The Saga of the Nerve Growth Factor

The following sections are included:

• FOREWORD

• CONTENTS

The following sections are included:

• DISCUSSION

• RÉSUMÉ

The following sections are included:

• INTRODUCTION

• MATERIAL

• THE ORIGIN OF THE NUCLEUS OF TERNI

• COMPARISON OF THE DEVELOPMENTAL PATTERN OE THE MOTOR COLUMN IN DIFFERENT REGIONS OF THE CORD
  • The preregional or general pattern in the motor column (4—4½ days of incubation)
  • Regional patterns

• ORIGIN OF THE PREGANGLIONIC SYSTEM IN THE SACRAL AND MEDULLARY LEVELS
  • Sacral column
  • The vagus complex

• DISCUSSION

• SUMMARY

• LITERATURE CITED

• PLATE 1

• PLATE 2

• PLATE 3

The following sections are included:

• MIGRATORY PATTERNS IN THE DEVELOPING NERVOUS SYSTEM
  • Migration from dorso-lateral and epibranchial placodes
  • Migratory movements in the central nervous system
  • Migration of the preganglionic viscero-motor column in birds and mammals
  • Migratory movements in the brain stem
  • Migratory movements in higher brain centers

• DEGENERATIVE PROCESSES IN THE DEVELOPING NERVOUS SYSTEM
  • Mass cell degeneration in the cervical level of the spinal cord
  • Degenerative processes in the cervical and thoracic spinal ganglia
  • Mass cell migration experimentally produced in the cervical spinal column
  • Mass cell degeneration experimentally produced in spinal ganglia and in the neural tube
  • Massive degeneration of the sympathetic nerve cells by an ‘Anti-Nerve Growth Factor'

• ACKNOWLEDGEMENTS

• SUMMARY

• REFERENCES

• DISCUSSION

The following sections are included:

• INTRODUCTION

• MATERIAL AND METHODS

• CHARACTERISTICS OF TUMOR GROWTH

• INVASION OF THE TUMORS BY NERVES
  • Period prior to nerve ingrowth
  • Ingrowth and distribution of fibers
  • Termination of nerve fibers (figs. 10 and 11)
  • Responses of sympathetic chain ganglia
  • Responses of the spinal ganglia
  • Observations on the spinal cord
  • Preliminary data on additional tumor innervation by peripheral sympathetic cells
  • The source of tumor nerves

• DISCUSSION

• SUMMARY

• LITERATURE CITED

• PLATE 1

• PLATE 2

• PLATE 3

• PLATE 4

• PLATE 5

The following sections are included:

• Extra-embryonic Transplants

• Peripheral Distribution of Visceral Nerve Fiber

• PLATE 1

• PLATE 2

• Concluding Remarks

• Bibliography

• Discussion of the Paper

Small pieces of mouse sarcoma 180 and 37 were grafted at the base of limb buds of two- to three-day chick embryos; they grew conspicuously and became invaded by sensory and sympathetic nerve fibers from the adjacent ganglia. The ganglia supplying nerves to the tumor are highly hyperplastic and hypertrophic. In addition, the sympathetic chain ganglia are enlarged and supernumerary ganglionic masses are formed. Sympathetic nerve fibers invade in large numbers adjacent viscera which normally receive little or no innervation in corresponding developmental stages. Agglomerations of sympathetic fibers protrude into the wall of the veins.

Transplantation of tumors 180 and 37 onto the allantoic membrane of four-day chick embryos produced similar effects on the sympathetic system. It was concluded that sarcomas 180 and 37 produce a diffusible growth stimulating agent which affects sympathetic nerve cells and fibers. The diffusible effect on the sensory ganglia remains to be investigated.

The effect of mouse sarcoma 180 on sensory and sympathetic ganglia of chick embryos was also tested in vitro. Sensory ganglia of seven-day chick embryos were explanted in close proximity to small pieces of sarcoma 180. After 24 hours, the ganglia show a conspicuous outgrowth of nerve fibers whose density is maximal on the side toward the tumor. Control cultures in which the same ganglia were combined with normal embryonic chick tissue (heart myoblasts) show only very few nerve fibers but a large number of migrating fibroblasts. In another control series, in which the same ganglia were confronted with normal embryonic mouse tissue (heart myoblasts) the nerve fiber outgrowth was more pronounced than in the chick tissue controls, but not comparable with the outgrowth called forth by the sarcoma. The effect increases during the following day. Sympathetic ganglia of chick embryos show a similar response to the tumor. Further experiments with these and other tumors are in progress.

