Neuron-specific and state-specific differences in calcium homeostasis regulate the generation and degeneration of neuronal architecture

Mills, Linda R.; Kater, Stanley B.

doi:10.1016/0896-6273(90)90451-k

Cited by 94 publications

(58 citation statements)

References 43 publications

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“…Although large changes in calcium clearly can disrupt the stability of growth cone actin and cause DRG growth cones to collapse (Lankford and Letoumeau, 1989; present results), smaller changes in calcium levels appear to be tolerated well by these growth cones. Calcium homeostatic mechanisms have been described in the growth cones and cell bodies of Helisoma neurons (Mills and Kater, 1990). The calcium homeostatic mechanisms operating in these DRG growth cones also seem to be very potent.…”

Section: Resultsmentioning

confidence: 99%

Intracellular calcium levels do not change during contact-mediated collapse of chick DRG growth cone structure

1991

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When the growth cone of a chick dorsal root ganglion (DRG) neurite contacts the neurite of a chick retinal ganglion cell in vitro, the growth cone typically responds by withdrawing its lamellipodia and filopodia and collapsing. We have used the fluorescent calcium indicator dye fura-2 and digital imaging microscopy to measure calcium levels within DRG growth cones and to determine whether changes in calcium levels are responsible for the collapse of growth cone morphology when a DRG growth cone contacts a retinal ganglion cell neurite. Calcium levels within DRG growth cones were stable during neurite outgrowth. Calcium was typically distributed homogeneously throughout the growth cone, though occasionally gradients of free calcium were present. When calcium gradients were observed, calcium levels appeared higher in the active veil regions than in the central core region. Calcium levels in DRG growth cones appeared to remain stable during the period of contact-mediated growth cone collapse. Low concentrations of the calcium ionophore ionomycin increased calcium levels two- to threefold without having any observable morphological effects on DRG growth cones. Likewise, depolarization with 15 mM KCl caused a transient two- to threefold increase in calcium levels without having any observable morphological effect. These results suggest that changes in calcium levels are not responsible for contact-mediated collapse of growth cone structure. A growth cone collapsing activity has been solubilized from embryonic chick brain (Raper and Kapfhammer, 1990). Application of this material to cultures of DRG neurons caused growth cones to collapse but had no effect on calcium levels within the growth cones. The crude growth cone collapsing activity was not blocked by the presence of cobalt, nickel, lanthanum, nifedipine, or reduced- calcium medium, suggesting that transmembrane calcium fluxes were not required for growth cone collapse. These results suggest that the morphological changes associated with the collapse of growth cone structure can be independent of changes in growth cone calcium levels, and that second messengers other than calcium are likely to be involved in the regulation of many growth cone behaviors.

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Section: Resultsmentioning

confidence: 99%

Intracellular calcium levels do not change during contact-mediated collapse of chick DRG growth cone structure

1991

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“…Interestingly, both increases [Cohan et al, 1987;Connor, 1986;Lankford and Letourneau, 1989;Mattson and Kater, 1987;Mattson et al, 1988d,e;McCobb et al, 1988;Mills and Kater, 1990;Silver et al, 19891 and decreases [Anglister et al, 1982;Connor, 1986;Goldberg, 1988;Lankford and Letourneau, 1989;Mattson and Kater, 1987;Saurez-Isla et al, 19871 in growth cone calcium levels have been associated with inhibition of neurite outgrowth, often in the same neuronal types. These observations have given rise to the hypothesis that there may be a relatively narrow range of growth cone calcium concentrations which are permissive for neurite outgrowth, with both higher and lower calcium levels being incompatible with one or more processes necessary for neurite extension Mattson and Kater, 19871.…”

Section: Introductionmentioning

confidence: 95%

Roles of actin filaments and three second‐messenger systems in short‐term regulation of chick dorsal root ganglion neurite outgrowth

Lankford

Letourneau

1991

Cell Motil. Cytoskeleton

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In a previous study (J. Cell Biol. 109: 1229-1243, 1989), we reported that conditions which increased growth cone calcium levels and induced neurite retraction in cultured chick DRG neurons also resulted in an apparent loss of actin filaments in the growth cone periphery. We further showed that the actin-stabilizing drug phalloidin could block or reverse calcium-ionophore-induced neurite retraction, indicating that the behavioral changes were mediated, at least in part, by changes in actin filament stability. In this study, we have further characterized the calcium sensitivity of growth cone behavior to identify which features of calcium-induced behavioral effects can be attributed to effects on actin filaments alone, and to assess whether two other second-messenger systems, cAMP and protein kinase C, might influence neurite outgrowth by altering calcium levels or actin stability. The results indicated that growth cone behavior was highly sensitive to small changes in calcium concentrations. Neurite outgrowth was only observed in calcium-permeabilized cells when extracellular calcium concentrations were between 200 and 300 nM, and changes as small as 50 nM commonly produced detectable changes in behavior. Furthermore, low doses of cytochalasins mimicked all of the grossly observable features of growth cone responses to elevation of intracellular calcium, including the apparent preferential destruction of lamellipodial actin filaments and sparing of filopodial actin, suggesting that the behavioral effects of calcium elevation could be explained by loss of actin filaments alone. The effects of cAMP elevation and protein kinase C activation on growth cone behavior, ultrastructure, and fura2-AM-measured calcium levels indicated that the effects of cAMP manipulations could be partially explained by a cAMP-induced lowering of growth cone calcium levels and concomitant increased stabilization of actin filaments, but protein kinase C appeared to act through an independent mechanism.

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“…72 Glucocorticoids may mediate these effects by enhancing calcium currents in the hippocampus, 73 since calcium ions have a key role in destructive as well as plastic processes in hippocampal neurons. [74][75][76] The persistent release of the excitatory amino acid glutamate in the hippocampus after stress in aged rats may also contribute to age-related neuronal damage 27 and may potentiate atrophy and possibly even neuronal loss.…”

Section: The Brainmentioning

confidence: 99%

Protective and Damaging Effects of Stress Mediators

1998

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VER 60 years ago, Selye 1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators.This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load. 2 Allostasis -the ability to achieve stability through change 3 -is critical to survival. Through allostasis, the autonomic nervous system, the hypothalamic-pituitary-adrenal (HPA) axis, and the cardiovascular, metabolic, and immune systems protect the body by responding to internal and external stress. The price of this accommodation to stress can be allostatic load, 2 which is the wear and tear that results from chronic overactivity or underactivity of allostatic systems.

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Neuron-specific and state-specific differences in calcium homeostasis regulate the generation and degeneration of neuronal architecture

Cited by 94 publications

References 43 publications

Intracellular calcium levels do not change during contact-mediated collapse of chick DRG growth cone structure

Intracellular calcium levels do not change during contact-mediated collapse of chick DRG growth cone structure

Roles of actin filaments and three second‐messenger systems in short‐term regulation of chick dorsal root ganglion neurite outgrowth

Protective and Damaging Effects of Stress Mediators

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