Relation between the rate of stimulation and the quantity of noradrenaline liberated from sympathetic nerve endings in the isolated perfused spleen of the cat.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
H Thoenen
Publications and source records attributed to H Thoenen.
[On the effect of chlorpromazine on postganglionic sympathetic transmission].
Explore the source record for details and available documents.
Animals↗
Dual site of action of phenoxybenzamine in the cat's spleen; blockade of alpha-adrenergic receptors and inhibition of re-uptake of neurally released norepinephrine.
Explore the source record for details and available documents.
Animals↗
Are there differences between the secretion characteristics of NGF and BDNF? Implications for the modulatory role of neurotrophins in activity-dependent neuronal plasticity.
In previous experiments the activity-dependent secretion of nerve growth factor (NGF) from native hippocampal slices and from NGF-cDNA transfected hippocampal neurons showed unusual characteristics [Blochl and Thoenen (1995) Eur J Neurosci 7:1220-1228; (1996) Mol Cell Neurosci 7:173-190]. In both hippocampal slices and cultured hippocampal neurons the activity-dependent secretion proved to be independent of extracellular calcium, but dependent on the release of calcium from intracellular stores. Under different experimental conditions, Goodman et al. [(1996) Mol Cell Neurosci 7:222-238] reported that the high potassium-mediated secretion of brain-derived neurotrophic factor (BDNF) from hippocampal cultures was dependent on extracellular calcium. Mowla et al. [(1997) Proc 27th Annu Meet Soc Neurosci New Orleans 875.10] reported on even further-reaching differences between NGF and BDNF secretion, namely, that in hippocampal neurons and in pituitary cell lines NGF was secreted exclusively according to the constitutive pathway, whereas BDNF was exclusively sorted according to the activity-dependent regulated pathway. In view of the crucial importance of such potential differences between the processing, sorting, and secretory mechanisms of different neurotrophins for their modulatory roles in activity-dependent neuronal plasticity, a thorough analysis under comparable experimental conditions was mandatory. We demonstrate that in native hippocampal slices and adenoviral-transduced hippocampal neurons there are no differences between NGF and BDNF with respect to the subcellular distribution and mechanism of secretion; that the activity-dependent secretion of both NGF and BDNF is dependent on intact intracellular calcium stores; and that the differences between our own observations and those of Goodman et al. (ibid.) regarding the dependence on extracellular calcium do not reflect differences between NGF and BDNF sorting and secretion, but reflect the differing experimental conditions used.
Animals↗
Different factors from the central nervous system and periphery regulate the survival of sensory neurones.
Work on nerve growth factor has established that the survival of developing vertebrate neurones depends on the supply of a neurotrophic factor from their target field. The discovery of several new neurotrophic factors has raised the possibility that neurones which innervate multiple target fields require several different neurotrophic factors for survival. Here we show that two distinct neurotrophic factors, one in the central nervous system (CNS) and the other in skeletal muscle, promote the survival of proprioceptive neurones in culture. At saturating concentrations, either factor alone supported most neurones and there was no additional survival in the presence of both factors, but at subsaturating concentrations the combined effect was additive. The neurotrophic activity of each factor was greatest during the period of natural neuronal death. Our results demonstrate that each cultured proprioceptive neurone responds to two distinct neurotrophic factors present in its respective central and peripheral target fields, and suggest that these factors cooperate in regulating survival during development.
Animals↗
Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor.
We show that nerve growth factor (NGF) synthesis in developing skin begins with sensory innervation and that sensory neurons do not express NGF receptors until their fibres reach their cutaneous targets. Both cutaneous epithelium and mesenchyme synthesize NGF, the concentration of messenger RNA for NGF being higher in the more densely innervated epithelium.
Animals↗
Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve.
The Schwann cells and fibroblast-like cells of the intact sciatic nerve of adult rats synthesize very little nerve growth factor (NGF). After lesion, however, there is a dramatic increase in the amounts of both NGF-mRNA and NGF protein synthesized by the sciatic non-neuronal cells. This local increase in NGF synthesis partially replaces the interrupted NGF supply from the periphery to the NGF-responsive sensory and sympathetic neurons, whose axons run within the sciatic nerve. Macrophages, known to invade the site of nerve lesion during wallerian degeneration, are important in the regulation of NGF synthesis. Here we demonstrate that the effect of macrophages on NGF-mRNA levels in cultured explants of sciatic nerve can be mimicked by conditioned media of activated macrophages, and that interleukin-1 is the responsible agent.
Animals↗
Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor.
Ciliary neurotrophic factor (CNTF) was originally characterized as a survival factor for chick ciliary neurons in vitro. More recently, it was shown to promote the survival of a variety of other neuronal cell types and to affect the differentiation of E7 chick sympathetic neurons by inhibiting their proliferation and by inducing the expression of vasoactive intestinal peptide immunoreactivity (VIP-IR). In cultures of dissociated sympathetic neurons from newborn rats, CNTF induces cholinergic differentiation as shown by increased levels of choline acetyltransferase (ChAT). This increase is paralleled by a reduction of tyrosine hydroxylase (TH) activity. Moreover, CNTF promotes the differentiation of bipotential 02A progenitor cells to type-2-astrocytes in vitro. To help establish which, if any, of these functions CNTF exerts in vivo, it is necessary to determine its primary structure, cellular expression, developmental regulation and localization. The complementary DNA-deduced amino-acid sequence and subsequent expression of cDNA clones covering the entire coding region in HeLa-cells indicate that CNTF is a cytosolic protein. This, together with its regional distribution and its developmental expression, show that CNTF is not a target-derived neurotrophic factor. CNTF thus seems to exhibit neurotrophic and differentiation properties only after becoming available either by cellular lesion or by an unknown release mechanism.
Amino Acid Sequence↗
Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section.
Motoneurons innervating the skeletal musculature were among the first neurons shown to require the presence of their target cells to develop appropriately. But the characterization of molecules allowing motoneuron survival has been difficult. Ciliary neurotrophic factor prevents the death of motoneurons, but its gene is not expressed during development. Although the presence of a neurotrophin receptor on developing motoneurons has suggested a role for neurotrophins, none could be shown to promote motoneuron survival in vitro. We report here that brain-derived neurotrophic factor can prevent the death of axotomized motoneurons in newborn rats, suggesting a role for this neurotrophin for motoneuron survival in vivo.
Animals↗