scholarly journals Quantitative Assessment of Occipital Metabolic and Energetic Changes in Parkinson’s Patients, Using In Vivo 31P MRS-Based Metabolic Imaging at 7T

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 145
Author(s):  
Xiao-Hong Zhu ◽  
Byeong-Yeul Lee ◽  
Paul Tuite ◽  
Lisa Coles ◽  
Abhishek G. Sathe ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Neurodegenerative Diseases ◽  
Intracellular Ph ◽  
Imaging Techniques ◽  
Neurological Deficits ◽  
Response To Treatment ◽  
Metabolic Imaging ◽  
Atp Production ◽  
31P Mrs

Abnormal energy metabolism associated with mitochondrial dysfunction is thought to be a major contributor to the progression of neurodegenerative diseases such as Parkinson’s disease (PD). Recent advancements in the field of magnetic resonance (MR) based metabolic imaging provide state-of-the-art technologies for non-invasively probing cerebral energy metabolism under various brain conditions. In this proof-of-principle clinical study, we employed quantitative 31P MR spectroscopy (MRS) imaging techniques to determine a constellation of metabolic and bioenergetic parameters, including cerebral adenosine triphosphate (ATP) and other phosphorous metabolite concentrations, intracellular pH and nicotinamide adenine dinucleotide (NAD) redox ratio, and ATP production rates in the occipital lobe of cognitive-normal PD patients, and then we compared them with age-sex matched healthy controls. Small but statistically significant differences in intracellular pH, NAD and ATP contents and ATPase enzyme activity between the two groups were detected, suggesting that subtle defects in energy metabolism and mitochondrial function are quantifiable before regional neurological deficits or pathogenesis begin to occur in these patients. Pilot data aiming to evaluate the bioenergetic effect of mitochondrial-protective bile acid, ursodeoxycholic acid (UDCA) were also obtained. These results collectively demonstrated that in vivo 31P MRS-based neuroimaging can non-invasively and quantitatively assess key metabolic-energetic metrics in the human brain. This provides an exciting opportunity to better understand neurodegenerative diseases, their progression and response to treatment.

scholarly journals News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 252
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Neurodegenerative Diseases ◽  
Imaging Techniques ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Specific Proteins ◽  
Great Relevance ◽  
The Brain ◽  
Positive Point

Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.

A FRET-based two-photon probe for in vivo tracking of pH during a traumatic brain injury process

2019 ◽  
Vol 43 (43) ◽  
pp. 17018-17022
Author(s):  
Baoping Zhai ◽  
Shuyang Zhai ◽  
Ruilin Hao ◽  
Jianjun Xu ◽  
Zhihong Liu
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurodegenerative Diseases ◽  
Intracellular Ph ◽  
Ph Change ◽  
Ph Probe ◽  
Two Photon ◽  
Ph Decrease

Traumatic brain injury (TBI) is a cause of neurodegenerative diseases accompanied by intracellular pH decrease. Herein, a FRET-based ratiometric two-photon fluorescent pH probe is designed to monitor pH change and understand TBI process.

[11C]Choline-PET imaging of breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1110-1110
Author(s):  
L. M. Kenny ◽  
R. C. Coombes ◽  
K. Contractor ◽  
J. Stebbing ◽  
A. Al-Nahhas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Imaging Modality ◽  
Imaging Techniques ◽  
Treatment Strategies ◽  
Breast Tumour ◽  
Response To Treatment ◽  
Choline Uptake ◽  
Choline Pet ◽  
Arterial Plasma

