such as citrate, a precursor to n-acetyl-aspartate. In the 3xTgAd mouse model of Alzheimer’s disease (AD), aging mice also demonstrate low brain glucose metabolism. Ketone metabolism can overcome PDH inhibition and restore TCA cycle metabolites, thereby enhancing amino acid biosynthesis. A ketone ester of d-β-hydroxybutyrate was incorporated into a diet (Ket) and fed to 3xTgAd mice. A control group was fed a calorically matched diet (Cho). At 15 months of age, the exploratory and avoidance-related behavior patterns of the mice were evaluated. At 16.5 months of age, the animals were euthanized, and their hippocampi were analyzed for citrate, α-ketoglutarate, and amino acids. In the hippocampi of the Ket-fed mice, there were higher concentrations of citrate and α-ketoglutarate as well as higher concentrations of glutamate, aspartate and n-acetyl-aspartate compared with controls. There were positive associations between (1) concentrations of aspartate and n-acetyl-aspartate (n = 14, R = 0.9327), and (2) α-ketoglutarate and glutamate (n = 14, R = 0.8521) in animals maintained on either diet. Hippocampal n-acetyl-aspartate predicted the outcome of several exploratory and avoidance-related behaviors. Ketosis restored citrate and α-ketoglutarate in the hippocampi of aging mice. Higher concentrations of n-acetyl-aspartate corresponded with greater exploratory activity and reduced avoidance-related behavior.

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1H-MRS Quantitation of Age-Dependent Taurine Changes in Mouse Brain

Cited by 11 publications

References 30 publications

Spatio-temporal metabolic rewiring in the brain of TgF344-AD rat model of Alzheimer’s disease

Spatio-temporal metabolic rewiring in the brain of TgF344-AD rat model of Alzheimer’s disease

NMR-Based Metabolomics Identify Metabolic Change in Spleen of Idiopathic Thrombocytopenic Purpura Patients

A Dietary Ketone Ester Normalizes Abnormal Behavior in a Mouse Model of Alzheimer’s Disease

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