Islet injury induces neurotrophin expression in pancreatic cells and reactive gliosis of peri-islet Schwann cells

Teitelman, Gladys; Guz, Yelena; Ivković, Sanja; Ehrlich, Michelle E.

doi:10.1002/(sici)1097-4695(199803)34:4<304::aid-neu2>3.0.co;2-a

Cited by 57 publications

(45 citation statements)

References 57 publications

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“…3b shows that the toxicity of STZ leads to beta cell destruction. This chemically induced injury has been shown to increase the neurotrophin content in the islet [29,30], in which we observe an outgrowth of TH + nerves around the blood vessels, particularly in the islet core. Compared with the normal beta cells in the non-treated control (Fig.…”

Section: Resultsmentioning

confidence: 50%

3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury

Chiu

Hua

et al. 2012

Diabetologia

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Aims/hypothesis Sympathetic nerves influence islet hormone levels in the circulation. Insights into islet sympathetic innervation and its remodelling in diabetes may impact future therapeutics. However, standard immunohistochemistry and microtome-based microscopy cannot provide an integral view of the islet neurovascular complex. We prepared transparent islet specimens to investigate the spatial relationship between sympathetic nerves, blood vessels and islet cells in normal, streptozotocin-injected and non-obese diabetic mouse models. Methods Cardiac perfusion of fluorescent lectin was used to label pancreatic blood vessels. Tyrosine hydroxylase and nuclear staining were used to reveal islet sympathetic innervation and microstructure. Optical clearing (i.e. use of immersion solution to reduce scattering) was applied to enable 3-dimensional confocal microscopy of islets to visualise the sympathetic neurovascular complex in space. Results Unlike previously reported morphology, we observed perfusive intra-islet, perivascular sympathetic innervation, in addition to peri-islet contacts of sympathetic nerves with alpha cells and sympathetic fibres encircling the adjacent arterioles. The intra-islet axons became markedly prominent in streptozotocin-injected mice (2 weeks after injection). In non-obese diabetic mice, lymphocytic infiltration remodelled the peri-islet sympathetic axons in early insulitis. Conclusions/interpretation We have established an imaging approach to reveal the spatial features of mouse islet sympathetic innervation. The neurovascular complex and sympathetic nerve-alpha cell contact suggest that sympathetic nerves modulate islet hormone secretion through blood vessels, in addition to acting directly on alpha cells. In islet injuries, sympathetic nerves undergo different remodelling in response to different pathophysiological cues.

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Section: Resultsmentioning

confidence: 50%

3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury

Chiu

Hua

et al. 2012

Diabetologia

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“…In the peripheral nervous system, Sox10 and Sox8 are expressed in glial cells and Sox10 has been shown to be required for the development of these cells (Britsch et al, 2001;Sock et al, 2001). Because pancreatic islets are enveloped in a sheath of glial cells (Teitelman et al, 1998), it is possible that the Sox10-positive cells in the pancreas are indeed glial cells. Our finding that no ␤-galactosidase-positive cells could be detected in pancreas of Sox10 mutant embryos (data not shown) further suggests that these cells require Sox10 for their development.…”

Section: Resultsmentioning

confidence: 99%

Expression of Sox transcription factors in the developing mouse pancreas

Lioubinski¹,

Müller²,

Wegner

et al. 2003

Developmental Dynamics

113

128

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Previous work has identified members of the homeodomain and basic helix-loop-helix families of transcription factors as critical determinants of mammalian pancreatic development. Here, we describe the identification of HMG-box transcription factors of the Sox gene family in the mouse pancreas. We detected transcripts for Sox11, Sox4, Sox13, Sox5, Sox9, Sox8, Sox10, Sox7, Sox17, Sox18, Sox15, and Sox30 in embryonic pancreas and found Sox4, Sox9, and Sox13 in adult pancreatic islets. Expression of seven of these Sox factors was studied in more detail by in situ hybridization from the stage of early pancreatic outgrowth to birth. Expression of Sox11 was found in the mesenchyme surrounding the pancreatic buds, whereas Sox4 and Sox9 were confined to the pancreatic epithelium and later to islets. Sox13 and L-Sox5 showed expression in most of the pancreatic epithelial cells between embryonic days 12.5 and 14.5. Sox8 and Sox10 were detected in a thin layer of cells surrounding the islets. The expression patterns of Sox genes in the embryonic pancreas suggest that they could have important and possibly redundant functions in pancreas development. Developmental Dynamics 227:402-408, 2003.

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“…They found that the peri-islet lymphocytic accumulation in insulitis creates disturbances and breaches of the glial sheath prior to the autoimmune attack on the beta cells [14][15][16]. Interestingly, in contrast to the destruction of Schwann cells, reactive gliosis was also reported in streptozotocin (STZ)-injected mice [17]. The variation in islet glial-cell content in animal models of diabetes highlights Schwann cells as a dynamic cellular factor involved in islet injury and inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…This allowed the identification of the spatial features of the GFAP + Schwann cells and NG2 + pericytes (note: although named as a neuron-'glial' antigen, the NG2 cell-surface chondroitin sulfate proteoglycan is highly expressed in the pancreatic/islet pericytes and has been used as a histological marker [5,33]) and their association with the islet lesion and vasculature [13,17,[34][35][36]. Qualitative and quantitative analyses of the islet injury-induced gliosis and pericyte remodelling around the feeding arteriole, and their pathophysiological implications, are presented and discussed in this report.…”

Section: Introductionmentioning

confidence: 99%

Plasticity of Schwann cells and pericytes in response to islet injury in mice

et al. 2013

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Aims/hypothesis Islet Schwann (glial) cells and pericytes are the microorgan's accessory cells positioned at the external and internal boundaries facing the exocrine pancreas and endothelium, respectively, adjacent to the endocrine cells. Plasticity of glial cells and pericytes is shown in the glial scar formation after injury to the central nervous system. It remains unclear whether similar reactive cellular responses occur in insulitis. We applied three-dimensional (3D) histology to perform qualitative and quantitative analyses of the islet Schwann cell network and pericytes in normal, streptozotocin-injected (positive control of gliosis) and NOD mouse models. Methods Vessel painting paired with immunostaining of mouse pancreatic tissue was used to reveal the islet Schwann cells and pericytes and their association with vasculature. Transparent islet specimens were prepared by optical clearing to facilitate 3D confocal microscopy for panoramic visualisation of the tissue networks.Results In-depth microscopy showed that the islet Schwann cell network extends from the peri-islet domain into the core. One week after streptozotocin injection, we observed intraislet perivascular gliosis and an increase in pericyte density. In early/moderate insulitis in the NOD mice, perilesional gliosis occurred at the front of the lymphocytic infiltration with atypical islet Schwann cell morphologies, including excessive branching and perivascular gliosis. Meanwhile, pericytes aggregated on the walls of the feeding arteriole at the peri-and intralesional domains with a marked increase in surface marker density. Conclusions/interpretationThe reactive cellular responses demonstrate plasticity and suggest a stop-gap mechanism consisting of the Schwann cells and pericytes in association with the islet lesion and vasculature when injury occurs.

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Islet injury induces neurotrophin expression in pancreatic cells and reactive gliosis of peri-islet Schwann cells

Cited by 57 publications

References 57 publications

3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury

3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury

Expression of Sox transcription factors in the developing mouse pancreas

Plasticity of Schwann cells and pericytes in response to islet injury in mice

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