Submandibular glands, nerve growth factor and neuroinflammatory responses in rodents

Structural, biochemical, and pharmacological studies have provided numerous insights into the role of rodent submandibular glands in a variety of physiopathological functions. In this review we briefly highlight past and present findings published by our group and others regarding the role of rodent submandibular glands and nerve growth factor in inflammatory events. Accordingly, the role of mouse salivary glands and nerve growth factor in neuroinflammatory responses, body temperature and parasitic infection are discussed, and potential future lines of studies aimed at elucidating their physiopathological roles are suggested.Biomedical Reviews 1998; 9: 93-99

Nerve growth factor: basic findings and clinical trials

The nerve growth factor is the first-discovered and best-characterized member of the family of neurotrophins. In the introduction of this article we present a brief biographic view of past and present studies of Rita Levi-Montalcini on nerve growth factor: Further, the article focuses on pleiotropic activities of nerve growth factor, exerting on various cell types, including cells of nervous, immune and endocrine system. Implications of these actions of nerve growth factor in the pathogenesis of neurological diseases, autoimmune-inflammatory diseases, allergic diseases, lymphoproliferative diseases, atherosclerotic cardiovascular disease, and neurotrophic corneal ulcers are outlined.Biomedical Reviews 1999; 10: 3-14

Electroacupuncture counteracts the development of thermal hyperalgesia and the alteration of nerve growth factor and sensory neuromodulators induced by streptozotocin in adult rats.

AIMS/HYPOTHESIS: Diabetes is considered the leading cause of neuropathies in developed countries. Dysfunction of nerve growth factor (NGF) production and/or utilisation may lead to the establishment of diabetic neuropathies. Electroacupuncture has been proved effective in the treatment of human neuropathic pain as well as in modulating NGF production/activity. We aimed at using electroacupuncture to correct the development of thermal hyperalgesia and the tissue alteration of NGF and sensory neuromodulators in a rat model of type 1 diabetes. METHODS: Adult rats were injected with streptozotocin to induce diabetes and subsequently treated with low-frequency electroacupuncture for 3 weeks. Variation in thermal sensitivity was studied during the experimental course. Hindpaw skin and spinal cord protein content of NGF, NGF receptor tyrosine kinase A (TrkA), substance P (SP), transient receptor potential vanilloid 1 (TRPV1) receptor and glutamic acid decarboxylase-67 (GAD-67) were measured after electroacupuncture treatments. The skin and spinal cord cellular distribution of TrkA was analysed to explore NGF signalling. RESULTS: Early after streptozotocin treatment, thermal hyperalgesia developed that was corrected by electroacupuncture. The parallel increases in NGF and TrkA in the spinal cord were counteracted by electroacupuncture. Streptozotocin also induced variation in skin/spinal TrkA phosphorylation, increases in skin SP and spinal TRPV1 and a decrease in spinal GAD-67. These changes were counteracted by electroacupuncture. CONCLUSIONS/INTERPRETATION: Our results point to the potential of electroacupuncture as a supportive therapy for the treatment of diabetic neuropathies. The efficacy of electroacupuncture might depend on its actions on spinal/peripheral NGF synthesis/utilisation and normalisation of the levels of several sensory neuromodulators

Rita Levi-Montalcini and the nerve growth factor

With this special volume of Biomedical Reviews we bring to you an update of Nerve Growth Factor in Health and Disease.Biomedical Reviews 1999; 10: 1-2

Neurolipidology: interactions of nerves, neurotrophic factors, and lipids

Here we highlight current data of the involvement of cholesterol, lipoproteins and lipoprotein receptors in the neuronal development and of neurotrophic factors in the lipid and glucose metabolism. We term these interactions neurolipidology. And argue that in addition to its implication in neurodegenerative diseases such as Alzheimer`s disease, neurolipidology may have wide-ranging potential within a variety of nonneuronal fields, including cardiovascular disease, particularly, atherosclerosis and related disorders.Biomedical Reviews 1999; 10: 111-113

