Abstract
Poly(ADP-ribose) polymerase-1 (PARP1) plays a regulatory role in apoptosis, necrosis, and other cellular processes after injury. Recently, we revealed that PARP1 regulates the differential neuronal/astroglial responses to pilocarpine-induced status epilepticus (SE) in the distinct brain regions. In addition, P2X7 receptor (P2X7R), an ATP-gated ion channel, activation accelerates astroglial apoptosis, while it attenuates clasmatodendrosis (lysosome-derived autophagic astroglial death). Therefore, we investigated whether P2X7R regulates regional specific astroglial PARP1 expression/activation in response to SE. In the present study, P2X7R activation exacerbates SE-induced astroglial apoptosis, while P2X7R inhibition attenuates it accompanied by increasing PARP1 activity in the molecular layer of the dentate gyrus following SE. In the CA1 region, however, P2X7R inhibition deteriorates SE-induced clasmatodendrosis via PARP1 activation following SE. Taken together, our findings suggest that P2X7R function may affect SE-induced astroglial death by regulating PARP1 activation/expression in regional-specific manner. Therefore, the selective modulation of P2X7R-mediated PARP1 functions may be a considerable strategy for controls in various types of cell deaths.
Highlights
It has been reported that astroglial death/damage occurs following epilepsy, brain ischemia and Alzheimer’s diseases (Liu et al, 1999; Kang et al, 2006; Olabarria et al, 2010)
P2X7 receptor (P2X7R) does not Affect Neuronal Poly(ADP-ribose) polymerase-1 (PARP1) Expression in Response to status epilepticus (SE) Recently, we have reported that PARP1 activation/expression shows regional- and cellular specific responses to seizure in a hemodynamic-independent manner (Kim et al, 2014)
P2X7R inhibition prevented SE-induced astroglial loss accompanied by preservation of PARP1 expression and PAR synthesis in the molecular layer of the dentate gyrus, where acute astroglial apoptosis is observed 3–7 days after SE (Kim et al, 2010, 2011)
Summary
It has been reported that astroglial death/damage occurs following epilepsy, brain ischemia and Alzheimer’s diseases (Liu et al, 1999; Kang et al, 2006; Olabarria et al, 2010). Astroglial death in the CA1 region shows extensive swelling and vacuolization of cell bodies, and/or disintegrated and beaded processes in the CA1 region (Kim et al, 2008; Kim and Kang, 2011). This irreversible astroglial degeneration is first reported by Alzheimer in 1910, termed ‘‘clasmatodendrosis’’ by Cajal (Penfield, 1928), and is relevant to lysosome-derived autophagy (Ryu et al, 2011a,b).
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