Astrocytes mediate neuroprotection in a model of hyperactivation, modulating protease calpain activity in neurons

CRAGNOLINI, ANDREA BEATRIZ; VICTOR DANELON; DANIEL MASCÓ

Ciudad Autónoma de Buenos Aires

Congreso; FALAN, Federation of Latin American and Caribbean Neuroscience Meeting; 2016

Federation of Latin American and Caribbean Neuroscience

Epilepsy is a common disease of the central nervous system, characterized by recurrent seizures. Several strategies have been proposed to protect neurons once the pathology has occurred. One of them is the Preconditioning stimulus (PC) an intrinsic phenomenon that protects neurons from subsequent seizure injuries. The molecular mechanisms underlying this neuroprotection have been studied on neurons, without taking astrocyte role account. To determine if astrocytes have a role in this phenomenon we used an in vitro model of Status Epilepticus (SE). In a coculture system, SE alone induced 40% neuronal death 24 hr after completion of SE. If a PC was applied 24h before the SE stimulus, we observed a complete neuronal protection. To study the mechanisms underlying this neuroprotection, we focused on Calpain a family of Ca2+-dependent proteases. It has been demonstrated that a PC when astrocytes are present can modulate neuron calcium response. We hypothesize that a PC modulate neuron calpain activity only when astrocytes are present. In pure hippocampal neuron culture a PC could not modulated calpain activity. When astrocytes were present, the PC was able to modulated calpain activity. Indeed, the inhibition of reactive astrocytes with Fluorocitrate prevented the PC neuroprotection and calpain modulation. These results show that a PC could protect neurons from seizure injury only when astrocytes are present.