Homage to Rita Levi-Montalcini, the queen of modern neuroscience

The first cell growth factor, nerve growth factor (NGF), was discovered by Rita Levi-Montalcini (RLM) in the early 1950's in Washington University in Saint Louis, Missouri, USA. Originally identified as neurite outgrowth-stimulating factor, later studies revealed that non-neuronal cells, including immune cells, endothelial cells, cardiomyocytes, pancreatic beta cells, prostate epithelial cells and adipose tissue cells, are also targets for and/or sources of NGF. Nerve growth factor is well recognized at present to mediate multiple biological phenomena, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. Consequently, NGF and other members of the neurotrophin family are implicated in the pathogenesis of a large spectrum of neuronal and non-neuronal diseases, ranging from Alzheimer's and other neurodegenerative diseases to atherosclerosis and other cardiometabolic diseases. Recent studies demonstrated the therapeutic potentials of NGF in these diseases including ocular and cutaneous diseases. Whereas NGF TrkA receptor antagonists emerged as novel drugs for pain, prostate and breast cancer, and urinary bladder syndromes. Here we briefly describe (i) the "unpredictable" ideogenesis of the discovery of NGF, and (ii) our scientific and human experience working in RML's laboratory for 15 years (GNC) and over 40 years (LA).Biomedical Reviews 2012; 23: 1-7

Effect of electro-acupuncture on ovarian expression of α (1)- and β (2)-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries

BACKGROUND: Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz) electro-acupuncture (EA) has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO. METHODS: In the present study, we further tested the hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow in rats with PCO, induced by a single i.m. injection of EV, by investigating the mRNA expression, the amount and distribution of proteins of α1a-, α1b-, α1d-, and β2-adrenoceptors (ARs), as well as the low-affinity neurotrophin receptor (p75NTR). RESULTS: It was found that EV injection results in significantly higher mRNA expression of ovarian α1b- and α1d-AR in PCO rats compared to control rats. The p75NTR and β2-ARs mRNA expression were unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower expression of β2-ARs mRNA expression in PCO rats. The p75NTR mRNA was unaffected in both PCO and control rats. PCO ovaries displayed significantly higher amount of protein of α1a-, α1b- and α1d-ARs, and of p75NTR, compared to control rats, that were all counteracted by repeated low-frequency EA treatments, except for α1b-AR. CONCLUSION: The present study shows that EA normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action. Our data indicate a possible role of EA in the regulation of ovarian responsiveness to sympathetic inputs and depict a possible complementary therapeutic approach to overcoming sympathetic-related anovulation in women with PCOS

Nerve growth factor, mast cells and arthritis

Nerve growth factor is a well-characterized neurotrophic protein required for the survival and differentiation of a variety of neuronal cell types both in the peripheral and central nervous systems. Recent studies indicate that nerve growth factor also plays a role in cells originating in the immune system, since it is synthesized by cells of immune system lineage and its level increases during inflammatory responses. Moreover, it has been shown that cytokines such as interleukin 1β and tumor necrosis factor-α are potent inducers of nerve growth factor secretion. These studies were recently confirmed and extended by demonstrating that cells normally present in inflammatory tissues, such as mast cells and lymphocytes, express nerve growth factor receptors and are receptive to the action of nerve growth factor. The aim of the present review is to outline the current understanding of mast cells and nerve growth factor in autoimmune diseases and particularly in arthritis.Biomedical Reviews 1995; 4: 7-14

NGF and NGF-receptor expression of cultured immortalized human corneal endothelial cells

Several growth factors, including nerve growth factor (NGF) and vascular endothelial growth factor (VEGF), play an important role in the homeostasis of the ocular surface. The involvement of both these growth factors in the pathophysiology of intraocular tissues has been extensively investigated. Despite the expression of NGF receptors by corneal endothelium, to date the role of NGF on the endothelial cell remains to be determined. Using a clonal cell line of human corneal endothelial cells, the aim of this study was to investigate the expression of the NGF-receptor and the potential partnership of NGF and VEGF in maintaining cell viability in vitro