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Biomedical subjects

U Otten

Publications and source records attributed to U Otten.

At least 91 records · Page 5Linked to original sources
PubMed1988

Effect of bilateral decortication on nerve growth factor content in basal nucleus and neostriatum of adult rat brain.

The content of nerve growth factor (NGF) was measured by a sensitive two-site enzyme-linked immunosorbent assay in the basal nucleus and neostriatum at various times following bilateral suction lesions of the cerebral neocortex in adult rats. At 14 and 29 postlesion days, NGF levels in basal nucleus were significantly elevated by 270 and 126%, respectively. In addition, 29 days after cortical lesions, NGF content in the neostriatum was increased 145% above controls. Thus, enhanced NGF production occurs in both basal nucleus and neostriatum of adult rats in response to antero- and/or retrograde neuronal degeneration.

Animals↗
PubMed1988

Neuronotrophic factors released by C6 glioma cells.

Glial cells have been shown previously to release factors that promote survival of central and peripheral neurons [neuronotrophic factors (NTFs)]. We have investigated the release of NTFs by C6 cells, a rat glioma cell line, under different modes of conditioning. Media conditioned in the presence or absence of serum [C6 cell conditioned media (C6CMs)] were analyzed using biological, biochemical, and immunological assays. We report that (a) nuclear and cytoskeletal proteins were not present in C6CMs, indicating that C6CM proteins result from release by C6 cells rather than from cell death; (b) C6CM contained 1-3 micrograms protein/ml, corresponding to a secretion rate of about 0.5 pg protein per cell and day; (c) C6CM contained the neurite-promoting factor laminin and low amounts of nerve growth factor; (d) the presence of fetal calf serum in the culture medium was essential for synthesis and release of NTFs; and (e) our C6CM contained at least three NTFs differing by their temporal secretory patterns and three NTFs differing by biochemical properties, indicating that C6 cells produce and secrete six different NTFs. Within these, nerve growth factor seems to be the only established NTF.

Animals↗
PubMed1988

Epidermal growth factor content of submandibular glands is increased in rats with experimentally induced gastric lesions.

Occurrence and growth-promoting effect suggest that epidermal growth factor (EGF) is involved in the maintenance of the gastrointestinal mucosa. The aim of this study was to ascertain whether rats with gastric lesions, induced by cold-water stress, ethanol, or indomethacin, have altered EGF levels in their gastrointestinal tract compared with controls. For this purpose we established a solid-phase enzyme immunoassay and measured the amount of immunoreactive EGF (IR-EGF) in extracts of the submandibular gland, stomach, duodenum, jejunum, ileum, and colon. In the submandibular glands of control rats the IR-EGF content was 100-400 times higher than in the gastrointestinal tract. In animals with experimentally induced ulcer the IR-EGF content was increased in the submandibular glands (1480 versus 423 ng/g), duodenum (11.4 versus 5.8 ng/g), and colon (4.1 versus 1 ng/g), whereas no change was observed in the stomach and jejunum. When the formation of lesions was prevented by omeprazole (stress) or prostaglandin E2 (ethanol and indomethacin), the IR-EGF increase in submandibular glands and duodenum was abolished. This indicates that mechanisms regulating the synthesis and secretion of submandibular EGF might be of importance in the development of gastric and duodenal ulcers.

Animals↗
PubMed1987

Substance P modulates the release of locally synthesized nerve growth factor from rat saphenous nerve neuroma.

In saphenous nerve neuromata of adult rats a long-term increase of immunoreactive nerve growth factor (irNGF) was detected after nerve transection. The occurrence of messenger RNA encoding NGF (NGF mRNA) in these proximal nerve stumps indicates local biosynthesis of NGF. In situ superfusion of neuromata revealed a constant release of irNGF which was significantly reduced by substance P (SP) but not affected by calcitonin gene related peptide (CGRP). We therefore suggest that SP may modulate the availability of NGF in the microenvironment of the regenerating nerve fiber endings.

Animals↗
PubMed1987

An enzyme-linked immunoassay for nerve growth factor (NGF): a tool for studying regulatory mechanisms involved in NGF production in brain and in peripheral tissues.

A sensitive enzyme-linked immunosorbent assay (ELISA) for nerve growth factor (NGF) has been developed. The sensitivity of this assay (0.1 pg/well) permits the quantification of endogenous immunoreactive NGF in the peripheral nervous system and the CNS. Studies on the regulatory mechanisms involved in NGF production indicate that, in addition to neurally mediated mechanisms, other stimuli, e.g., inflammation, significantly contribute to NGF production.

Animals↗
PubMed1986

Nerve growth factor gene expression in the developing rat brain.

