Neurite outgrowth in individual neurons of a neuronal population is differentially regulated by calcium and cyclic AMP

Mattson, M. P.; Taylor-Hunter, A; Kater, Stanley B.

doi:10.1523/jneurosci.08-05-01704.1988

Cited by 155 publications

(76 citation statements)

References 33 publications

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“…Similar findings have also been reported in the murine motoneuron cell line NC SSC19 and in primary mouse (moto)neuron cultures (Smirnova et al, 1998b). Together with the reports that local increases in [C a 2ϩ ] i lead to neurite retraction, whereas agents that lower [C a 2ϩ ] i lead to neurite outgrowth and cell survival (Mattson et al, 1988(Mattson et al, , 1989Mattson, 1993), these observations suggest that increases in [C a 2ϩ ] i may contribute to thrombin-mediated neurite retraction.…”

Section: Discussionsupporting

confidence: 85%

Thrombin Perturbs Neurite Outgrowth and Induces Apoptotic Cell Death in Enriched Chick Spinal Motoneuron Cultures through Caspase Activation

et al. 1998

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Increasing evidence indicates several roles for thrombin-like serine proteases and their cognate inhibitors (serpins) in normal development and/or pathology of the nervous system. In addition to its prominent role in thrombosis and/or hemostasis, thrombin inhibits neurite outgrowth in neuroblastoma and primary neuronal cells in vitro, prevents stellation of glial cells, and induces cell death in glial and neuronal cell cultures. Thrombin is known to act via a cell surface protease-activated receptor (PAR-1), and recent evidence suggests that rodent neurons express PAR-1. Previously, we have shown that the thrombin inhibitor, protease nexin-1, significantly prevents neuronal cell death both in vitro and in vivo. Here we have examined the effects of human ␣-thrombin and the presence and/or activation of PAR-1 on the survival and differentiation of highly enriched cultures of embryonic chick spinal motoneurons. We show that thrombin significantly decreased the mean neurite length, prevented neurite branching, and induced motoneuron death by an apoptosis-like mechanism in a dose-dependent manner. These effects were prevented by cotreatment with hirudin, a specific thrombin inhibitor. Treatment of the cultures with a synthetic thrombin receptor-activating peptide (SFLLRNP) mimicked the deleterious effects of thrombin on motoneurons. Furthermore, cotreatment of the cultures with inhibitors of caspase activities completely prevented the death of motoneurons induced by either thrombin or SFLLRNP. These findings indicate that (1) embryonic avian spinal motoneurons express functional PAR-1 and (2) activation of this receptor induces neuronal cell degeneration and death via stimulation of caspases. Together with previous reports, our results suggest that thrombin, its receptor(s), and endogenous thrombin inhibitors may be important regulators of neuronal cell fate during development, after injury, and in pathology of the nervous system.

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Section: Discussionsupporting

confidence: 85%

Thrombin Perturbs Neurite Outgrowth and Induces Apoptotic Cell Death in Enriched Chick Spinal Motoneuron Cultures through Caspase Activation

et al. 1998

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“…Our data suggest the hypothesis that as early as we have looked, the 5HT-cAMP-I KS cascade is in place and appears mature whereas the 5HT-PKC-I KV cascade does not emerge until much later. A similar temporal dissociation in the development of 5HT activation of PKA-and PKC-dependent pathways has been demonstrated for the development of 5HT responsiveness in the Retzius cell of the leech (26), suggesting that there may be a conserved function for the sequence of expression of PKA-and PKC-mediated pathways in development, perhaps in the regulation of outgrowth and neuronal morphogenesis (27).…”

Section: Discussionsupporting

confidence: 54%

Developmental emergence of different forms of neuromodulation in Aplysia sensory neurons

Marcus

Carew

1998

Proc. Natl. Acad. Sci. U.S.A.

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The capacity for neuromodulation and biophysical plasticity is a defining feature of most mature neuronal cell types. In several cases, modulation at the level of the individual neuron has been causally linked to changes in the functional output of a neuronal circuit and subsequent adaptive changes in the organism's behavioral responses. Understanding how such capacity for neuromodulation develops therefore may provide insights into the mechanisms both of neuronal development and learning and memory. We have examined the development of multiple forms of neuromodulation triggered by a common neurotransmitter, serotonin, in the pleural sensory neurons of Aplysia californica. We have found that multiple signaling cascades within a single neuron develop sequentially, with some being expressed only very late in development. In addition, our data suggest a model in which, within a single neuromodulatory pathway, the elements of the signaling cascade are developmentally expressed in a ''retrograde'' manner with the ionic channel that is modulated appearing early in development, functional elements in the second messenger cascade appearing later, and finally, coupling of the second messenger cascade to the serotonin receptor appearing quite late. These studies provide the characterization of the development of neuromodulation at the level of an identified cell type and offer insights into the potential roles of neuromodulatory processes in development and adult plasticity.

