Neurological Disorders and Brain Injury

Neurons and satellite glia mutually support survival of each other, but signaling processes that control their life and death after axotomy (AT) are insufficiently explored. We used a simple model object- axotomized crayfish mechanoreceptor consisting of single sensory neuron surrounded by glial envelope. Control: Undamaged mechanoreceptor that saved connection with abdominal ganglion. Necrosis and apoptosis of glial cells increased at 8 hours after AT when death of neurons was not detected yet. 3-fold increase in [Са²⁺]_o induced glial apoptosis in axotomized but not control samples. Unexpectedly, glial necrosis decreased in 3[Са²⁺]_o, but increased in (1/3)[Са²⁺]_o. Inhibition of endoplasmic reticulum Ca-ATPase (SERCA) by thapsigargin induced glial apoptosis after AT but not in control. Calcium ionophore ionomycin induced glial apoptosis both after AT and in control samples. Fluphenazine, inhibitor of calmodulin did not influence glial apoptosis, but induced glial necrosis. Dantrolene and ochratoxin A that release Ca²⁺ from endoplasmic reticulum stimulated AT-induced glial apoptosis but not necrosis. The blockage of mitochondrial permeability pores with cyclosporine A, which prevented calcium release from mitochondria, reduced cell death. Thus, AT combination with high [Са²⁺]_o or with activation of pathways increased [Са²⁺]_i induced apoptosis of glial cells. Decrease in [Са²⁺]_o, inhibition of SERCA, calmodulin, or Ca²⁺ ionophore promoted glial necrosis. Blockage of mitochondrial permeability pores protected glia from axotomy-induced death. So, axotomy induces necrosis and apoptosis of satellite glial cells and Ca²⁺ is involved in the detrimental effect of AT.