Lucha
Member
- Joined
- Nov 27, 2015
- Messages
- 12
Good day to everybody who reads.
Several days ago i made quite a stupid post about taurine and meldonum for autism and adhd. Some answers put me on a right way. Thank you very much.
So, i have a three years daughter with SMA deletion. It is not full disease but a part of it (more information about symptoms in that post). At the same time she has ADHD and possible beginning of autism. I read about adhd and autism as a complex of metabolic disorders and now try to name them can help to find an optimal decision. I think it may be helpful for us and for somebody else.
Looks like too many names for just a few conditions. For now it seems very similar to diabetes (unopposed glucagon, iron overload), in publications i saw cases of comorbidity SMA and diabetes 1.
Many information about role of serotonin on the forum but still cannot understand is it main player or just effect (one of symptoms) of condition. Would be appreciate for any thoughts.
To begin with...
Evidence of neurodegeneration in autism spectrum disorder
"Evidence of neurodegeneration in the brain in ASD includes: (1) neuronal cell loss, (2) activated microglia and astrocytes, (3) proinflammatory cytokines, (4) oxidative stress, and (5) elevated 8-oxo-guanosine levels. The evidence from this review suggests that neurodegeneration underlies the loss of neurological function in children with ASD who have experienced regression and loss of previously acquired skills and abilities, and that research into treatments to address the issue of neurodegeneration in ASD are warranted."
Then, is SMA (like others neurodegeneration) is an insulin resistance...
Glucose Metabolism and Pancreatic Defects in Spinal Muscular Atrophy
"Here, we demonstrate in an SMA mouse model a dramatic cell fate imbalance within pancreatic islets, with a predominance of glucagon-producing α cells at the expense of insulin-producing β cells. These SMA mice display fasting hyperglycemia, hyperglucagonemia, and glucose resistance. We demonstrate similar abnormalities in pancreatic islets from deceased children with the severe infantile form of SMA in association with supportive evidence of glucose intolerance in at least a subset of such children."
Increased IGF-1 in muscle modulates the phenotype of severe SMA mice. - PubMed - NCBI
"We hypothesized that increased expression of IGF-1 specifically in skeletal muscle would attenuate disease features of SMAΔ7 mice. SMAΔ7 mice overexpressing a local isoform of IGF-1 (mIGF-1) in muscle showed enlarged myofibers and a 40% increase in median survival compared with mIGF-1-negative SMA littermates (median survival = 14 versus 10 days, respectively, log-rank P = 0.025). Surprisingly, this was not associated with a significant improvement in motor behavior."
IGF-1R Reduction Triggers Neuroprotective Signaling Pathways in Spinal Muscular Atrophy Mice. - PubMed - NCBI
"Recent evidence of IGF-1 axis alteration in spinal muscular atrophy (SMA), a very severe neurodegenerative disease affecting specifically the motor neurons, have triggered a renewed interest in insulin-like growth factor-1 (IGF-1) pathway activation as a potential therapeutic approach for motor neuron diseases. The present study challenges this point of view and brings the alternative hypothesis that reducing rather than enhancing the IGF-1 signaling pathway exerts a neuroprotective effect in SMA. Furthermore, the present data substantiate a newly emerging concept that the modulation of IGF-1 receptor expression is a key event selectively determining the activation level of intracellular pathways that lie downstream of the receptor. This aspect should be considered when designing IGF-1-based treatments for neurodegenerative diseases."
Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy. - PubMed - NCBI
"Revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) correlated positively with HDL-C, but negatively with HOMA-IR. Through stepwise multiple regression analysis, we identified HOMA-IR as a significant metabolic determinant of ALSFRS-R. In biochemical analysis, we found that decreased expressions of insulin receptors, insulin receptor substrate-1 and insulin receptor-β, in autopsied muscles and fibroblasts of SBMA patients. This study demonstrates that SBMA patients have insulin resistance, which is associated with the disease severity. The expressions of insulin receptors are attenuated in the skeletal muscle of SBMA, providing a possible pathomechanism of metabolic alterations. These findings suggested that insulin resistance is a metabolic index reflecting disease severity and pathogenesis as well as a potential therapeutic target for SBMA."