The regulation of nerve growth factor (NGF) protein and NGF messenger RNA (mRNA) in the developing rat brain has been studied to assess the hypothesis that NGF supports the differentiation of cholinergic neurons in the basal forebrain. In the adult, the major targets of these neurons, the hippocampus and neocortex, contain the highest concentrations of NGF mRNA, but comparatively low ratios of NGF protein to its mRNA. In contrast, a high concentration of NGF protein and a low concentration of NGF mRNA were seen in the basal forebrain, consistent with retrograde transport of NGF protein into this region from the neocortex and hippocampus. In these two target regions NGF and NGF mRNA were barely detectable at birth, their concentrations increased to a peak at day 21, and then NGF mRNA, but not NGF protein, declined threefold by day 35. NGF accumulation in the basal forebrain paralleled that in the target regions and preceded an increase in choline acetyltransferase, suggesting that the differentiation of cholinergic projection neurons is indeed regulated by retrogradely transported NGF. In addition, high ratios of NGF protein to NGF mRNA, comparable to that in the basal forebrain, were seen in the olfactory bulb and cerebellum, suggesting that NGF may be transported into these regions by unidentified neurons.

Animals↗
PubMed1986

Fimbria-fornix lesion increases nerve growth factor content in adult rat septum and hippocampus.

Bilateral complete transection of the fimbria-fornix causes a significant increase in nerve growth factor (NGF) content both in the septum and hippocampus of the adult rat as measured by a sensitive immunoassay 7 days after lesioning. The finding, that elevation of NGF in septum (250%) was much more pronounced than that in the hippocampus (30-50%), cannot be explained by retrograde axonal transport. Degeneration of central cholinergic neurons might be a potential trigger for NGF production in the CNS.

Acetylcholinesterase↗
PubMed1986

Time course of the elevation of nerve growth factor (NGF) content in the hippocampus and septum following lesions of the septohippocampal pathway in rats.

Axotomy of cholinergic neurons in the medial septum-diagonal band and degeneration of their terminals in the hippocampus resulting from fornix-fimbria lesions induce elevation of NGF content in these two brain regions. Postlesion levels of cholinergic neuron-specific ChAT activity in the septum suggest that endogenously produced NGF may, at least partly, promote survival of axotomized cholinergic neurons or induce ChAT activity in undamaged cells or both. These findings thus support the proposed trophic role for NGF in central cholinergic neurons.

Acetylcholinesterase↗
PubMed1986

Nerve growth factor induces mast cell degranulation without changing intracellular calcium levels.

Nerve growth factor (NGF) induces degranulation of rat peritoneal mast cells (RPMC) in a dose-dependent manner, providing direct evidence for its action on non-neuronal tissues. Activation of RPMC by NGF depends on lysophosphatidylserine and extracellular calcium. NGF-mediated RPMC degranulation is not coupled to a transient increase in intracellular free calcium ([Ca2+]i). It is suggested that NGF has a unique mode of action independent of [Ca2+]i and presumably also without involving protein kinase C activation as indicated by the effects of phorbol esters and NGF on antigen-evoked [Ca2+]i rise.

Animals↗
PubMed1986

Cholinergic but not monoaminergic denervation increases nerve growth factor content in the adult rat hippocampus and cerebral cortex.

We have investigated whether degeneration of basal forebrain cholinergic neurons is a potential trigger for increased NGF production in the adult rat brain. Electrolytic lesions of cholinergic neurons in the septum-diagonal band and in the nucleus basalis of Meynert induced a transient increase in NGF in the ventral hippocampus (+70%) and cerebral cortex (+125%), respectively. In contrast, selective aminergic denervation of the forebrain by electrolytic lesion of the medial forebrain bundle, did not increase NGF levels in hippocampus and cerebral cortex. Thus, a cholinergic mechanism appears to regulate NGF production in adult rat basal forebrain.

Animals↗
PubMed1986

Effects of pre- and postnatal administration of antibodies to nerve growth factor on the morphological and biochemical development of the rat adrenal medulla: a reinvestigation.

Whether or not adrenal medullary (chromaffin) cells which respond to nerve growth factor (NGF) both in vitro and in vivo require NGF for their normal development is controversial. Systemic deprivation of endogenous NGF by injection of anti-NGF antibodies into rat fetuses or by transfer of anti-NGF to the offspring of autoimmunized mothers has provided conflicting results. We have reinvestigated the effects of a specific antiserum to NGF on the morphology, catecholamine (CA) and neuropeptide (Met-enkephalin, Met-ENK; substance P, SP) content, and choline acetyltransferase (ChAT) activity of the rat adrenal medulla. Fetuses were injected with anti-NGF antibodies on day 17 of gestation and postnatally at daily intervals for 7 days. The histological appearance of adrenal medullae of anti-NGF injected animals was not altered as compared to controls. Ultrastructurally, no degenerative changes or developmental retardation of chromaffin cells could be detected. However, numbers of chromaffin granules per micron 2 of cytoplasmic area were greater and the mean diameters of the cores of adrenaline storage granules were smaller in antibody-treated than in control animals. CA and SP content, ratios of adrenaline to noradrenaline and ChAT activities were identical in anti-NGF-treated and control animals. Anti-NGF antibodies caused a reduction of adrenal Met-ENK by 40% as compared to controls. Superior cervical ganglia from the same animals were used to document immunosympathectomy induced by the antiserum. They displayed the well-established structural alterations and a marked reduction of the CA content. We conclude that administration of anti-NGF antibodies to embryonic and early postnatal rats induces only subtle changes in the ultramorphology of chromaffin cells without altering the development of normal CA levels. The small, yet significant effects of anti-NGF antibodies on adrenal Met-ENK, however, may suggest a role for endogenous NGF in the regulation of opioid peptide metabolism in developing chromaffin cells.

