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.