Elevated plasma glucagon in amyotrophic lateral sclerosis. - PubMed - NCBI
"...glucagon levels were elevated in all ALS patients compared with controls: at fasting (237 +/- 111 versus 108 +/- 46 pg/ml, p less than 0.01) and 1/2 hour (389 +/- 94 versus 133 +/- 68 pg/ml, p less than 0.001), and 2 hours postprandial (379 +/- 75 versus 108 +/- 53 pg/ml, p less than 0.001)."
...and iron overload...
Survival Motor Neuron (SMN) protein is required for normal mouse liver development
"The pronounced dark-red phenotype in SMA liver is consistent with the observed increase in RBC as a result of on-going erythropoiesis and iron overload, which is necessary for erythroblast maturation51. Therefore, iron accumulation and accompanying decrease in Ireb-2 mRNA expression in SMA liver are a likely outcome of persistent active erythropoiesis at later stages of development. Ireb-2, which is a key regulator of vertebrate cellular iron homeostasis37, is significantly reduced in embryonic stem cells with low SMN protein38. Further, motor neurons from Ireb-2−/− mice display increased ferritin and impaired mitochondrial function resulting in motor neuron degeneration52. We show increased hepatic iron and significant a reduction in Ireb-2 mRNA in SMA liver, which taken together with mitochondrial dysfunction in SMA53,54,55, suggests that iron dysregulation may be important in motor neuron degeneration, and a candidate for further study in SMA."
Brain iron and ferritin in Parkinson's and Alzheimer's diseases.
"The results indicate a significant selective increase of Fe3+ and ferritin in substantia nigra zona compacta but not in zona reticulata of Parkinsonian brains, confirming the biochemical estimation of iron. No such changes were observed in the same regions of DAT brains. The increase of iron is evident in astrocytes, macrophages, reactive microglia and non-pigmented neurons, and in damaged areas devoid of pigmented neurons. In substantia nigra of PD and PD/DAT, strong ferritin reactivity was also associated with proliferated microglia".
Several days ago i made quite a stupid post about taurine and meldonum for autism and adhd. Some answers put me on a right way. Thank you very much.
So, i have a three years daughter with SMA deletion. It is not full disease but a part of it (more information about symptoms in that post). At the same time she has ADHD and possible beginning of autism. I read about adhd and autism as a complex of metabolic disorders and now try to name them can help to find an optimal decision. I think it may be helpful for us and for somebody else.
Looks like too many names for just a few conditions. For now it seems very similar to diabetes (unopposed glucagon, iron overload), in publications i saw cases of comorbidity SMA and diabetes 1.
Many information about role of serotonin on the forum but still cannot understand is it main player or just effect (one of symptoms) of condition. Would be appreciate for any thoughts.
To begin with...
Evidence of neurodegeneration in autism spectrum disorder
"Evidence of neurodegeneration in the brain in ASD includes: (1) neuronal cell loss, (2) activated microglia and astrocytes, (3) proinflammatory cytokines, (4) oxidative stress, and (5) elevated 8-oxo-guanosine levels. The evidence from this review suggests that neurodegeneration underlies the loss of neurological function in children with ASD who have experienced regression and loss of previously acquired skills and abilities, and that research into treatments to address the issue of neurodegeneration in ASD are warranted."
Then, is SMA (like others neurodegeneration) is an insulin resistance...
Glucose Metabolism and Pancreatic Defects in Spinal Muscular Atrophy
"Here, we demonstrate in an SMA mouse model a dramatic cell fate imbalance within pancreatic islets, with a predominance of glucagon-producing α cells at the expense of insulin-producing β cells. These SMA mice display fasting hyperglycemia, hyperglucagonemia, and glucose resistance. We demonstrate similar abnormalities in pancreatic islets from deceased children with the severe infantile form of SMA in association with supportive evidence of glucose intolerance in at least a subset of such children."
