Detection of brain-derived neurotrophic factor-like activity in fibroblasts and Schwann cells: Inhibition by antibodies to NGF

doi:10.1016/0896-6273(91)90265-2

Neuron

Volume 7, Issue 2, August 1991, Pages 265-275

https://doi.org/10.1016/0896-6273(91)90265-2 Get rights and content

Abstract

mRNA coding for brain-derived neurotrophic factor (BDNF) has been detected in cultured L929 fibroblasts, rat dermal fibroblasts, and sciatic nerve Schwann cells, as well as in rat skin. Medium conditioned by cultured fibroblasts and Schwann cells also stimulates neurite growth from retinal explants and promotes the survival in culture of BDNF-responsive sensory neurons; biological activity is abolished by antibodies raised against NGF. These results suggest that molecules with BDNF-like activity may be produced by cells in the peripheral nervous system and that the BDNF-like activity in fibroblasts and Schwann cells is derived from molecules immunologically related to NGF. In support of this concept, antibodies against NGF have been found to reduce the biological activity of recombinant BDNF in culture and to cross-react with BDNF on Western blots.

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Oligodendrocyte (OL) replacement is a promising treatment strategy for spinal cord injury (SCI). However, the poor survival of transplanted OLs or their precursors and inhibition of axonal regeneration are two major challenges with this approach. Our previous study showed that Schwann cells (SCs) promoted survival, proliferation, and migration of transplanted OL progenitor cells (OPCs) and neurological recovery. Remyelination is an important basis for functional recovery following spinal cord injury. It has been reported that myelin gene regulatory factor (MRF), a transcriptional regulator which specifically is expressed in postmitotic OLs within the CNS, is essential for OL maturation and CNS myelination. In the present study, we investigated whether co-transplantation of MRF-overexpressing OPCs (MRF-OPCs) and SCs could improve functional recovery in a rat model of contusional SCI. MRF overexpression had no effect on OPC survival or migration, but stimulated the differentiation of OPCs both in vitro and in vivo. Co-transplantation of MRF-OPCs and SCs increased myelination and tissue repair after SCI, leading to the recovery of neurological function. These results indicate that co-transplantation of MRF-OPCs and SCs may be an effective treatment strategy for SCI.
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Importantly, this study confirms that glial scar formation is a major impediment for axonal sprouting after spinal cord injury, and emphasizes the importance of serotonergic innervation for locomotor function. Moreover we show a significant additive effect of a combinatorial approach to axonal regeneration in the injured spinal cord.
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Neuron

ArticleDetection of brain-derived neurotrophic factor-like activity in fibroblasts and Schwann cells: Inhibition by antibodies to NGF

Abstract

Exp. Cell Res.

Neuron

Brain Res.

Trends Neurosci.

Trends Biochem. Sci.

Dev. Biol.

Brain Res.

Dev. Biol.

Neuron

Neuron

Brain Res.

Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines

J. Neurosci.

Cellular localization of nerve growth factor synthesis by in situ hybridization

EMBO J.

Sensory neurons in culture: changing requirements for survival factors during development

Purification of a new neurotrophic factor from mammalian brain

EMBO J.

The response of chick sensory neurons to brain-derived neurotrophic factor

J. Neurosci.

Different factors from the central nervous system and periphery regulate the survival of sensory neurones

Nature

The heparin-binding domain of laminin is responsible for its effects on neurite outgrowth and neuronal survival

EMBO J.

Purification of a fibroblast growth factor from bovine pituitary

J. Biol. Chem.

The nerve growth factor: biochemistry, synthesis and mechanism of action

Annu. Rev. Neurosci.

Comparison of 7S nerve growth factor and nerve growth factor I from mouse submandibular gland

Biochemistry

Relationship between levels of nerve growth factor (NGF) and its messenger RNA in sympathetic ganglia and peripheral target tissues

EMBO J.

Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration and regeneration: role of macrophages

Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family

Nature

Article
Detection of brain-derived neurotrophic factor-like activity in fibroblasts and Schwann cells: Inhibition by antibodies to NGF