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“…Polyclonal Fabs against N-CAM and Li on PC-12 cells have been shown to reduce levels of inositol phosphates, lower intracellular pH, and increase intracellular Ca2+ (22). Conversely, drugs that alter intracellular protein phosphorylation can influence the outgrowth of neurites (12,13,23). It may also be relevant that cell surface molecules with extracellular homology to N-CAM can have cytoplasmic domains with phosphoprotein phosphatase activity (24).…”

Section: Methodsmentioning

confidence: 99%

Phosphorylation-dependent regulation of axon fasciculation.

Cervello

Lemmon

Landreth³

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Axons often grow along other axons to produce bundles called fascicles, and a number of cell adhesion molecules (CAMs) found on axon surfaces contribute to this process. The surprising observation that Fab fragments against individual CAMs can completely block fascicle formation suggests that the different axon-associated CAMs are functionally linked. The present studies investigate whether such a linkage might reflect intracellular regulatory mechanisms. Results obtained with chicken retinal explants in culture indicate that fasciculation is highly sensitive to cytoplasmic protein phosphorylation by means of a mechanism that does not alter levels of CAM expression. Moreover, the potent effect of individual Fabs on fasciculation disappears with enhanced phosphorylation. These observations suggest that growing axons possess a general regulatory process for the multiple CAMs that participate in fasciculation.Over the past few years a number of cell-cell adhesion molecules (CAMs) have been identified on the surface of axonal processes in the vertebrate embryo (for review, see ref.1). Not surprisingly, most of these molecules appear to contribute to the formation of axon bundles called fascicles. It has been shown that Fab fragments of antibodies specific to each CAM are potent inhibitors ofoverall axon fasciculation in vitro (2-7). This robust inhibition of an adhesion-related phenomenon is consistent with the proposal that these cell-surface molecules act as receptors in the formation of cell-cell bonds. However, the inhibition also represents an unexplained anomaly: if several of these different adhesion receptors are coexpressed on axons, why does addition of Fab against just one receptor almost completely inhibit bundling? The predicted result, which is, in fact, obtained in simple cell aggregation studies (8) and with axon growth on nonneuronal cells (9, 10) is partial inhibition by each Fab and strong inhibition only by a combination of antibodies.There is growing evidence that complex adhesion-related behaviors of growth cones, such as neurite outgrowth and fasciculation (11-13), can be influenced by nerve growth factor or through second-messenger systems. In this study, we have examined three different adhesion molecules involved in fasciculation, neural CAM (N-CAM) (1, 2), G4/L1 (3, 4), and F11 (4), in terms of the possibility that such anomalous Fab effects may be mediated through intracellular events. The results support the idea that cytoplasmic phosphorylation is a major determinant in neurite bundling and also underlies the ability of Fab fragments against one adhesion molecule to alter the overall state of fasciculation. METHODS Materials. Okadaic acid was purchased from Diagnostic Chemicals, Oxford, CT; all other drugs were purchased from Sigma. Rabbit polyclonal antibodies against N-CAM and G4/Li were prepared against immunoaffinity-purified antigens; polyclonal anti-Fli was from F. Rathjen (Center for Molecular Biology, Hamburg, F.R.G.). Fab fragments were prepared by pepsin digestion and ...

show abstract

Neurite outgrowth in individual neurons of a neuronal population is differentially regulated by calcium and cyclic AMP

Cited by 155 publications

References 33 publications

Thrombin Perturbs Neurite Outgrowth and Induces Apoptotic Cell Death in Enriched Chick Spinal Motoneuron Cultures through Caspase Activation

Thrombin Perturbs Neurite Outgrowth and Induces Apoptotic Cell Death in Enriched Chick Spinal Motoneuron Cultures through Caspase Activation

Developmental emergence of different forms of neuromodulation in Aplysia sensory neurons

Phosphorylation-dependent regulation of axon fasciculation.

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