Remodeling of the innervation of pancreatic islets accompanies insulitis preceding onset of diabetes in the NOD mouse

Persson–Sjögren, Solveig; Holmberg, Dan; Forsgren, Sture

doi:10.1016/j.jneuroim.2004.08.019

Cited by 25 publications

(14 citation statements)

References 34 publications

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“…The findings of NT effects on the nervous system include observations favoring that the p75 receptor may be related to nerve generation phases [Funakoshi et al, 1993]. Recently, we have observed that p75-expressing strands appear in association with the clusters of immune cells that become manifest during the development of insulitis in the nonobese diabetic mouse, a model of type 1 diabetes [Persson-Sjogren et al, 2005]. It was suggested that the newly formed p75-reactive strands in the immune cell clusters were related to attempts for NTs to promote nerve ingrowth and survival of the pancreatic islets [PerssonSjogren et al, 2005].…”

Section: Reaction Patterns In the Inflammatory Infiltratementioning

confidence: 93%

Expression Patterns of Neurotrophins and Neurotrophin Receptors in Articular Chondrocytes and Inflammatory Infiltrates in Knee Joint Arthritis

Grimsholm¹,

Guo

et al. 2008

Cells Tissues Organs

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Background: It is likely that neurotrophins (NTs) are of great importance for the articular cartilage and the inflammation process in arthritis. Methods: The immunohistochemical expression of the NTs nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and the associated receptors p75, TrkA and TrkB was examined in the knee joint of arthritic and healthy mice. Results: Immunoreactions for NGF and BDNF were detected in cells and nerve fiber varicosities in the inflammatory infiltrates of the synovial tissue of arthritic joints but not in synovial tissue of controls. p75-immunoreactive nerve fiber-like strands were detected in inflammatory infiltrates. Immunostaining for NGF, BDNF, p75, TrkA and TrkB was noted in articular chondrocytes. There was a statistically significant decrease in reactions for NGF (p < 0.001), TrkA (p = 0.001) and p75 (p < 0.001) in articular chondrocytes in joints exhibiting severe arthritis. Conclusion: The findings show that an NT system develops in inflammatory infiltrates of the synovial tissue. Furthermore, most interestingly, autocrine/paracrine effects appear to exist concerning NTs for the articular chondrocytes. The downregulated expression of NGF and NT receptors in articular chondrocytes in arthritis is a new aspect concerning the involvement of NTs in cartilage.

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Section: Reaction Patterns In the Inflammatory Infiltratementioning

confidence: 93%

Expression Patterns of Neurotrophins and Neurotrophin Receptors in Articular Chondrocytes and Inflammatory Infiltrates in Knee Joint Arthritis

Grimsholm¹,

Guo

et al. 2008

Cells Tissues Organs

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“…There is also growing evidence that dysfunction of the neuronal elements in the developing pancreas might be an instigating factor in the pathogenesis of pancreatic diseases. An early loss of sympathetic fibers and glial cells in the pancreas has been observed in diabetic animal models (Mei et al, 2002; Persson-Sjogren et al, 2005; Winer et al, 2003). However, whether sympathetic innervation contributes to pancreatic organogenesis remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Sympathetic Innervation during Development Is Necessary for Pancreatic Islet Architecture and Functional Maturation

et al. 2013

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Summary Sympathetic neurons depend on target-derived neurotrophic cues to control their survival and growth. However, whether sympathetic innervation contributes reciprocally to the development of target tissues is less clear. Here, we report that sympathetic innervation is necessary for the formation of the pancreatic islets of Langerhans and for their functional maturation. Genetic or pharmacological ablation of sympathetic innervation during development resulted in altered islet architecture, reduced insulin secretion and impaired glucose tolerance in mice. Similar defects were observed with pharmacological blockade of β-adrenergic signaling. Conversely, the administration of a β-adrenergic agonist restored islet morphology and glucose tolerance in de-innervated animals. Furthermore, in neuron-islet co-cultures, sympathetic neurons promoted islet cell migration in a β-adrenergic dependent manner. This study reveals that islet architecture requires extrinsic inductive cues from neighboring tissues such as sympathetic nerves, and suggests that early perturbations in sympathetic innervation might underlie metabolic disorders.

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“…One autonomic defect, which we named early sympathetic islet neuropathy (eSIN), is present in diabetic BB rats (20), NOD mice (21,22), and type 1 diabetic humans (23). This marked loss of islet sympathetic nerves is sufficient to impair the glucagon response to sympathetic activation (21,24).…”

Section: Introductionmentioning

confidence: 99%

The p75 Neurotrophin Receptor Is Required for the Major Loss of Sympathetic Nerves From Islets Under Autoimmune Attack

et al. 2014

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Our goal was to determine the role of the p75 neurotrophin receptor (p75NTR) in the loss of islet sympathetic nerves that occurs during the autoimmune attack of the islet. The islets of transgenic (Tg) mice in which β-cells express a viral glycoprotein (GP) under the control of the insulin promotor (Ins2) were stained for neuropeptide Y before, during, and after virally induced autoimmune attack of the islet. Ins2-GPTg mice injected with lymphocytic choriomeningitis virus (LCMV) lost islet sympathetic nerves before diabetes development but coincident with the lymphocytic infiltration of the islet. The nerve loss wasmarked and islet-selective. Similar nerve loss, chemically induced, was sufficient to impair sympathetically mediated glucagon secretion. In contrast, LCMV-injected Ins2-GPTg mice lacking the p75NTR retained most of their islet sympathetic nerves, despite both lymphocytic infiltration and development of diabetes indistinguishable from that of p75NTR wild-type mice. We conclude that an nducible autoimmune attack of the islet causes a marked and islet-selective loss of sympathetic nerves that precedes islet collapse and hyperglycemia. The p75NTR mediates this nerve loss but plays no role in mediating the loss of islet β-cells or the subsequent diabetes. p75NTR-mediated nerve loss may contribute to the impaired glucose counterregulation seen in type 1 diabetes.

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Remodeling of the innervation of pancreatic islets accompanies insulitis preceding onset of diabetes in the NOD mouse

Cited by 25 publications

References 34 publications

Expression Patterns of Neurotrophins and Neurotrophin Receptors in Articular Chondrocytes and Inflammatory Infiltrates in Knee Joint Arthritis

Expression Patterns of Neurotrophins and Neurotrophin Receptors in Articular Chondrocytes and Inflammatory Infiltrates in Knee Joint Arthritis

Sympathetic Innervation during Development Is Necessary for Pancreatic Islet Architecture and Functional Maturation

The p75 Neurotrophin Receptor Is Required for the Major Loss of Sympathetic Nerves From Islets Under Autoimmune Attack

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