Calcium in Neuronal and Glial Response to Axotomy

Abstract

Neurotrauma assumes an instant or delayed disconnection of axons (axotomy), which affects not only neurons, but surrounding glia as well. Not only mechanically injured glia near the site of disconnection, especially transection, is subjected to the damage, but also glia that is remote from the lesion site. Glial cells, which surround the neuronal body, in turn, support neuron survival, so there is a mutual protection between neuron and glia. Calcium signaling is a central mediator of all post-axotomy events, both in neuron and glia, playing a critical role in their survival/regeneration or death/degeneration. The involvement of calcium in post-axotomy survival of the remote, mechanically intact glia is poorly studied. The purpose of this review is to sum up the calcium-involving mechanisms in responses of neurons and glial cells to axotomy to show their importance and to give some suggestions for future research of remote glia in this context.

Keywords: axotomy; calcium; glia; neurotrauma.

Figure 1

Interactions of neuron, glia, and Ca²⁺ ions in the response of neurons and glia to axotomy. Axotomy-induced processes in remote glial cells and their connection with the fate of the neuron (survival and death), as well as the role of Ca²⁺ ions in them, are relatively poorly studied.

Figure 2

Involvement of Ca²⁺ ions, Ca²⁺ channels, and Ca²⁺-dependent proteins in death or survival of remote glial cells (RGC) in crayfish stretch receptors after axotomy (AT), based on our experimental data. AT induces Ca²⁺ influx into axolemma and the elevation of Ca²⁺ levels in cytosol of neuron and glia ([Ca²⁺]_i), promoting the cessation of neuron firing and glial death. The work of SERCA, pumping Ca²⁺ from cytosol, protects remote glial cell from necrosis and apoptosis. Protein kinase C (PKC) and calmodulin kinase II (CaMKII) are involved in the necrosis of RGC, but PKC decreases their apoptosis, as well as Ca²⁺-dependent potassium channels K(Ca). Extracellular Ca²⁺ ([Ca²⁺]_o), promotes apoptosis, but decreases the necrosis of RGC. Sharp arrowheads: increase effects. Blunt arrowheads: decrease effects. Dashed lines: the effect takes place only after AT. Red: detrimental effects. Blue: protective effects.