1110 Background: Molecular imaging techniques are increasingly being used in cancer diagnosis, staging, and assessment of response to treatment. This study sought to evaluate, for the first time, [11C]choline-PET in patients with breast cancer. The potential of [11C]choline-PET for differentiating tumours from normal tissue, correlation with molecular markers, determine its normal variability range, and finally the effect of trastuzumab on [11C]choline uptake in patients with breast cancer was investigated. Methods: 21 patients with newly diagnosed and recurrent breast cancer AJCC stage II-IV were enrolled in the study, all of whom had a baseline dynamic [11C]choline-PET scan with arterial sampling. 14 patients had 2 [11C]choline-PET scans to examine reproducibility, and 7 had a scan after trastuzumab. Analysis of [11C]choline uptake was measured using SUV, Ki (irreversible retention), and IRF@60min (retention using spectral analysis). Results: Breast tumour lesions were visualised by [11C]choline PET in all patients. The difference in tumour and non-tumour uptake were significant for SUV, Ki, and IRF@60 min (Wilcoxon p < 0.0001 for all parameters). [11C]choline uptake was reproducible in breast tumour lesions (r2 = 0.945 for SUV, 0.894 for Ki, and 0.799 for IRF60). The metabolism analysis of arterial plasma samples in 19 patients showed that [11C]choline decreased rapidly post-injection such that at 60 mins the mean radioactivity in arterial plasma due to choline was 15.15 ± 2.16%.Early responses to trastuzumab were determined to be significant in 5 lesions which corresponded with 3 clinical responses. Conclusions: [11C]choline-PET is a promising imaging modality in breast cancer, and could play an important role for determining response to novel treatment strategies in vivo. No significant financial relationships to disclose.

MUSCLE ENERGY METABOLISM IN MULTIPLE SCLEROSIS MEASURED BY IN VIVO 31P MRS 476

1997 ◽  
Vol 29 (Supplement) ◽  
pp. 83 ◽  
Author(s):  
P. -P. Z. Tang ◽  
A. T. White ◽  
S. Topaz ◽  
J. H. Petajan
Keyword(s):  
Multiple Sclerosis ◽  
Energy Metabolism ◽  
31P Mrs ◽  
Muscle Energy ◽  
Muscle Energy Metabolism

scholarly journals p53-inducible DPYSL4 associates with mitochondrial supercomplexes and regulates energy metabolism in adipocytes and cancer cells

2018 ◽  
Vol 115 (33) ◽  
pp. 8370-8375 ◽  
Author(s):  
Hidekazu Nagano ◽  
Naoko Hashimoto ◽  
Akitoshi Nakayama ◽  
Sawako Suzuki ◽  
Yui Miyabayashi ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Immunohistochemical Analysis ◽  
Cellular Functions ◽  
Atp Production ◽  
Chip Sequencing ◽  
Metastasis Models ◽  
Tumor Growth And Metastasis

The tumor suppressor p53 regulates multiple cellular functions, including energy metabolism. Metabolic deregulation is implicated in the pathogenesis of some cancers and in metabolic disorders and may result from the inactivation of p53 functions. Using RNA sequencing and ChIP sequencing of cancer cells and preadipocytes, we demonstrate that p53 modulates several metabolic processes via the transactivation of energy metabolism genes including dihydropyrimidinase-like 4 (DPYSL4). DPYSL4 is a member of the collapsin response mediator protein family, which is involved in cancer invasion and progression. Intriguingly, DPYSL4 overexpression in cancer cells and preadipocytes up-regulated ATP production and oxygen consumption, while DPYSL4 knockdown using siRNA or CRISPR/Cas9 down-regulated energy production. Furthermore, DPYSL4 was associated with mitochondrial supercomplexes, and deletion of its dihydropyrimidinase-like domain abolished its association and its ability to stimulate ATP production and suppress the cancer cell invasion. Mouse-xenograft and lung-metastasis models indicated that DPYSL4 expression compromised tumor growth and metastasis in vivo. Consistently, database analyses demonstrated that low DPYSL4 expression was significantly associated with poor survival of breast and ovarian cancers in accordance with its reduced expression in certain types of cancer tissues. Moreover, immunohistochemical analysis using the adipose tissue of obese patients revealed that DPYSL4 expression was positively correlated with INFg and body mass index in accordance with p53 activation. Together, these results suggest that DPYSL4 plays a key role in the tumor-suppressor function of p53 by regulating oxidative phosphorylation and the cellular energy supply via its association with mitochondrial supercomplexes, possibly linking to the pathophysiology of both cancer and obesity.

scholarly journals Effects of NKY-722, a novel calcium antagonist, on the changes of cardiac energy metabolism — an in vivo 31P-MRS study

