Non-invasive characterization of amyotrophic lateral sclerosis in a hTDP-43A315T mouse model: A PET-MR study

Weerasekera, Akila; Crabbé, Melissa; Tomé, Sandra O.; Gsell, Willy; Sima, Diana M.; Casteels, Cindy; Dresselaers, Tom; Deroose, Christophe M.; Huffel, Sabine Van; Thal, Dietmar Rudolf; Damme, Philip Van

doi:10.1016/j.nicl.2020.102327

Cited by 10 publications

(7 citation statements)

References 54 publications

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“…In the spinal cord, glucose metabolism appeared to be reduced at early symptomatic and end stages of the disease in SOD1 G93A mice, but was increased before disease onset [96]. Recently, Weerasekera et al used simultaneous 18 F-FDG PETmagnetic resonance imaging and showed that glucose metabolism is decreased in the motor and somatosensory cortices of TDP-43 A315T mice while it was increased in midbrain region between 3 and 7 months of age, as compared to WT controls [97]. This suggests that similar changes in glucose metabolism may be observed across ALS disease models.…”

Section: Alterations In Glucose Transport or Utilizationmentioning

confidence: 99%

CNS glucose metabolism in Amyotrophic Lateral Sclerosis: a therapeutic target?

et al. 2021

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Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder primarily characterized by selective degeneration of both the upper motor neurons in the brain and lower motor neurons in the brain stem and the spinal cord. The exact mechanism for the selective death of neurons is unknown. A growing body of evidence demonstrates abnormalities in energy metabolism at the cellular and whole-body level in animal models and in people living with ALS. Many patients with ALS exhibit metabolic changes such as hypermetabolism and body weight loss. Despite these whole-body metabolic changes being observed in patients with ALS, the origin of metabolic dysregulation remains to be fully elucidated. A number of pre-clinical studies indicate that underlying bioenergetic impairments at the cellular level may contribute to metabolic dysfunctions in ALS. In particular, defects in CNS glucose transport and metabolism appear to lead to reduced mitochondrial energy generation and increased oxidative stress, which seem to contribute to disease progression in ALS. Here, we review the current knowledge and understanding regarding dysfunctions in CNS glucose metabolism in ALS focusing on metabolic impairments in glucose transport, glycolysis, pentose phosphate pathway, TCA cycle and oxidative phosphorylation. We also summarize disturbances found in glycogen metabolism and neuroglial metabolic interactions. Finally, we discuss options for future investigations into how metabolic impairments can be modified to slow disease progression in ALS. These investigations are imperative for understanding the underlying causes of metabolic dysfunction and subsequent neurodegeneration, and to also reveal new therapeutic strategies in ALS.

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Section: Alterations In Glucose Transport or Utilizationmentioning

confidence: 99%

CNS glucose metabolism in Amyotrophic Lateral Sclerosis: a therapeutic target?

et al. 2021

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“…A similar observation was previously described by Miyazaki et al [ 38 ], who showed that in the spinal cord of SOD1-G93A mice, glucose metabolism appeared to be reduced at early symptomatic and end stages of the disease but was increased before disease onset. Recently, another study used simultaneous [ 18 F]-FDG PET magnetic resonance imaging and showed that glucose metabolism is decreased in the motor and somatosensory cortices of TDP-43 (A315T) mice, while at the same time, it was increased in the midbrain region between at pre-symptomatic age, as compared to WT controls [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Swim Training Ameliorates Hyperlocomotion of ALS Mice and Increases Glutathione Peroxidase Activity in the Spinal Cord

Dzik

Flis

Bytowska

et al. 2021

IJMS

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(1) Background: Amyotrophic lateral sclerosis (ALS) is an incurable, neurodegenerative disease. In some cases, ALS causes behavioral disturbances and cognitive dysfunction. Swimming has revealed a neuroprotective influence on the motor neurons in ALS. (2) Methods: In the present study, a SOD1-G93A mice model of ALS were used, with wild-type B6SJL mice as controls. ALS mice were analyzed before ALS onset (10th week of life), at ALS 1 onset (first symptoms of the disease, ALS 1 onset, and ALS 1 onset SWIM), and at terminal ALS (last stage of the disease, ALS TER, and ALS TER SWIM), and compared with wild-type mice. Swim training was applied 5 times per week for 30 min. All mice underwent behavioral tests. The spinal cord was analyzed for the enzyme activities and oxidative stress markers. (3) Results: Pre-symptomatic ALS mice showed increased locomotor activity versus control mice; the swim training reduced these symptoms. The metabolic changes in the spinal cord were present at the pre-symptomatic stage of the disease with a shift towards glycolytic processes at the terminal stage of ALS. Swim training caused an adaptation, resulting in higher glutathione peroxidase (GPx) and protection against oxidative stress. (4) Conclusion: Therapeutic aquatic activity might slow down the progression of ALS.

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“…The effects of ALS on metabolic function in humans and animal models of ALS are yet to be fully understood. In animals, one study has measured the glucose uptake in the brains of mice carrying the human TDP-43 A315T mutation [4]. The authors observed a significant hypometabolism in motor and somatosensory cortex, as well as a hypermetabolism in amygdala and brainstem.…”

Section: Main Textmentioning

confidence: 99%