The following sections are included:

• INTRODUCTION

• MATERIALS AND METHODS

• RESULTS
  • GROWTH OF ISOLATED SPINAL GANGLIA IN VITRO
  • EXPERIMENTS WITH SARCOMA 180
  • EXPERIMENTS WITH SARCOMA 37
  • EXPERIMENTS WITH SARCOMA 1
  • EXPERIMENTS WITH ADENOCARCINOMA DBEB
  • EXPERIMENTS WITH NEUROBLASTOMA C1300
  • CONTROL EXPERIMENTS WITH EMBRYONIC CHICKEN HEART
  • CONTROL EXPERIMENTS WITH HEART TISSUE OP EMBRYONIC, FETAL, OR NEW-BORN MICE

• DISCUSSION

• SUMMARY

• ACKNOWLEDGMENTS

• REFERENCES

The following sections are included:

• PLATE I

• PLATE II

The following sections are included:

• INTRODUCTION

• EXPERIMENTS IN VITRO

• EXPERIMENTS IN VIVO

• COMPARISON OF THE IN VIVO EFFECTS OF MOUSE SARCOMAS AND SNAKE VENOM

• CONCLUDING REMARKS AND SUMMARY

The following sections are included:

• PLATE I.—Microphotographs of sensory ganglia after 24 hours in vitro. Silver impregnation

• PLATE II

• PLATE III

The following sections are included:

• PLATE I.—Effects of rabbit antiserum against the purified protein of mouse salivary gland

• PLATE II.—Transverse sections of superior cervical ganglia in control (C) and experimental (E) animals, injected with rabbit antiserum to the salivary protein

The following sections are included:

• INTRODUCTION

• MATERIAL AND METHODS

• RESULTS
  • Sensory Nerve Cells
  • Sympathetic Nerve Cells

• DISCUSSION

• SUMMARY

• REFERENCES

The following sections are included:

• Growth Response of Nerve Cells to a Tumor Factor

• The Nerve Growth Factor: Its Nature, Biological Sources, and Effects

• Antiserum to the Nerve Growth Factor

• Reevaluation of Control Mechanisms of Nerve Cells by Extrinsic Agents

• Summary

• References and Notes

Purified nerve growth factor (NGF) induces a marked hypertrophy of the sympathetic chain ganglia when injected into newborn and adult mice. A 5-day treatment of newborn or adult mice with daily injections of NGF (20 μ/g body weight) results in both instances in a striking increase in wet weight of sympathetic ganglia. When examined at the electron microscope, the NGFtreated neurons appear very enlarged: the endoplasmic reticulum and free ribosomes are very abundant. The cytoplasmic area is filled with the interlacing bundles and threads of neurofilaments. This extraordinary production of neurofilaments and neurotubuli appears to be the most striking feature of the NGF-treated neurons.

The following sections are included:

• INTRODUCTION

• MATERIAL AND METHODS

• RESULTS
  • Control ganglia
  • Experimental ganglia: early lesions
  • Advanced lesions
  • Impaired RNA synthesis

• DISCUSSION

• SUMMARY

• ACKNOWLEDGEMENTS

• REFERENCES

The following sections are included:

• PRODUCTION AND ASSAY OF THE ANTISERUM TO THE NERVE GROWTH FACTOR

• MORPHOLOGIC CHANGES INDUCED BY THE ANTISERUM IN THE SUPERIOR CERVICAL GANGLION AND IN THE THORACIC CHAIN GANGLIA

• DIFFERENTIAL RESPONSE OF THE SYMPATHETIC GANGLIA OF NEWBORN MICE AND RATS TO THE ANTISERUM

• CONTENT, UPTAKE, AND METABOLISM OF NOREPINEPHRINE (NE) IN PERIPHERAL ORGANS OF IMMUNOSYMPATHECTOMIZED ANIMALS

• CONCLUDING REMARKS

• REFERENCES

Two different methods for a selective and complete destruction of the peripheral sympathetic nervous system are briefly presented. By using a specific antiserum to a Nerve Growth Factor, an « Immunosympathectomy » is obtained in newborn mammals. A « Chemical sympathectomy » can be induced by administration of a dopamine-analogue, 6-hydroxy-dopamine.

Deux méthodes différentes pour une destruction sélective et complète du système nerveux sympathique périphérique sont brièvement décrites.

