Characterization of the Proapoptotic Intracellular Mechanisms Induced by a Toxic Conformer of the Recombinant Human Prion Protein Fragment 90–231

Adeghate, Ernest; Rashed, Hameed; Rajbandari, Satyan; Singh, Jaipaul

doi:10.1196/annals.1372.030

Cited by 18 publications

(7 citation statements)

References 43 publications

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“…In this study, the significant reduction of CGRP may be associated with impairments of these trophic functions. This result was supported by previous study that the number of CGRP-positive neurons was significantly decreased in type 1 and 2 diabetic rats compared to their controls [ 46 ].…”

Section: Discussionsupporting

confidence: 87%

SP, CGRP changes in pyridoxine induced neuropathic dogs with nerve growth factor gene therapy

et al. 2016

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BackgroundNerve growth factor (NGF) is known not only as a major factor for neuronal plasticity but also as a pain stimulator. Although there have been several trials with NGF for its application in the regeneration or protection of the nervous system, the pain induced by NGF remains a challenge to be overcome. In this study, the pain induced by NGF gene therapy was evaluated.ResultsVehicle or recombinant dog NGF plasmid was administered into the intrathecal space of dogs. Twenty-four hours after the vehicle or NGF plasmid inoculation, dogs were subcutaneously treated with 150 mg/kg pyridoxine every day for 7 days. For pain assessment, physical examination and electrophysiological recording were performed. Only in the vehicle-treated group, weight loss occurred, while NGF plasmid inoculation significantly improved this physical abnormalities. In the vehicle-treated group, electrophysiological recordings showed that H-reflex disappeared at 24 h after the last pyridoxine treatment. However, in the NGF plasmid inoculated group, the H-reflex were normal. In the results of immunohistochemistry, the NGF plasmid administration efficiently expressed in the dorsal root ganglia and significantly increased the pyridoxine-induced reduction of calcitonin gene-related peptide (CGRP) immunoreactive neurons, but not in substance P immunoreactive neurons, in the dorsal root ganglia.ConclusionsGiven these results, we reason that NGF gene therapy in pyridoxine induced neuropathic dogs does not induce neuropathic pain with this dosage, even with increasing the expression of CGRP.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-015-0236-5) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 87%

SP, CGRP changes in pyridoxine induced neuropathic dogs with nerve growth factor gene therapy

et al. 2016

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“…The relative exclusivity among MrgD-GFP- and CGRP-expressing DRG neurons (55) allow for the evaluation of C-fiber subtypes at the level of the free nerve ending. The approach used here involving GFP transgene expression in conjunction with PGP9.5 immunostaining, compared to alternative techniques using immunostaining for multiple neuropeptide markers, avoids confounds associated with diabetes-induced neuropeptide modulation (1, 8, 38, 46) or phenotypic switching (3, 20, 51). Our findings of a 75:25% distribution of nonpeptidergic to peptidergic fibers differ slightly from previous reports (55), perhaps due to extensive back-crossing onto a pure C57BL/6 background.…”

Section: Discussionmentioning

confidence: 99%

Early loss of peptidergic intraepidermal nerve fibers in an STZ-induced mouse model of insensate diabetic neuropathy

Johnson

Ryals

Wright

2008

Pain

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Peptidergic and nonpeptidergic nociceptive neurons represent parallel yet distinct pathways of pain transmission, but the functional consequences of such specificity are not fully understood. Here, we quantified the progression of peptidergic and nonpeptidergic axon loss within the epidermis in the setting of a dying-back neuropathy induced by diabetes. STZ-induced diabetic MrgD mice heterozygous for green fluorescent protein (GFP) in nonpeptidergic DRG neurons were evaluated for sensitivity to mechanical and noxious thermal and chemogenic stimuli 4 or 8 weeks post-STZ. Using GFP expression in conjunction with PGP9.5 staining, nonpeptidergic (PGP+/GFP+) and peptidergic (PGP+/GFP-) intraepidermal nerve fibers (IENFs) were quantified at each time point. At 4 weeks post-STZ, nonpeptidergic epidermal innervation remained unchanged while peptidergic innervation was reduced by 40.6% in diabetic mice. By 8 weeks post-STZ, both nonpeptidergic innervation and peptidergic innervation were reduced in diabetic mice by 34.1% and 43.8%, respectively, resulting in a 36.5% reduction in total epidermal IENFs. Behavioral deficits in mechanical, thermal, and chemogenic sensitivity were present 4 weeks post-STZ, concomitant with the reduction in peptidergic IENFs, but did not worsen over the next 4 weeks as nonpeptidergic fibers were lost, suggesting that the early reduction in peptidergic fibers may be an important driving force in the loss of cutaneous sensitivity. Furthermore, behavioral responses were correlated at the 4 week time point with peptidergic, but not nonpeptidergic, innervation. These results reveal that peptidergic and nonpeptidergic nociceptive neurons are differentially damaged by diabetes, and behavioral symptoms are more closely related to the losses in peptidergic epidermal fibers.

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“…CGRP is reduced in the heart, dorsal root ganglion and in primary sensory neurons of diabetic animal models [156][157][158]. Also, both CGRP and CGRP receptor expression were shown to be reduced in a diabetic cardiomyopathy model [159,160].…”

Section: Alteration Of Cgrp In Diabetesmentioning

confidence: 95%

Inflammatory and Angiogenic Abnormalities in Diabetic Wound Healing: Role of Neuropeptides and Therapeutic Perspectives

Tellechea¹

2012

TOCVJ

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Diabetic foot ulceration (DFU) is one of the most costly and debilitating complications of diabetes and is the leading cause of non-traumatic amputations, affecting 15% of the diabetic population. Impaired wound healing in diabetic patients without large-vessel disease has been attributed to microvascular dysfunction, neuropathy, and abnormal cellular and inflammatory responses. These abnormalities have been examined mainly in animal models although a few studies have been undertaken in diabetic patients. This review provides an overview of the inflammatory and vascular abnormalities in DFU and emphasises the role of angiogenic growth factors, endothelial progenitor cells (EPCs), and neuropeptides as mediators of wound healing and potential therapeutic agents for these chronic, non-healing ulcers.

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Characterization of the Proapoptotic Intracellular Mechanisms Induced by a Toxic Conformer of the Recombinant Human Prion Protein Fragment 90–231

Cited by 18 publications

References 43 publications

SP, CGRP changes in pyridoxine induced neuropathic dogs with nerve growth factor gene therapy

SP, CGRP changes in pyridoxine induced neuropathic dogs with nerve growth factor gene therapy

Early loss of peptidergic intraepidermal nerve fibers in an STZ-induced mouse model of insensate diabetic neuropathy

Inflammatory and Angiogenic Abnormalities in Diabetic Wound Healing: Role of Neuropeptides and Therapeutic Perspectives

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