Glucose neurotoxicity

Tomlinson, David R.; Gardiner, Natalie J.

doi:10.1038/nrn2294

Cited by 475 publications

(413 citation statements)

References 128 publications

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“…Deficits in large fibre conduction velocity are generally considered to be among the earliest functional markers of glucose neurotoxicity, as they typically present before decreases in axonal diameter or structural disruption of the myelin in rodents 152 . In the absence of structural pathology, impaired nodal biophysical properties, such as ion flux and current densities, that might involve Schwann cell dysfunction have been implicated 152,153 .…”

Section: Impact Of Schwannopathy On Neuronsmentioning

confidence: 99%

“…In the absence of structural pathology, impaired nodal biophysical properties, such as ion flux and current densities, that might involve Schwann cell dysfunction have been implicated 152,153 . A study of rats with STZ-induced diabetes has shown that reduced motor conduction velocity is associated with upregulation of the Rho-Rho-kinase signalling pathway and consequent misexpression and aberrant distribution of the myelin sheath adhesion molecules p120 catenin and epithelial cadherin, which are crucial for normal myelin formation to allow rapid propagation of action potentials 154 .…”

Section: Impact Of Schwannopathy On Neuronsmentioning

confidence: 99%

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Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

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The incidence of diabetes mellitus has increased dramatically over the past two to three decades. According to the International Diabetes Federation Diabetes Atlas, 415 million people worldwide had diabetes in 2015, and this number is expected to grow by 5% annually, predominantly as a result of increasing prevalence of type 2 diabetes. Furthermore, an estimated 100 million Europeans and 80 million Americans have impaired glucose tolerance or prediabetes. Few people die from acute diabetes in countries with comprehensive health care systems, but the disease is inflicting a huge medical, social and economic burden on society owing to the need for lifelong treatment of its systemic consequences and the insidious development of multi-organ damage.Peripheral neuropathy (BOXES 1,2) is a common but often neglected complication of long-term diabetes, and the lack of treatment options reflects an incomplete understanding of the pathogenic mechanisms. Hyperglycaemia is generally accepted as the primary pathogenic insult in type 1 and type 2 diabetic neuropathy, although roles are emerging for other factors, such as impaired insulin signalling, hypertension and dyslipidaemia (particularly for type 2 diabetes), which might precede overt hyperglycaemia 1 . Many preclinical studies, and occasional clinical studies, have indicated that diabetic neuropathy -like diabetic nephropathy and retinopathy -results from microvascular disease, with a focus on axonal degeneration as a consequence of ischaemia and/or hypoxia. This mechanism, however, is likely to be only one aspect of a more complex pathogenesis.The earliest descriptions of pathology in diabetic neuropathy indicated that Schwannopathy accompanied axonal degeneration. The majority of clinical and basic research in diabetic neuropathy since then has focused on the effects on neurons. However, accumulating data from research into the development and regeneration of the PNS has identified Schwann cells as equally indispensable components that maintain neuronal structure and function, nourish axons, and promote survival and growth upon injury. The early reports from 1979 that demonstrated morphological changes in Schwann cells in human diabetic neuropathy 2 are now supported by an increased awareness of molecular alterations in Schwann cells during diabetes 3 . Schwann cells express a wide range of receptors and, when they sense insults or danger signals, they upregulate synthesis and secretion of factors that stimulate neuroprotection, regrowth and remyelination, or factors that aggravate disease phenotypes 4 . The most recent studies have demonstrated that Schwann cells regulate many aspects of axonal function, so that disruption of their metabolism by diabetes results in the accumulation of neurotoxic intermediates and compromises production of neuronal support factors, contributing to axonal degeneration, endothelial dysfunction and diabetic neuropathy. Abstract | The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annu...