The following sections are included:

• NGF Effect on Glucose Metabolism

• NGF Effect on Lipid Biosynthesis in Sensory and Sympathetic Ganglia

• NGF Effect on Protein Synthesis

• Effect of NGF on RNA Synthesis

• Effects of Specific Metabolic Inhibitors

• Discussion

• References

The following sections are included:

• The Nerve Growth Factor

• The Epidermal Growth Factor

• Production and Biological Significance of the Growth Factors

• Proceedings of the Royal Society of Medicine

• REFERENCES

The following sections are included:

• EARLY LITERATURE

• CHARACTERISTICS OF THE GROWTH RESPONSE OF SENSORY AND SYMPATHETIC NERVE CELLS IN THE LIVING ORGANISM
  • Sensory Ganglia
  • Sympathetic Ganglia

• CHARACTERISTICS OF THE IN VITRO GROWTH RESPONSE OF SENSORY AND SYMPATHETIC GANGLIA
  • Fibrillar Halo
  • Short- and Long-Term Cultures of Sympathetic Ganglia in Semisolid Media
  • NGF Effect on Dissociated Sensory and Sympathetic Nerve Cells in Liquid Media
  • NGF Effects on Sensory Nerve Cells at Ultrastructural Level

• BIOLOGICAL SOURCES OF NGF IN THE ORGANISM
  • Mouse Sarcomas: Characteristics of NGF-Releasing Neoplastic Cells
  • NGF Activity in Other Tumors, Tissues, and Body Fluids
  • NGF Activity in Snake Venom
  • Mouse Submaxillary Salivary Glands and Their Role in NGF Production

• GROWTH INHIBITION OF SYMPATHETIC NERVE CELLS BY ANTIBODIES TO NGF

• CHEMICAL PROPERTIES OF NGF
  • NGF From Snake Venom
  • NGF From Mouse Submaxillary Salivary Glands
  • Other Models Proposed for NGF Molecule

• METABOLIC EFFECTS OF NGF
  • Effect on Glucose Metabolism
  • Effect on Lipid Metabolism
  • Effect on Protein and RNA Synthesis

• NGF AND OTHER SPECIFIC GROWTH FACTORS
  • Epidermal Growth Factor
  • Erythropoietin-Stimulating Factor
  • Granulocytosis-Inducing Factor

• BIOLOGICAL SIGNIFICANCE OF NGF

• SUMMARY AND CONCLUDING REMARKS

• REFERENCES

Treatment of newborn rats with 10 λg/g of nerve growth factor for 10 days enhanced not only the growth but also the differentiation of neuroblasts in superior cervical ganglia. These morphological changes were accompanied by selective induction of tyrosine hydroxylase and dopamine β-hydroxylase (EC 1.14.2.1), whereas the total and specific activities of other enzymes involved in biosynthesis or metabolic degradation of norepinephrine rose only in proportion to t h e increase in volume of the sympathetic ganglia. There are remarkable similarities between this effect of nerve growth factor and the induction of trans-synaptic enzymes by increased activity of the sympathetic nervous system.

The following sections are included:

• RECENT STUDIES ON NGF TROPHIC AND PROTECTIVE EFFECTS ON IMMATURE SYMPATHETIC NERVE CELLS

• NGF NEUROTROPIC EFFECT

• NGF IN VITRO TRANSFORMING EFFECT OF PHEOCHROMOBLASTS IN SYMPATHETIC NERVE CELLS

• TRANSFORMATION OF IMMATURE CHROMAFFIN CELLS IN SYMPATHETIC NERVE CELLS IN RAT PUPS AFTER PRE- AND POSTNATAL NGF INJECTIONS

• TRANSFORMATION OF IMMATURE CHROMAFFIN CELLS IN NERVE CELLS IN CHICK EMBRYOS

• CONCLUDING REMARKS

• REFERENCES

The following sections are included:

• NGF Exerts a Trophic, Neurotropic and Differentiative Action

• NGF Action Is Not Confined to Neural Crest Derivatives

• The Mechanism of Action of NGF Is Still Largely Unknown

• mRNA for Mouse Salivary NGF Codes for a Much Larger NGF Precursor

• REFERENCES

The following sections are included:

• Light microscopic studies

• Fluorescence microscopic studies

• Electron microscopic studies

• Quantitative studies

The human nervous system is a vast network of several billion neurons, or nerve cells, endowed with the remarkable ability to receive, store and transmit information. In order to communicate with one another and with non-neuronal cells the neurons rely on the long extensions called axons, which are somewhat analogous to electrically conducting wires. Unlike wires, however, the axons are fluid-filled cylindrical structures that not only transmit electrical signals but also ferry nutrients and other essential substances to and from the cell body. Many basic questions remain to be answered about the mechanisms governing the formation of this intricate cellular network. How do the nerve cells differentiate into thousands of different types? How do their axons establish specific onnections (synapses) with other neurons and non-neuronal cells? And what is the nature of the chemical messages neurons send and receive once the synaptic connections are made?…

Previous work has shown that injections to neonatal mammals of a specific antiserum to the nerve growth factor (AS-NGF) produce irreversible destruction of sympathetic ganglia^1,2. The animals used in these studies were mice and rats. Because this treatment does not damage other nerve cells or produce adverse effects in other tissues and organs, the immunosympathectomized young and adult rodents do not exhibit—at gross inspection—somatic or behavioural differences compared with controls except for a marked ptosis³. Differences become apparent, however, when the treated rodents are submitted to physiological, pharmacological and behavioural tests⁴. We report here the dramatic effects that are produced by injections of purified antibodies to NGF in rat fetuses. A preliminary account of this work has already been presented^5,6, and similar effects have been demonstrated in another laboratory.

The present investigation was directed toward exploration of the spectrum of action of murine nerve growth factor (m-NGF) in peripheral cells and neurons in the central nervous system (CNS) of Xenopus laevis tadpoles. It was found that systemic m-NGF injections elicit growth and differentiative effects not only on sensory and sympathetic nerve cells but also on several populations in the CNS. The finding that aminergic and peptidergic neurons in brain centers are highly receptive to m-NGF activity provides evidence for the broad spectrum of action of this molecule in lower vertebrates and calls for a systematic search for these and other putative target cells in the CNS of higher vertebrates.

Intraspecific fighting induced by 6-8 weeks of social isolation results in massive release of nerve growth factor (NGF) into the bloodstream of adult male mice. The amount of circulating NGF is highly correlated with the number of fighting episodes. Biological, radioimmunological, immunohistochemical, and ultrastructural studies show that NGF is discharged from the salivary gland into the blood within minutes after fighting and reaches the highest level 3-4 hr later. Adrenergic innervation of the salivary gland or drenalectomy does not abolish the NGF release. Corticotropic hormones do not induce NGF increase in the blood. Daily administrations of highly purified NGF (3 λg per g of body weight) result in a considerable increase in the volume of adrenal glands. These findings are unequivocable evidence for a physiological role of the mouse salivary glands as a major source of blood NGF.

The effects of intermale aggressive behavior induced by social isolation on the level of nerve growth factor (NGF) mRNA and protein were investigated in centra] and peripheral mouse tissues. A large increase in NGF mRNA and protein was observed in hypothalamus, with no changes in cerebral cortex, hippocampus, and cerebellum. No change in NGF mRNA levels was found in heart, spleen, vas deferens, and submaxillary salivary gland. The cellular localization of NGF mRNA in the central nervous system was investigated by in situ hybridization. Numerous nerve cells were specifically labeled in preoptic and ventrolateral nuclei of the hypothalamus, as well as in the cornu ammonis region of the hippocampus and throughout all layers of the cerebral cortex, with the highest oncentration in layer III. The present results firmly establish that nerve cells constitute the major source of NGF in the brain. They also open the way to understanding the regulation of NGF biosynthesis in the central nervous system.

The following sections are included:

• Mapping and biological response of NGF target cells

• Evolutionary conservation of NGF and its receptor

• NGF's mechanism of action

• The role of the submandibular gland and other large NGF sources

• NGF, PGFsandoncogenes

• Final remarks and perspectives

• Acknowledgements

• Selected references

Embryogenesis is in some way a model system. It has always been distinguished by the exactitude, even punctilio, of its anatomical descriptions. An experiment by one of the great masters of embryology could be made the text of a discourse on scientific method. But something is wrong, or has been wrong. There is no theory of development in the sense in which Mendelism is a theory that accounts for the results of breeding experiments. There has therefore been little sense of progression or timeliness about embryological research. Of many papers delivered at embryological meetings, however good they may be in themselves, one too often feels that they might have been delivered 5 years beforehand without making anyone much the wiser, or deferred for 5 years without making anyone conscious of a great loss.—P. MEDAWAR

