NMDA and AMPA glutamate receptor subtypes in the thoracic spinal cord in lean and obese–diabetic ob/ob mice

Li, Nicholas; Young, Margaret M.; Bailey, Clifford J.; Smith, Margaret E.

doi:10.1016/s0006-8993(99)02070-3

Cited by 36 publications

(19 citation statements)

References 24 publications

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“…Therefore, it could be hypothesized that glutamate receptor properties can be differentially modulated, depending on the duration of diabetes [3]. Nevertheless, our data are concordant with a recent study reporting up-regulation of both NMDA and AMPA receptors in thoracic spinal cord sections from obese-diabetic ob/ob mice, another model in which animals develop diabetes spontaneously and which closely resembles the Type II (insulin-independent) condition [45].…”

Section: Discussionsupporting

confidence: 91%

“…In particular, our data indicating that up-regulation of glutamate receptors is related to LTP defects in the early stages of diabetes, are in line with the recent observation that early changes in glutamate receptors could be causally involved in the peripheral neuropathies which can accompany diabetes mellitus [45]. Identifying the mechanisms by which these biochemical and electrophysiological changes are exerted could provide important clues about the cellular events responsible for diabetes-induced neuropathies.…”

Section: Discussionsupporting

confidence: 90%

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Up-regulation of glutamate receptors is associated with LTP defects in the early stages of diabetes mellitus

et al. 2002

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Aims/hypothesis. Recent studies involving electrophysiology and immunolabelling indicate that shortterm insulin treatment of hippocampal neurons in culture induces changes in glutamate receptor function, suggesting that this receptor system can be altered on a relatively rapid time scale during diabetic conditions. To investigate this hypothesis, we examined whether brain glutamate receptors and long-term potentiation are altered in the early stages of diabetes mellitus in non-obese diabetic mice, a genetic model of Type I (insulin-dependent) diabetes mellitus. Methods. In vitro receptor autoradiography and immunoblotting were used to study the impact of diabetes on brain glutamate receptors. From an electrophysiological point of view, field potential recordings were also examined in area CA1 of hippocampal slices to determine the influence of diabetes on long-term potentiation.Results. Quantitative autoradiographic analysis revealed enhanced 3 H-glutamate binding to several brain regions of diabetes mice, with maximal increases in the cerebral cortex and hippocampus. Saturation kinetics within the cerebral cortex disclosed that this change of 3 H-glutamate was possibly due to an increase in the maximal number of N-methyl-D-aspartate binding sites, an interpretation that was corroborated by Western blot analysis of N-methyl-D-aspartate 2A subunits. Impairment in the expression of hippocampal long-term potentiation was also observed in diabetic mice, while the failure to elicit synaptic potentiation was prevented by insulin treatment. Conclusion/interpretation. Because glutamate receptors are thought to be involved in several degenerative processes, our results suggest that up-regulation of these receptors in the early stages of diabetes could represent an important mechanism underlying neurological complications within the brain of diabetic patients. [Diabetologia (2002) 45:642-650] Keywords NMDA receptor, AMPA receptor, hippocampus, NOD mice. According to recent projections, over 200 million people worldwide will be diagnosed with diabetes by the year 2010 [1]. Diabetes mellitus is an endocrine disorder of carbohydrate metabolism resulting primarily from inadequate insulin release (Type I insulin-dependent diabetes mellitus) or insulin insensitivity coupled with inadequate compensatory insulin release (Type II non-insulin-dependent diabetes mellitus). Forms of diabetes are associated with the development of complications in the peripheral as well as the central nervous system (CNS). For instance, learning and memory deficits are linked with Type I and Type II diabetes mellitus [2, 3, 4, 5, 6], and brain morphological abnor-

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Up-regulation of glutamate receptors is associated with LTP defects in the early stages of diabetes mellitus

et al. 2002

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“…Ng et al (2004) have shown an increase in GluR2/3 subunit expression in ganglion, amacrine and bipolar cells as well as in the inner and outer plexiform layers in one and four weeks STZ-induced diabetic rats. In addition, the ob/ob mouse, a model of type 2 diabetes, was found to have increased binding sites for AMPA and NMDA receptors in the gray matter of the spinal cord (Li et al, 1999). In the brain of STZ-diabetic rats the binding properties of AMPA receptors and the expression of NMDA receptor subunits were also altered (Di Luca et al, 1999;Gagne et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Diabetes changes ionotropic glutamate receptor subunit expression level in the human retina

et al. 2008

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Early diabetic retinopathy is characterized by changes in subtle visual functions such as contrast sensitivity and dark adaptation. The outcome of several studies suggests that glutamate is involved in retinal neurodegeneration during diabetes. We hypothesized that the protein levels of ionotropic glutamate receptor subunits are altered in the retina during diabetes. Therefore, we investigated whether human diabetic patients have altered immunoreactivity of ionotropic glutamate receptor subunits in the retina. In total, 12 donor eyes from subjects with diabetes mellitus were examined and compared to 6 eyes from non-diabetic subjects without known ocular disease, serving as controls. Immunohistochemical analysis was performed using specific antibodies directed against the ionotropic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor subunits GluR1, GluR2, GluR4, and against the N-methyl-D-aspartate glutamate receptor subunit NR1. In the inner plexiform and outer plexiform layers the immunoreactivity of GluR2 and NR1 subunits was significantly increased in subjects with diabetes when compared to the levels found in controls. No significant changes in GluR1 and GluR4 subunit expression were observed.These results suggest that early visual dysfunction in diabetic patients may be due, at least partially, to changes in glutamate receptor subunit expression or distribution. IntroductionDiabetic retinopathy (DR) is a leading cause of blindness in working-age adults in developed countries. The vascular changes that occur in DR are well documented, and include loss of pericytes and endothelial cells, the formation of microaneurysms, basement membrane thickening and blood-retinal barrier breakdown (Cai and Boulton, 2002). In addition to the vascular

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“…Excessive glutamate over-activates the cognate receptors, specifically NMDA receptors, which gives the influx of high level of Ca 2+ in the post-synaptic cell. In the diabetic brain the glutamate level and the number of GluRs are significantly increased, which is the main cause of neurodegenerative changes in DM (N. Li et al, 1999;Tomiyama et al, 2005;Joseph et al, 2008;Anu et al, 2010) (Fig. 3).…”

Section: Glutamate Signalingmentioning

confidence: 99%

“…In the deep dorsal horn of STZ rats the level of NMDA receptors with high affinity for glutamate, namely NR1/NR2A or NR1/NR2B receptors, was the highest. Also increased was the number of NMDA and AMPA receptors in the gray matter of the spinal cord of the ob/ob mice responsible for pain, sensory perception and muscle control (N. Li et al, 1999). Thus, the elevated level of specific GluRs/GluR subunits in the spinal cord is a precondition for the pathogenesis of sensory impairment leading to diabetic neuropathy in DM.…”

Section: Fig 3 Signaling Pathways Responsible For Glutamate Toxicitymentioning

confidence: 99%

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

Шпаков¹,

Chistyakova²,

Derkach³

et al. 2011

Neurodegenerative Diseases - Processes, Prevention, Protection and Monitoring

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NMDA and AMPA glutamate receptor subtypes in the thoracic spinal cord in lean and obese–diabetic ob/ob mice

Cited by 36 publications

References 24 publications

Up-regulation of glutamate receptors is associated with LTP defects in the early stages of diabetes mellitus

Up-regulation of glutamate receptors is associated with LTP defects in the early stages of diabetes mellitus

Diabetes changes ionotropic glutamate receptor subunit expression level in the human retina

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

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