Status Epilepticus in the Immature Rodent Brain Alters the Dynamics of Autophagy
Alexander Philipp Benz, Jerome Niquet, Claude Guy Wasterlain and Abdelhaq Rami
Affiliation: Anatomie III, Universitatsklinikum, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
There is considerable interest in defining the molecular pathways involved in seizure-induced neuronal death.
Necrotic, apoptotic and anti-apoptotic signalling pathways are activated after status epilepticus (SE). Analyses of
apoptosis and necrosis have been merely reported, however conditions of autophagic cell death with hallmarks of type 2
programmed cell death-morphology are relatively few. Autophagy is a highly regulated cellular mechanism for the bulk
degradation of cytoplasmic contents which is involved in a variety of physiological and pathological conditions associated
with neurological diseases. Our goal was to examine whether autophagy is implicated in the cell death machinery after
SE. For this purpose, we used lithium-pilocarpine model of SE in 14-day-old rats and examined the dynamics in the
expression of autophagic markers in the hippocampus in controls and in animals subjected to SE at 6, 24, and 48h after the
insult. Protein levels of central components of the autophagic machinery were dramatically affected by SE with, however,
altered dynamics, compared to controls. Levels of LC3, phospho-mTOR/mTOR, BAG3 and Hsp70 were significantly
increased, whereas Beclin 1 levels remained unchanged after SE. The dynamics in the expression of Atg3, Atg5, Atg7,
Atg14 and LAMP1 were slightly altered. The amount of SQSTM1/p62 underwent a dramatic and highly significant
breakdown 48 h after the induction of SE. These results demonstrate for the first time that SE in the immature brain
results in significant alterations of autophagy dynamics. There is a growing interest in the role of autophagy in
neurodegeneration, and an emerging consensus that autophagy represents a double-edged sword, acting either as a
prosurvival mechanism, or as part of a cell death pathway.
Keywords: Apoptosis, autophagy, hippocampus, immature brain, neurodegeneration, rat, status epilepticus.
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