Adrenal Medulla↗
PubMed1985

Sympathectomy inhibits growth of a murine plasmacytoma tumor.

The effects of 6-hydroxydopamine (6-OHDA), N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) and anti-nerve growth factor (anti-NGF) on the development and growth of a tumor of non-neuronal origin were studied in mice. Murine LPC-1 plasmacytoma cells were grown either subcutaneously (s.c.) as solid tumors in the hindleg or intraperitoneally (i.p.) in ascitic form. Growth of s.c. tumors was monitored by caliper measurements of the hindleg at the site of tumor cell inoculation; growth of ascitic tumors was followed by electrophoretic determination in plasma of the tumor associated protein IgG2a kappa, M component. Adult mice were treated with 6-OHDA or DSP-4 six hours prior to tumor cell implantation; newborn mice were treated with anti-NGF and tumor cells were given 9 weeks later. Both chemical- and immunosympathectomy significantly altered the growth pattern of solid and ascitic tumors (P less than 0.0001). The effect of sympathectomy on the growth of solid tumors was most pronounced during the early phase of tumor growth. The data document that the effect of each drug treatment on tumor growth was not due to direct cytotoxic actions of the agents employed on tumor cells but the result of impairment of sympathetic functions. The findings of this study suggest a role of the sympathetic nervous system in tumor growth.

Animals↗
PubMed1984

Nerve growth factor induces plasma extravasation in rat skin.

The intradermal application of both mouse and bovine nerve growth factor induced dose-dependently increased vascular permeability as indicated by Evans blue extravasation. Plasma extravasation by nerve growth factor was markedly reduced by capsaicin pretreatment or a combination of H1- and H2-histamine antagonists. The finding that biologically inactive nerve growth factor failed to elicit protein leakage indicates that plasma extravasation by nerve growth factor is a characteristic of the biologically active molecule.

Animals↗
PubMed1984

Studies of gangliosides in diverse nerve cell cultures.

Primary nerve cell cultures and tumor cells have been analysed with respect to synthesis of gangliosides. Neither developmental aspects of primary cultures nor nerve growth factor-induced fiber extension in PC12 or ZPH tumor cells gave any evidence of an involvement of gangliosides. Thus, it is concluded that neurite sprouting and ganglioside synthesis may not be interrelated, but that gangliosides might well serve as receptors for trophic factors.

Adrenal Gland Neoplasms↗
PubMed1984

Biochemical and anatomical effects of antibodies against nerve growth factor on developing rat sensory ganglia.

The importance of nerve growth factor (NGF) for the development of sensory ganglia was investigated by injecting rat fetuses (16.50 days of gestation) with a single dose of anti-NGF antiserum. Four months later the treated animals showed a very large decrease in substance P- and somatostatin-like immunoreactivities in dorsal root ganglia and skin with a lesser decrease in trigeminal ganglia. Fluoride-resistant acid phosphatase, substance P-, and somatostatin-like immunoreactivities were greatly decreased in the dorsal horn of the spinal cord. No change in neurotensin- and [Met]enkephalin-like immunoreactivities was observed. The anti-NGF antiserum treatment produced a greater than 90% decrease in the number of unmyelinated dorsal root fibers and a 35% decrease in the total number of myelinated fibers. The loss in myelinated fibers was restricted to small-diameter fibers with no change in large-diameter fibers. No change in taste bud morphology was noted, thereby refuting the proposal that anti-NGF antiserum treatment may represent an animal model for familial dysautonomia. The present results indicate that NGF is a necessary requirement for the normal development of a significant population of prenatal rat dorsal root ganglion cells.

Aging↗
PubMed1983

Nerve growth factor antagonizes the neurotoxic action of capsaicin on primary sensory neurones.

The protein nerve growth factor (NGF) is a naturally occurring trophic substance for sympathetic neurones and for at least those primary sensory neurones containing substance P (refs 4-6). Thus retrogradely transported NGF increased substance P and protein content in corresponding dorsal root ganglia. Moreover, anti-NGF antibodies administered to newborn rats decreased substance P and somatostatin levels in dorsal root ganglia and dorsal spinal cord, suggesting an important role for NGF in the postnatal development of peptidergic sensory neurones. These neurones appear to be selectively affected by the neurotoxin capsaicin (8-methyl-N-vanillyl-6-nonenamide). Treatment of newborn rats with capsaicin led to degeneration of primary sensory neurones containing substance P, somatostatin, vasoactive intestinal polypeptide and cholecystokinin. The mechanism by which capsaicin evokes its neurotoxic effect is unknown. We report here that in newborn rats concomitant administration of NGF partially antagonized the deleterious effect of capsaicin on substance P-containing neurones in dorsal root ganglia as assessed by morphological and biochemical criteria. We conclude that capsaicin destroys the perikarya of primary sensory peptidergic neurones by interfering with the action of NGF, probably by blocking its retrograde axonal transport.

Animals↗