1992 ◽  
Vol 58 ◽  
pp. 274
Author(s):  
Yuta Kobayashi ◽  
Youko Tanabe ◽  
Kazumasa Shinozuka ◽  
Shuji Takaori ◽  
Keisuke Hattori
Keyword(s):  
Calcium Antagonist ◽  
Energy Metabolism ◽  
31P Mrs ◽  
Cardiac Energy Metabolism ◽  
Cardiac Energy

scholarly journals Ca2+-Dependent Interaction of S100A1 with F1-ATPase Leads to an Increased ATP Content in Cardiomyocytes

2007 ◽  
Vol 27 (12) ◽  
pp. 4365-4373 ◽  
Author(s):  
Melanie Boerries ◽  
Patrick Most ◽  
Jonathan R. Gledhill ◽  
John E. Walker ◽  
Hugo A. Katus ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Atpase Activity ◽  
Cardiac Contractility ◽  
Gel Filtration ◽  
Dependent Manner ◽  
Atp Content ◽  
Atp Production ◽  
Rat Hearts

ABSTRACT S100A1, a Ca2+-sensing protein of the EF-hand family that is expressed predominantly in cardiac muscle, plays a pivotal role in cardiac contractility in vitro and in vivo. It has recently been demonstrated that by restoring Ca2+ homeostasis, S100A1 was able to rescue contractile dysfunction in failing rat hearts. Myocardial contractility is regulated not only by Ca2+ homeostasis but also by energy metabolism, in particular the production of ATP. Here, we report a novel interaction of S100A1 with mitochondrial F1-ATPase, which affects F1-ATPase activity and cellular ATP production. In particular, cardiomyocytes that overexpress S100A1 exhibited a higher ATP content than control cells, whereas knockdown of S100A1 expression decreased ATP levels. In pull-down experiments, we identified the α- and β-chain of F1-ATPase to interact with S100A1 in a Ca2+-dependent manner. The interaction was confirmed by colocalization studies of S100A1 and F1-ATPase and the analysis of the S100A1-F1-ATPase complex by gel filtration chromatography. The functional impact of this association is highlighted by an S100A1-mediated increase of F1-ATPase activity. Consistently, ATP synthase activity is reduced in cardiomyocytes from S100A1 knockout mice. Our data indicate that S100A1 might play a key role in cardiac energy metabolism.

Mitochondria and neuronal activity

2007 ◽  
Vol 292 (2) ◽  
pp. C641-C657 ◽  
Author(s):  
Oliver Kann ◽  
Richard Kovács
Keyword(s):  
Energy Metabolism ◽  
Neuronal Activity ◽  
Mitochondrial Function ◽  
Imaging Techniques ◽  
Neurological Diseases ◽  
Experimental Models ◽  
Metabolic Dysfunction ◽  
Membrane Excitability ◽  
Spatiotemporal Resolution ◽  
Atp Production

Mitochondria are central for various cellular processes that include ATP production, intracellular Ca2+ signaling, and generation of reactive oxygen species. Neurons critically depend on mitochondrial function to establish membrane excitability and to execute the complex processes of neurotransmission and plasticity. While much information about mitochondrial properties is available from studies on isolated mitochondria and dissociated cell cultures, less is known about mitochondrial function in intact neurons in brain tissue. However, a detailed description of the interactions between mitochondrial function, energy metabolism, and neuronal activity is crucial for the understanding of the complex physiological behavior of neurons, as well as the pathophysiology of various neurological diseases. The combination of new fluorescence imaging techniques, electrophysiology, and brain slice preparations provides a powerful tool to study mitochondrial function during neuronal activity, with high spatiotemporal resolution. This review summarizes recent findings on mitochondrial Ca2+ transport, mitochondrial membrane potential (ΔΨm), and energy metabolism during neuronal activity. We will first discuss interactions of these parameters for experimental stimulation conditions that can be related to the physiological range. We will then describe how mitochondrial and metabolic dysfunction develops during pathological neuronal activity, focusing on temporal lobe epilepsy and its experimental models. The aim is to illustrate that 1) the structure of the mitochondrial compartment is highly dynamic in neurons, 2) there is a fine-tuned coupling between neuronal activity and mitochondrial function, and 3) mitochondria are of central importance for the complex behavior of neurons.

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