Increased IGF-1 in muscle modulates the phenotype of severe SMA mice. - PubMed - NCBI
"We hypothesized that increased expression of IGF-1 specifically in skeletal muscle would attenuate disease features of SMAΔ7 mice. SMAΔ7 mice overexpressing a local isoform of IGF-1 (mIGF-1) in muscle showed enlarged myofibers and a 40% increase in median survival compared with mIGF-1-negative SMA littermates (median survival = 14 versus 10 days, respectively, log-rank P = 0.025). Surprisingly, this was not associated with a significant improvement in motor behavior."
IGF-1R Reduction Triggers Neuroprotective Signaling Pathways in Spinal Muscular Atrophy Mice. - PubMed - NCBI
"Recent evidence of IGF-1 axis alteration in spinal muscular atrophy (SMA), a very severe neurodegenerative disease affecting specifically the motor neurons, have triggered a renewed interest in insulin-like growth factor-1 (IGF-1) pathway activation as a potential therapeutic approach for motor neuron diseases. The present study challenges this point of view and brings the alternative hypothesis that reducing rather than enhancing the IGF-1 signaling pathway exerts a neuroprotective effect in SMA. Furthermore, the present data substantiate a newly emerging concept that the modulation of IGF-1 receptor expression is a key event selectively determining the activation level of intracellular pathways that lie downstream of the receptor. This aspect should be considered when designing IGF-1-based treatments for neurodegenerative diseases."
Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy. - PubMed - NCBI
"Revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) correlated positively with HDL-C, but negatively with HOMA-IR. Through stepwise multiple regression analysis, we identified HOMA-IR as a significant metabolic determinant of ALSFRS-R. In biochemical analysis, we found that decreased expressions of insulin receptors, insulin receptor substrate-1 and insulin receptor-β, in autopsied muscles and fibroblasts of SBMA patients. This study demonstrates that SBMA patients have insulin resistance, which is associated with the disease severity. The expressions of insulin receptors are attenuated in the skeletal muscle of SBMA, providing a possible pathomechanism of metabolic alterations. These findings suggested that insulin resistance is a metabolic index reflecting disease severity and pathogenesis as well as a potential therapeutic target for SBMA."
Elevated plasma glucagon in amyotrophic lateral sclerosis. - PubMed - NCBI
"...glucagon levels were elevated in all ALS patients compared with controls: at fasting (237 +/- 111 versus 108 +/- 46 pg/ml, p less than 0.01) and 1/2 hour (389 +/- 94 versus 133 +/- 68 pg/ml, p less than 0.001), and 2 hours postprandial (379 +/- 75 versus 108 +/- 53 pg/ml, p less than 0.001)."
...and iron overload...
Survival Motor Neuron (SMN) protein is required for normal mouse liver development
"The pronounced dark-red phenotype in SMA liver is consistent with the observed increase in RBC as a result of on-going erythropoiesis and iron overload, which is necessary for erythroblast maturation51. Therefore, iron accumulation and accompanying decrease in Ireb-2 mRNA expression in SMA liver are a likely outcome of persistent active erythropoiesis at later stages of development. Ireb-2, which is a key regulator of vertebrate cellular iron homeostasis37, is significantly reduced in embryonic stem cells with low SMN protein38. Further, motor neurons from Ireb-2−/− mice display increased ferritin and impaired mitochondrial function resulting in motor neuron degeneration52. We show increased hepatic iron and significant a reduction in Ireb-2 mRNA in SMA liver, which taken together with mitochondrial dysfunction in SMA53,54,55, suggests that iron dysregulation may be important in motor neuron degeneration, and a candidate for further study in SMA."
Brain iron and ferritin in Parkinson's and Alzheimer's diseases.
"The results indicate a significant selective increase of Fe3+ and ferritin in substantia nigra zona compacta but not in zona reticulata of Parkinsonian brains, confirming the biochemical estimation of iron. No such changes were observed in the same regions of DAT brains. The increase of iron is evident in astrocytes, macrophages, reactive microglia and non-pigmented neurons, and in damaged areas devoid of pigmented neurons. In substantia nigra of PD and PD/DAT, strong ferritin reactivity was also associated with proliferated microglia".
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