PET imaging of metabolic changes after neural stem cells and GABA progenitor cells transplantation in a rat model of temporal lobe epilepsy

Du, Ruili; Wu, Shuang; Zhang, Xiaohui; He, Yang; Zhang, Kai; He, Xiao; Wang, Xiaoqun; Sun, Yujie; Wang, Qiangbin; Zhang, Hong; Tian, Mei

doi:10.1007/s00259-019-04408-2

Cited by 11 publications

(10 citation statements)

References 15 publications

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“…Positron emission tomography/computed tomography (PET/CT) is a new molecular imaging technique [19][20][21]. 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/CT imaging can estimate the state of glucose metabolism in tumors [22][23][24][25][26]. A high standard uptake value (SUVmax) has been shown to correlate with the malignancy of multiple tumors [27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of METTL3 associated with the metabolic status on ¹⁸F-FDG PET/CT in patients with Esophageal Carcinoma

et al. 2020

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Background: To investigate the expression of methyltransferase 3 (METTL3) and its relationship with 18 F-FDG uptake in patients with esophageal carcinoma (ESCA). Materials and methods:This study analyzed the expression of METTL3 in ESCA and its relationship with clinicopathological features by The Cancer Genome Atlas (TCGA) database. Immunohistochemical staining was performed on 57 tumor tissues of ESCA patients who underwent PET/CT scan before surgery to evaluate the expression of METTL3, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) in tumor tissues and peritumoral tissues. Analyze the relationship between SUVmax with METTL3, HK2, and GLUT1 expression. Results: The expression of METTL3, GLUT1, and HK2 was significantly increased in ESCA tissues compared with normal tissues (p < 0.001). The expression of METTL3 was correlated with tumor size and histological differentiation (p < 0.05), and there was no significant difference between age, sex, pathological types, tumor staging, or lymph node metastasis (p > 0.05). The SUVmax was significantly higher in tumors with high METTL3 expression (17.822±6.249) compared to low METTL3 expression (9.573±5.082) (p < 0.001). There was a positive correlation between the SUVmax and METTL3 expression in ESCA (r 2 = 0.647, p < 0.001). Multivariate analysis confirmed the association between SUVmax and METTL3 expression (p < 0.05). GLUT1 and HK2 expression in ESCA was positively correlated with 18 F-FDG uptake and METTL3 status (p < 0.001). Conclusions: The high expression of METTL3 is related to the high SUVmax in ESCA, and METTL3 may increase 18 F-FDG uptake by regulating GLUT1 and HK2.

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Section: Introductionmentioning

confidence: 99%

Overexpression of METTL3 associated with the metabolic status on ¹⁸F-FDG PET/CT in patients with Esophageal Carcinoma

et al. 2020

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“…We infer that neurometabolic decoupling might play a part in higher coupling. Previous studies have demonstrated that interictal discharges would result from an imbalance between neural excitatory and inhibitory activity 23 . Increased interictal glutamate levels also prove this point in mTLE‐HS patients 24 .…”

Section: Discussionmentioning

confidence: 83%

“…Previous studies have demonstrated that interictal discharges would result from an imbalance between neural excitatory and inhibitory activity. 23 Increased interictal glutamate levels also prove this point in mTLE-HS patients. 24 The astrocyte-neuron lactate shuttle makes a contribution to energy supply for neurons.…”

Section: Discussionmentioning

confidence: 94%

Altered coupling between resting‐state glucose metabolism and functional activity in epilepsy