A major shift in nerve growth factor (NGF) studies has occurred with the realization that the spectrum of action of this protein molecule is not restricted, as previously believed, to enhancing differentiative processes of two peripheral neuronal cell lines (the sensory and sympathetic neurons), but extends also to several other neuronal and non-neuronal cell types. The newly detected NGF-responsive cells belong to the hemopoietic-immune system, to the cholinergic system of the basal forebrain nuclei, and to other cell populations of the central nervous system involved in euroendocrine functions. It is the object of this article to report on findings that project a much wider role for this protein molecule than initially had been envisaged. Additional evidence promoting this concept came from results of other investigations showing that NGF synthesis in some hypothalamic nuclei, and its level—in the bloodstream of mice displaying aggressive behavior, are markedly increased, as compared to controls. These and previous findings support the hypothesis that this protein molecule may exert a modulatory role on neuro-immunoendocrine functions of vital importance in the regulation of homeostatic processes.

Please refer to full text.

Cytokines regulate nerve growth factor (NGF) synthesis during inflammatory processes. Since cytokines are also involved in the inflammatory processes of autoimmune rheumatic diseases, we examined levels of NGF in patients with rheumatoid or other types of chronic arthritis. NGF was present in the synovial fluid and synovium of patients with chronic arthritis, but was undetectable in control fluids. We conclude that NGF might be involved in the pathogenesis of arthritis.

Recent studies effected by our Institute indicate that various forms of human arthritis express both immunohistochemically and biologically active nerve growth factor (NGF) in the ynovium. In the present study, we used a model of carrageenan-induced arthritis to further evaluate the effects of joint inflammation on NGF level. These studies showed that experimentally-induced arthritis in rats caused a significant increase in NGF in the perivascular area of the synovium. We also showed that injection into the synovium of purified NGF did not cause inflammation per se and that the destruction of peripheral sympathetic innervation significantly reduced both the inflammation and the level of NGF following carrageenan injection.

We describe the measurement of β-nerve growth factor (NGF) content in cerebrospinal fluid (CSF) from multiple sclerosis (MS) patients compared with CSF from age-matched normal subjects using a specific sandwich immunoassay (ELISA). During acute attacks patients exhibit a significant increase of NGF content compared to controls. In contrast during remission the mean NGF levels in CSF markedly decrease. These results strongly indicate that increased NGF production in CSF is a characteristic feature of the MS inflammatory response.

We have recently reported that nerve growth factor (NGF) increases in the synovium of patients affected by arthritis, as well as in animal models. We report here that the synovium of transgenic arthritic mice xpressing human tumour necrosis factor (TNF) contains numerous mast cells (MC) and that their appearance is a henomenon which was correlated to the local increase in NGF level. These findings provide further evidence that NGF plays a role in inflammation and suggest a functional link between NGF and MC.

We have recently reported that nerve growth factor (NGF) increases in the synovium of patients affected by rheumatoid arthritis and in the synovium of pharmacologically-induced arthritis in animal models. In the present study, we demonstrate that arthritic transgenic mice which carry and express the human TNF gene (Tgl97) also express elevated levels of NGF, and that subcutaneous injection of NGF-antibodies attenuates the loss of body weight caused by the developement of disease in these mice. Along with our previous findings,which show an increase in the level of NGF during the acute phase of other autoimmune diseases, these results suggest a role of NGF in these pathologies. The functional significance of NGF in rheumatoid arthritis (RA) is currently under study.

USING a specific enzyme-linked immunosorbent assay (ELISA) for human nerve growth factor (NGF), serum levels in patients with systemic lupus erythematosus (SLE) were measured. We found a consistent increase in NGF levels in SLE patients compared with controls. A good correlation exists between serum NGF level and severity of clinical manifestation. We hypothesize that NGF might play a role in the pathogenesis of autoimmune disorders such as SLE.

THE presence of biologically active nerve growth factor (NGF) in the peripheral circulation of women during pregnancy, labour and lactation was investigated. Using a sensitive immunoenzymatic assay (ELISA), we found an approximately five-fold increase in plasma NGF levels during labour and lactation compared with the concentrations found at the term of gestation or in control healthy women. Since labour and lactation are characterized by activation of the hypothalamo-pituitary-adrenal axis and by high plasma levels of the neurohypophyseal hormone oxytocin, and since the intravenous injection of oxytocin in female rats causes a 176% increase in the hypothalamic levels of NGF, it is possible that the increased amount of circulating NGF is correlated with one or both of these events.

