Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic study
Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disease primarily characterized by progressive degeneration of motor neurons in the motor cortex, brainstem and spinal cord. Due to relatively fast progression of ALS, early diagnosis is essential for possible therapeutic interven...
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doaj-2dec229f303e493fb3207be09ab44cb32020-11-24T22:03:08ZengElsevierNeuroImage: Clinical2213-15822018-01-012010921105Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic studyA. Weerasekera0D.M. Sima1T. Dresselaers2S. Van Huffel3P. Van Damme4U. Himmelreich5Biomedical MRI Unit/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, BelgiumDepartment of Electrical Engineering (ESAT), STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven, Leuven, Belgium; icometrix, R&D department, Leuven, BelgiumRadiology, Department of Imaging and Pathology, UZ Leuven, Leuven, BelgiumDepartment of Electrical Engineering (ESAT), STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven, Leuven, BelgiumDepartment of Neurology, University Hospitals Leuven, Laboratory of Neurobiology, Leuven, Belgium; Department of Neurosciences, KU Leuven, Center for Brain & Disease Research, VIB, Leuven, BelgiumBiomedical MRI Unit/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium; Corresponding author at: Biomedical MRI Unit/MoSAIC, Department of Imaging and Pathology, KU Leuven, O&N 1 Herestraat 49 box 505, B-3000 Leuven, Belgium.Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disease primarily characterized by progressive degeneration of motor neurons in the motor cortex, brainstem and spinal cord. Due to relatively fast progression of ALS, early diagnosis is essential for possible therapeutic intervention and disease management. To identify potential diagnostic markers, we investigated age-dependent effects of disease onset and progression on regional neurochemistry in the SOD1G93A ALS mouse model using localized in vivo magnetic resonance spectroscopy (MRS). We focused mainly on the brainstem region since brainstem motor nuclei are the primarily affected regions in SOD1G93A mice and ALS patients. In addition, metabolite profiles of the motor cortex were also assessed. In the brainstem, a gradual decrease in creatine levels were detected starting from the pre-symptomatic age of 70 days postpartum. During the early symptomatic phase (day 90), a significant increase in the levels of the inhibitory neurotransmitter γ- aminobutyric acid (GABA) was measured. At later time points, alterations in the form of decreased NAA, glutamate, glutamine and increased myo-inositol were observed. Also, decreased glutamate, NAA and increased taurine levels were seen at late stages in the motor cortex. A proof-of-concept (PoC) study was conducted to assess the effects of coconut oil supplementation in SODG93A mice. The PoC revealed that the coconut oil supplementation together with the regular diet delayed disease symptoms, enhanced motor performance, and prolonged survival in the SOD1G93A mouse model. Furthermore, MRS data showed stable metabolic profile at day 120 in the coconut oil diet group compared to the group receiving a standard diet without coconut oil supplementation. In addition, a positive correlation between survival and the neuronal marker NAA was found. To the best of our knowledge, this is the first study that reports metabolic changes in the brainstem using in vivo MRS and effects of coconut oil supplementation as a prophylactic treatment in SOD1G93A mice. Keywords: Amyotrophic lateral sclerosis, Magnetic resonance spectroscopy, SOD1G93A, Coconut oil, Brain metabolism, Creatinehttp://www.sciencedirect.com/science/article/pii/S2213158218302869 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
A. Weerasekera D.M. Sima T. Dresselaers S. Van Huffel P. Van Damme U. Himmelreich |
spellingShingle |
A. Weerasekera D.M. Sima T. Dresselaers S. Van Huffel P. Van Damme U. Himmelreich Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic study NeuroImage: Clinical |
author_facet |
A. Weerasekera D.M. Sima T. Dresselaers S. Van Huffel P. Van Damme U. Himmelreich |
author_sort |
A. Weerasekera |
title |
Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic study |
title_short |
Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic study |
title_full |
Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic study |
title_fullStr |
Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic study |
title_full_unstemmed |
Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic study |
title_sort |
non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the als sod1g93a mouse model: a 1h-magnetic resonance spectroscopic study |
publisher |
Elsevier |
series |
NeuroImage: Clinical |
issn |
2213-1582 |
publishDate |
2018-01-01 |
description |
Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disease primarily characterized by progressive degeneration of motor neurons in the motor cortex, brainstem and spinal cord. Due to relatively fast progression of ALS, early diagnosis is essential for possible therapeutic intervention and disease management. To identify potential diagnostic markers, we investigated age-dependent effects of disease onset and progression on regional neurochemistry in the SOD1G93A ALS mouse model using localized in vivo magnetic resonance spectroscopy (MRS). We focused mainly on the brainstem region since brainstem motor nuclei are the primarily affected regions in SOD1G93A mice and ALS patients. In addition, metabolite profiles of the motor cortex were also assessed. In the brainstem, a gradual decrease in creatine levels were detected starting from the pre-symptomatic age of 70 days postpartum. During the early symptomatic phase (day 90), a significant increase in the levels of the inhibitory neurotransmitter γ- aminobutyric acid (GABA) was measured. At later time points, alterations in the form of decreased NAA, glutamate, glutamine and increased myo-inositol were observed. Also, decreased glutamate, NAA and increased taurine levels were seen at late stages in the motor cortex. A proof-of-concept (PoC) study was conducted to assess the effects of coconut oil supplementation in SODG93A mice. The PoC revealed that the coconut oil supplementation together with the regular diet delayed disease symptoms, enhanced motor performance, and prolonged survival in the SOD1G93A mouse model. Furthermore, MRS data showed stable metabolic profile at day 120 in the coconut oil diet group compared to the group receiving a standard diet without coconut oil supplementation. In addition, a positive correlation between survival and the neuronal marker NAA was found. To the best of our knowledge, this is the first study that reports metabolic changes in the brainstem using in vivo MRS and effects of coconut oil supplementation as a prophylactic treatment in SOD1G93A mice. Keywords: Amyotrophic lateral sclerosis, Magnetic resonance spectroscopy, SOD1G93A, Coconut oil, Brain metabolism, Creatine |
url |
http://www.sciencedirect.com/science/article/pii/S2213158218302869 |
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