Wang

Shan

Dai

et al. 2020

Ann Clin Transl Neurol

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Objective: Altered functional activities and hypometabolism have been found in medial temporal lobe epilepsy patients with hippocampal sclerosis (mTLE-HS). Hybrid PET/MR scanners provide opportunities to explore the relationship between resting-state energy consumption and functional activities, but whether repeated seizures disturb the bioenergetic coupling and its relationship with seizure outcomes remain unknown. Methods: 18 F-FDG PET and restingstate functional MRI (rs-fMRI) scans were performed with hybrid PET/MR in 26 patients with mTLE-HS and in healthy controls. Energy consumption was quantified by 18 F-FDG standardized uptake value ratio(SUVR) relative to cerebellum. Spontaneous neural activities were estimated using regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF) from rs-fMRI. Between-group differences in SUVR and rs-fMRI derived metrics were evaluated by two-sample t test. Voxel-wise spatial correlations were explored between SUVR and ReHo, fALFF across gray matter and compared between groups. Furthermore, the relationships between altered fALFF/SUVR and ReHo/ SUVR coupling and surgical outcomes were evaluated. Results: Both the patients and healthy controls showed significant positive correlations between SUVR and rs-fMRI metrics. Spatial correlations between SUVR and fMRIderived metrics across gray matter were significantly higher in patients with mTLE-HS compared with healthy controls (fALFF/SUVR, P < 0.001; ReHo/ SUVR, P = 0.022). Higher fALFF/SUVR couplings were found in patients who had Engel class IA after surgery than all other (P = 0.025), while altered ReHo/ SUVR couplings (P = 0.097) were not. Conclusion: These findings demonstrated altered bioenergetic coupling across gray matter and its relationship with seizure outcomes, which may provide novel insights into pathogenesis of mTLE-HS and potential biomarkers for epilepsy surgery planning.

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“…PET images and CT images were co-registered by PMOD software (version 3.902, PMOD Technologies Ltd.) ( 51 ). PMOD kinetic modeling tool (PKIN) was used to perform kinetic analysis.…”

Section: Methodsmentioning

confidence: 99%

Mitolysosome exocytosis, a mitophagy-independent mitochondrial quality control in flunarizine-induced parkinsonism-like symptoms

Bao

Zhou

et al. 2022

Sci. Adv.

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Mitochondrial quality control plays an important role in maintaining mitochondrial homeostasis and function. Disruption of mitochondrial quality control degrades brain function. We found that flunarizine (FNZ), a drug whose chronic use causes parkinsonism, led to a parkinsonism-like motor dysfunction in mice. FNZ induced mitochondrial dysfunction and decreased mitochondrial mass specifically in the brain. FNZ decreased mitochondrial content in both neurons and astrocytes, without affecting the number of nigral dopaminergic neurons. In human neural progenitor cells, FNZ also induced mitochondrial depletion. Mechanistically, independent of ATG5- or RAB9-mediated mitophagy, mitochondria were engulfed by lysosomes, followed by a vesicle-associated membrane protein 2– and syntaxin-4–dependent extracellular secretion. A genome-wide CRISPR knockout screen identified genes required for FNZ-induced mitochondrial elimination. These results reveal not only a previously unidentified lysosome-associated exocytosis process of mitochondrial quality control that may participate in the FNZ-induced parkinsonism but also a drug-based method for generating mitochondria-depleted mammal cells.

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PET imaging of metabolic changes after neural stem cells and GABA progenitor cells transplantation in a rat model of temporal lobe epilepsy

Cited by 11 publications

References 15 publications

Overexpression of METTL3 associated with the metabolic status on ¹⁸F-FDG PET/CT in patients with Esophageal Carcinoma

Overexpression of METTL3 associated with the metabolic status on ¹⁸F-FDG PET/CT in patients with Esophageal Carcinoma

Altered coupling between resting‐state glucose metabolism and functional activity in epilepsy

Mitolysosome exocytosis, a mitophagy-independent mitochondrial quality control in flunarizine-induced parkinsonism-like symptoms

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PET imaging of metabolic changes after neural stem cells and GABA progenitor cells transplantation in a rat model of temporal lobe epilepsy

Cited by 11 publications

References 15 publications

Overexpression of METTL3 associated with the metabolic status on 18F-FDG PET/CT in patients with Esophageal Carcinoma

Overexpression of METTL3 associated with the metabolic status on 18F-FDG PET/CT in patients with Esophageal Carcinoma

Altered coupling between resting‐state glucose metabolism and functional activity in epilepsy

Mitolysosome exocytosis, a mitophagy-independent mitochondrial quality control in flunarizine-induced parkinsonism-like symptoms

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Overexpression of METTL3 associated with the metabolic status on ¹⁸F-FDG PET/CT in patients with Esophageal Carcinoma

Overexpression of METTL3 associated with the metabolic status on ¹⁸F-FDG PET/CT in patients with Esophageal Carcinoma