Evidence is provided here supporting the existence of a novel autacoid mechanism negatively modulating mast cell behaviour in response to noxious stimuli in vivo; hence, the denomination “autacoid local inflammation antagonism” (ALIA). In particular, as lipid amides of the iV-acylethanolamine type have been reported to accumulate in tissues in degenerative inflammatory conditions, we examined whether these Nacylated lipids could exert regulatory effects on mast cell activation in vivo. The results reported show that both long- and short-chain N-acylethanolamines, when systemically administered, are effective in reducing mast cell degranulation induced by local injection of substance P in the ear pinna of developing rats. These and other data suggest that the endogenous production of N-acylethanolamines may constitute a local autocrine/paracrine response for the negative feedback control of mast cell responses to various activating signals. Such a process may be of physio-pathological relevance in the regulation of functional neuroimmune- mast cell interactions.

Mast cells and nerve growth factor (NGF) have both been reported to be involved in neuroimmune interactions and tissue inflammation. In many peripheral tissues, mast cells interact with the innervating fibers. Changes in the behaviors of both of these elements occur after tissue injury/inflammation. As such conditions are typically associated with rapid mast cell activation and NGF accumulation in inflammatory exudates, we hypothesized that mast cells may be capable of producing NGF. Here we report that (i) NGF mRNA is expressed in adult rat peritoneal mast cells; (ii) anti-NGF antibodies clearly stain vesicular compartments of purified mast cells and mast cells in histological sections of adult rodent mesenchymal tissues; and (iii) medium conditioned by peritoneal mast cells contains biologically active NGF. Mast cells thus represent a newly recognized source of NGF. The known actions of NGF on peripheral nerve fibers and immune cells suggest that mast cell-derived NGF may control adaptive/ reactive responses of the nervous and immune systems toward noxious tissue perturbations. Conversely, alterations in normal mast cell behaviors may provoke maladaptive neuroimmune tissue responses whose consequences could have profound implications in inflammatory disease states, including those of an autoimmune nature.

The initiation of a humoral immune response to a foreign antigen is a complex biologic process involving the interaction of many cell ypes and their secreted products. Autoimmune diseases, which are characterized by an abnormal activation of the immune system, probably result from the failure of normal self-tolerance mechanisms. The etiology of such illnesses, however, is far from being understood.While there have been extensive studies on the participation of the immune and endocrine systems in autoimmune iseases, few have dealt with nervous system-mediated immunoregulation in such situations. Evidence continues to grow suggesting that nerve growth factor (NGF), first identifiedfor its activity in promoting the growth and differentiation of sensory and sympathetic neurons, may exert a modulatory role on neuroimmunoendocrine functions of vital importance in the regulation of homeostatic processes. Newly detected NGF-responsive cells belong to the hemopoietic-immune system and to populations in the brain involved in neuroendocrine functions. NGF levels are elevated in a number of autoimmune states, along with increased accumulation of mast cells. NGF and mast cells both appear to be involved in neuroimmune interactions and tissue inflammation. Moreover, mast cells themselves synthesize, store, and release NGF, proposing that alterations in normal mast cell behaviors may provoke maladaptive neuroimmune tissue responses whose consequences could have profound implications in inflammatory disease states, including those of an autoimmune nature. This review focuses on these cellular events and presents a working model which attempts to explain the close interrelationships of the neuroendocrinoimmune triade via a modulatory action of NGF.

The following sections are included:

• NGF effects in neurogenesis

• Phylogenetic features of the NGF receptor system and its target cells

• The NGF molecule and its gene

• Mechanisms of action

• NGF as a paradigm of neuronal and nonneuronal growth factors

• A role for NGF in nervous, endocrine, and immune systems

• Further reading

Nerve growth factor (NGF), initially characterized for its survival and differentiating actions on embryonic sensory and sympathetic neurons, is now known to display a greatly extended spectrum of biological functions. NGF exerts a profound modulatory role on sensory nociceptive nerve physiology during adulthood which appears to correlate with hyperalgesic phenomena occurring in tissue inflammation. Other newly detected NGF-responsive cells belong to the hematopoietic-immune and neuroendocrine systems. In particular, mast cells and NGF both appear to be involved in neuroimmune interactions and tissue inflammation, with NGF acting as a general “alert” molecule capable of recruiting and priming both local tissue and systemic defense processes following stressful events. NGF can thus be viewed as a multifactorial mediator modulating neuroimmune-endocrine functions of vital importance to the regulation of homeostatic interactions, with potential involvement in pathological processes deriving from dysregulation of either local or systemic homeostatic balances.

The following sections are included:

• BIBLIOGRAPHY