Dietary Vitamin D3 Restriction Exacerbates Disease Pathophysiology in the Spinal Cord of the G93A Mouse Model of Amyotrophic Lateral Sclerosis

Moghimi, Elnaz; Solomon, Jesse; Gianforcaro, Alexandro; Hamadeh, Mazen J.

doi:10.1371/journal.pone.0126355

Cited by 11 publications

(7 citation statements)

References 100 publications

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Section: Caffeine and Amyotrophic Lateral Sclerosismentioning

confidence: 99%

“…Pathological hallmarks of this disease include the following: progressive muscle weakness, atrophy, and spasticity . On a cellular level, excessive stimulation of glutamate receptors leads to a large influx of calcium ions into the postsynaptic neuron, resulting in oxidative stress, oxidative damage, inflammation, and apoptosis …”

Section: Caffeine and Amyotrophic Lateral Sclerosismentioning

confidence: 99%

“…Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease, characterized by degeneration of the upper and lower motor neurons, resulting in skeletal muscle atrophy and death by respiratory failure within 3-5 years of initial symptoms. [88][89][90] Pathological hallmarks of this disease include the following: progressive muscle weakness, atrophy, and spasticity. 91 On a cellular level, excessive stimulation of glutamate receptors leads to a large influx of calcium ions into the postsynaptic neuron, resulting in oxidative stress, oxidative damage, inflammation, and apoptosis.…”

Section: Caffeine and Amyotrophic Lateral Sclerosismentioning

confidence: 99%

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The neuroprotective effects of caffeine in neurodegenerative diseases

2017

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Caffeine is the most widely used psychostimulant in Western countries, with antioxidant, anti-inflammatory and anti-apoptotic properties. In Alzheimer's disease (AD), caffeine is beneficial in both men and women, in humans and animals. Similar effects of caffeine were observed in men with Parkinson's disease (PD); however, the effect of caffeine in female PD patients is controversial due to caffeine's competition with estrogen for the estrogen-metabolizing enzyme, CYP1A2. Studies conducted in animal models of amyotrophic lateral sclerosis (ALS) showed protective effects of A R antagonism. A study found caffeine to be associated with earlier age of onset of Huntington's disease (HD) at intakes >190 mg/d, but studies in animal models have found equivocal results. Caffeine is protective in AD and PD at dosages equivalent to 3-5 mg/kg. However, further research is needed to investigate the effects of caffeine on PD in women. As well, the effects of caffeine in ALS, HD and Machado-Joseph disease need to be further investigated. Caffeine's most salient mechanisms of action relevant to neurodegenerative diseases need to be further explored.

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Section: Caffeine and Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Section: Caffeine and Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Section: Caffeine and Amyotrophic Lateral Sclerosismentioning

confidence: 99%

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The neuroprotective effects of caffeine in neurodegenerative diseases

2017

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“…However, in in vivo studies, different results were reported. Although vitamin D supplementation seems to improve motor function in a well-known ALS mouse model (SOD1-G93A) ( 43 ), and vitamin D deficiency can exacerbate disease pathology ( 44 ), it can also promote deleterious effects in motor function and disease severity ( 45 , 46 ).…”

Section: Discussionmentioning

confidence: 99%

Is There a Role for Vitamin D in Amyotrophic Lateral Sclerosis? A Systematic Review and Meta-Analysis

et al. 2020

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Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive loss of motor neurons. Patients usually die 3-5 years after diagnosis from respiratory failure. Several studies investigated the role of vitamin D as a biomarker or a therapeutic option for ALS patients. To clarify the scientific evidence, we performed a systematic review and different meta-analyses regarding the potential role of vitamin D in ALS. Methods: We performed a systematic review of clinical trials, cohorts, and case-control studies retrieved from PubMed, EMBASE, and Cochrane databases reporting vitamin D levels as a putative biomarker for ALS diagnosis or prognosis or the effect of vitamin D supplementation in ALS patients. Whenever possible, data were pooled using a random-effects model, with an assessment of heterogeneity. Results: Out of 2,996 articles retrieved, we finally included 13 research articles, 12 observational studies (50% prospective), and 1 clinical trial. We found that ALS patients had slightly lower levels of vitamin D than controls (mean difference −6 ng/ml, 95% CI [−10.8; −1.3]), but important confounding factors were not considered in the studies analyzed. We found no relationship between vitamin D levels and ALS functional rate score-revised (ALSFRS-R), with highly heterogeneous results. Discordant results were reported in three studies regarding survival. Finally, five studies reported the effects of vitamin D supplementation with discordant results. Two of them showed a small improvement, whereas two others showed a deleterious effect on ALSFRS-R. One very small clinical trial with important methodological limitations showed some improvement in ALSFRS-R with high doses of vitamin D compared with normal doses. Conclusions: Our review did not find evidence to support the role of vitamin D on ALS diagnosis, prognosis, or treatment. Most studies had important limitations, mostly regarding the risk of bias for not considering confounding factors. Vitamin D supplementation should be offered to ALS patients to avoid other health issues related to vitamin D deficiency, but there is not enough evidence to support the use of vitamin D as a therapy for ALS.

