Expression of growth‐associated protein‐43 kD in Schwann cells is regulated by axon‐Schwann cell interactions and cAMP

Scherer, Steven S.; Xu, Yi; Roling, D.; Wrabetz, Lawrence; Feltri, M. Laura; Kamholz, John

doi:10.1002/jnr.490380510

Cited by 59 publications

(37 citation statements)

References 68 publications

(93 reference statements)

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“…29 Schwann cells are also known to express GAP43 after nerve transaction. 30 Compatible with these findings, we observed GAP43-positive cells within the infarcted site. Some of these cells are stromal cells that are often found in the infarcted myocardia.…”

Section: Source Of Mrnasupporting

confidence: 84%

Mechanisms of Cardiac Nerve Sprouting After Myocardial Infarction in Dogs

Zhou

Chen

Miyauchi

et al. 2004

Circulation Research

302

291

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Abstract-Cardiac nerve sprouting and sympathetic hyperinnervation after myocardial infarction (MI) both contribute to arrhythmogenesis and sudden death. However, the mechanisms responsible for nerve sprouting after MI are unclear. The expression of nerve growth factor (NGF), growth associated protein 43 (GAP43), and other nerve markers were studied at the infarcted site, the noninfarcted left ventricle free wall (LVFW), and the left stellate ganglion (LSG) at several time points (30 minutes to 1 month) after MI. Transcardiac (difference between coronary sinus and aorta) NGF levels were also assayed. Acute MI resulted in the immediate elevation of the transcardiac NGF concentration within 3.5 hours after MI, followed by the upregulation of cardiac NGF and GAP43 expression, which was earlier and more pronounced at the infarcted site than the noninfarcted LVFW. However, cardiac nerve sprouting and sympathetic hyperinnervation were more pronounced in the noninfarcted than the infarcted LVFW site and peaked at 1 week after MI. The NGF and GAP43 protein levels significantly increased in the LSG from 3 days (PϽ0.01 for all) after MI, without a concomitant increase in mRNA. There was persistent elevation of NGF levels in aorta and coronary sinus within 1 month after MI. We conclude MI results in immediate local NGF release, followed by upregulation of NGF and GAP43 expression at the infarcted site. NGF and GAP43 are transported retrogradely to LSG, which triggers nerve sprouting at the noninfarcted LVFW. A rapid and persistent upregulation of NGF and GAP43 expression at the infarcted site underlies the mechanisms of cardiac nerve sprouting after MI. Key Words: nerve growth factor Ⅲ nerve sprouting Ⅲ sympathetic nerve Ⅲ ventricular arrhythmia W e previously demonstrated that heterogeneous cardiac nerve sprouting and sympathetic hyperinnervation play important roles in arrhythmogenesis and sudden cardiac death in both human patients and animal models of myocardial infarction (MI). 1-6 However, the mechanisms and time course of nerve sprouting after MI are unclear. Nerve growth factor (NGF) is a neurotrophin that supports the survival and differentiation of sympathetic neurons and enhances target innervation. 7,8 NGF also regulates the synthesis of neurofilament and tubulin proteins, promotes Schwann cell migration, 9 modulates synaptic transmission between sympathetic neurons and cardiac myocytes, 10 and increases the half-life of growth associated protein-43 (GAP43). 11 Overexpression of NGF within the heart of transgenic mice causes hyperinnervation. 12 Peripheral nerve injury results in increased local NGF expression, which facilitates nerve regeneration. 13 It is possible that increased NGF expression also underlies the mechanisms of cardiac nerve sprouting after ischemic injury and MI. In the present study, we sampled blood and harvested tissues from the left ventricle and from the left stellate ganglion at different time points after experimental canine MI. NGF expression and the magnitude of cardiac nerve sprouting...