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Section: Impact Of Schwannopathy On Neuronsmentioning

confidence: 99%

Section: Impact Of Schwannopathy On Neuronsmentioning

confidence: 99%

Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

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“…8 It has also been suggested that increased intracellular osmotic pressure via polyol (sorbitol) pathway would attribute to the changes in Tau and Ins levels observed in the diabetic brain. 24 The reasons underlying the differential changes of Tau in the striatum and hippocampus are unclear, but could be related to the fact that STZ-induced T1DM results in more severely perturbed glucose metabolism in the hippocampus than in the striatum. 25 Visual Cortex A number of clinical studies have investigated T1DM-related metabolic changes in the frontal 3,6 and occipital 5,26 cortex.…”

Section: Region-specific Metabolic Alterations At 4 Weeksmentioning

confidence: 99%

Region-Specific Cerebral Metabolic Alterations in Streptozotocin-Induced Type 1 Diabetic Rats: An in vivo Proton Magnetic Resonance Spectroscopy Study

Zhang

Huang

Gao

et al. 2015

J Cereb Blood Flow Metab

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Clinical and experimental in vivo 1 H-magnetic resonance spectroscopy ( 1 H-MRS) studies have demonstrated that type 1 diabetes mellitus (T1DM) is associated with cerebral metabolic abnormalities. However, less is known whether T1DM induces different metabolic disturbances in different brain regions. In this study, in vivo 1 H-MRS was used to measure metabolic alterations in the visual cortex, striatum, and hippocampus of streptozotocin (STZ)-induced uncontrolled T1DM rats at 4 days and 4 weeks after induction. It was observed that altered neuronal metabolism occurred in STZ-treated rats as early as 4 days after induction. At 4 weeks, T1DM-related metabolic disturbances were clearly region specific. The diabetic visual cortex had more or less normalappearing metabolic profile; while the striatum and hippocampus showed similar abnormalities in neuronal metabolism involving N-acetyl aspartate and glutamate; but only the hippocampus exhibited significant changes in glial markers such as taurine and myo-inositol. It is concluded that cerebral metabolic perturbations in STZ-induced T1DM rats are region specific at 4 weeks after induction, perhaps as a manifestation of varied vulnerability among the brain regions to sustained hyperglycemia.

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“…In aging, hyperglycemia is also associated with PD through damage to the central nervous system, a consequence of long-term exposure to glucose (Tomlinson and Gardiner 2008;Hu et al 2007). Epidemiologic studies suggest that previous type 2 diabetes is also a risk factor for developing PD (Mercer et al 2005).…”

Section: Brain Neurons and Parkinson's Diseasementioning

confidence: 99%

Aging of perennial cells and organ parts according to the programmed aging paradigm

Libertini

Ferrara

2016

AGE

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If aging is a physiological phenomenon-as maintained by the programmed aging paradigm-it must be caused by specific genetically determined and regulated mechanisms, which must be confirmed by evidence. Within the programmed aging paradigm, a complete proposal starts from the observation that cells, tissues, and organs show continuous turnover: As telomere shortening determines both limits to cell replication and a progressive impairment of cellular functions, a progressive decline in age-related fitness decline (i.e., aging) is a clear consequence. Against this hypothesis, a critic might argue that there are cells (most types of neurons) and organ parts (crystalline core and tooth enamel) that have no turnover and are subject to wear or manifest alterations similar to those of cells with turnover. In this review, it is shown how cell types without turnover appear to be strictly dependent on cells subjected to turnover. The loss or weakening of the functions fulfilled by these cells with turnover, due to telomere shortening and turnover slowing, compromises the vitality of the served cells without turnover. This determines well-known clinical manifestations, which in their early forms are described as distinct diseases (e.g., Alzheimer's disease, Parkinson's disease, age-related macular degeneration, etc.). Moreover, for the two organ parts (crystalline core and tooth enamel) without viable cells or any cell turnover, it is discussed how this is entirely compatible with the programmed aging paradigm.

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Glucose neurotoxicity

Cited by 475 publications

References 128 publications

Schwann cell interactions with axons and microvessels in diabetic neuropathy

Schwann cell interactions with axons and microvessels in diabetic neuropathy

Region-Specific Cerebral Metabolic Alterations in Streptozotocin-Induced Type 1 Diabetic Rats: An in vivo Proton Magnetic Resonance Spectroscopy Study

Aging of perennial cells and organ parts according to the programmed aging paradigm

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