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“…After blocking, another washing was performed, and then the brain sections were incubated overnight with rabbit polyclonal antibody against amino acids 2732–2750 of rat IP3R1 (1:350, #2435031, AB5882, Millipore, USA)[16] or rabbit monoclonal antibody against residues subsequent to Ser29 of human Caspase-3 (1:250, #2365527, AB4-439, Millipore, USA)[17,18] in solutions containing 5% NDS and 0.5% Triton-X 100 in PBS 0.1M at room temperature. Then, the brain sections were washed and incubated with rabbit IgG tagged to Alexa 488 (1:500, A2120-6, Life Technologies, EUA), containing phosphate buffer + 0.3% Triton X-100 + DAPI, for 2 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Functional Role of Intracellular Calcium Receptor Inositol 1,4,5-Trisphosphate Type 1 in Rat Hippocampus after Neonatal Anoxia

et al. 2017

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Anoxia is one of the most prevalent causes of neonatal morbidity and mortality, especially in preterm neonates, constituting an important public health problem due to permanent neurological sequelae observed in patients. Oxygen deprivation triggers a series of simultaneous cascades, culminating in cell death mainly located in more vulnerable metabolic brain regions, such as the hippocampus. In the process of cell death by oxygen deprivation, cytosolic calcium plays crucial roles. Intracellular inositol 1,4,5-trisphosphate receptors (IP3Rs) are important regulators of cytosolic calcium levels, although the role of these receptors in neonatal anoxia is completely unknown. This study focused on the functional role of inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) in rat hippocampus after neonatal anoxia. Quantitative real-time PCR revealed a decrease of IP3R1 gene expression 24 hours after neonatal anoxia. We detected that IP3R1 accumulates specially in CA1, and this spatial pattern did not change after neonatal anoxia. Interestingly, we observed that anoxia triggers translocation of IP3R1 to nucleus in hippocampal cells. We were able to observe that anoxia changes distribution of IP3R1 immunofluorescence signals, as revealed by cluster size analysis. We next examined the role of IP3R1 in the neuronal cell loss triggered by neonatal anoxia. Intrahippocampal injection of non-specific IP3R1 blocker 2-APB clearly reduced the number of Fluoro-Jade C and Tunel positive cells, revealing that activation of IP3R1 increases cell death after neonatal anoxia. Finally, we aimed to disclose mechanistics of IP3R1 in cell death. We were able to determine that blockade of IP3R1 did not reduced the distribution and pixel density of activated caspase 3-positive cells, indicating that the participation of IP3R1 in neuronal cell loss is not related to classical caspase-mediated apoptosis. In summary, this study may contribute to new perspectives in the investigation of neurodegenerative mechanisms triggered by oxygen deprivation.

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Dietary Vitamin D3 Restriction Exacerbates Disease Pathophysiology in the Spinal Cord of the G93A Mouse Model of Amyotrophic Lateral Sclerosis

Cited by 11 publications

References 100 publications

The neuroprotective effects of caffeine in neurodegenerative diseases

The neuroprotective effects of caffeine in neurodegenerative diseases

Is There a Role for Vitamin D in Amyotrophic Lateral Sclerosis? A Systematic Review and Meta-Analysis

Functional Role of Intracellular Calcium Receptor Inositol 1,4,5-Trisphosphate Type 1 in Rat Hippocampus after Neonatal Anoxia

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