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Section: Source Of Mrnasupporting

confidence: 84%

Mechanisms of Cardiac Nerve Sprouting After Myocardial Infarction in Dogs

Zhou

Chen

Miyauchi

et al. 2004

Circulation Research

302

291

View full text Add to dashboard Cite

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“…The GAP-43 immunopositive processes that did not colocalize with neurofilament may be host Schwann cells ( Fig. 1 C and D), which express GAP-43 (38,39) and have been shown to migrate into the damaged spinal cord in several models of SCI (40)(41)(42)(43)(44)(45). Because OECs and Schwann cells share many antigenic and phenotypic properties (reviewed in refs.…”

Section: Resultsmentioning

confidence: 98%

LacZ -expressing olfactory ensheathing cells do not associate with myelinated axons after implantation into the compressed spinal cord

Boyd

Lee

Skihar

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Studies have shown that implanting olfactory ensheathing cells (OECs) may be a promising therapeutic strategy to promote functional recovery after spinal cord injury. Several fundamental questions remain, however, regarding their in vivo interactions in the damaged spinal cord. We have induced a clip compression injury at the T10 level of the spinal cord in adult rats. After a delay of 1 week, OECs isolated from embryonic day 18 rats were implanted into the cystic cavity that had formed at the site of injury. Before implantation, OECs were infected with a LacZ-expressing retrovirus. At 3 weeks after implantation, LacZ-expressing OECs survived the implantation procedure and remained localized to the cystic cavity. At the electron microscopic level, the cystic cavity had clusters of LacZ-expressing OECs and numerous Schwann cells lacking LacZ expression. Although labeled OECs made no direct contact with axons, unlabeled Schwann cells were associated with either a single myelinated axon or multiple unmyelinated axons. Positively labeled OEC processes often enveloped multiple Schwann cellaxon units. These observations suggest that the role of OECs as the primary mediators of the beneficial effects on axon growth, myelination, and functional recovery after spinal cord injury may require re-evaluation.

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“…Previous results suggest that Gpr126 functions to elevate cAMP levels in promyelinating Schwann cells prior to myelination (Monk et al, 2009). cAMP elevation in postmitotic Schwann cells is thought to downregulate premyelinating signals and upregulate myelinating signals Monuki et al, 1989;Scherer et al, 1994). It is possible that non-myelinating Schwann cells also require elevation of cAMP levels in order to differentiate.…”

Section: Research Articlementioning

confidence: 99%

Gpr126 is essential for peripheral nerve development and myelination in mammals

et al. 2011

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SUMMARYIn peripheral nerves, Schwann cells form the myelin sheath that insulates axons and allows rapid propagation of action potentials. Although a number of regulators of Schwann cell development are known, the signaling pathways that control myelination are incompletely understood. In this study, we show that Gpr126 is essential for myelination and other aspects of peripheral nerve development in mammals. A mutation in Gpr126 causes a severe congenital hypomyelinating peripheral neuropathy in mice, and expression of differentiated Schwann cell markers, including Pou3f1, Egr2, myelin protein zero and myelin basic protein, is reduced. Ultrastructural studies of Gpr126-/-mice showed that axonal sorting by Schwann cells is delayed, Remak bundles (non-myelinating Schwann cells associated with small caliber axons) are not observed, and Schwann cells are ultimately arrested at the promyelinating stage. Additionally, ectopic perineurial fibroblasts form aberrant fascicles throughout the endoneurium of the mutant sciatic nerve. This analysis shows that Gpr126 is required for Schwann cell myelination in mammals, and defines new roles for Gpr126 in axonal sorting, formation of mature non-myelinating Schwann cells and organization of the perineurium.

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Expression of growth‐associated protein‐43 kD in Schwann cells is regulated by axon‐Schwann cell interactions and cAMP

Cited by 59 publications

References 68 publications

Mechanisms of Cardiac Nerve Sprouting After Myocardial Infarction in Dogs

Mechanisms of Cardiac Nerve Sprouting After Myocardial Infarction in Dogs

LacZ -expressing olfactory ensheathing cells do not associate with myelinated axons after implantation into the compressed spinal cord

Gpr126 is essential for peripheral nerve development and myelination in mammals

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