Naslov
Ischemia-like conditions In vitro damage rat spinal cord via complex cell death mechanisms

Autori
Bianchetti, Elena ; Mladinic, Miranda ; Nistri, Andrea

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Book of Abstracts Neuroscience 2013, San Diego, CA / - , 2013

Skup
Annual Meeting Of The Society For Neuroscience 2013

Mjesto i datum
San Diego (CA), Sjedinjene Američke Države, 09.11.2013. - 13.11.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
SPINAL CORD INJURY, ISCHEMIA, CELL DEATH

Sažetak
New spinal cord injury (SCI) cases are frequently due to non-traumatic causes, including vascular disorders. To develop mechanism-based neuroprotective strategies for acute SCI requires full understanding of the early pathophysiological changes to prevent disability and paralysis. The immediate damage spreads from the initial site through excitotoxicity and metabolic dysfunction (ischemia, free radicals and neuroinflammation) to surrounding tissue (secondary damage). The aim of our study was identifying molecular and cellular mechanisms underlying this process and triggered by a pathological medium (PM) mimicking ischemia in the neonatal rat spinal cord in vitro. We previously showed that extracellular Mg2+ (1 mM) worsened PM-induced damage and inhibited locomotor function. The current study sought to identify the cells affected by PM with Mg2+, and the associated molecular death pathways. Our focus was on the spinal lumbar region which contains the locomotor networks for the hindlimbs. The present study indicated that 1 h PM+Mg2+ application induced delayed pyknosis chiefly in the spinal white matter via overactivation of poly (ADP-ribose) polymerase 1 (PARP1), suggesting cell death mediated by the process of parthanatos that was largely suppressed by pharmacological block of PARP-1, and also via caspase 3-dependent apoptosis. Grey matter damage was less intense and concentrated in dorsal horn neurons and motoneurons that became immunoreactive for the mitochondrial apoptosis- inducing factor (the intracellular effector of parthanatos) translocated into the nucleus to induce chromatin condensation and DNA fragmentation. Immunoreactivity to TRPM ion channels believed to be involved in ischemic brain damage was also investigated. TRPM2 channel expression was enhanced 24 h later in dorsal horn and motoneurons, while TRPM7 channel expression concomitantly decreased. Conversely, TRPM7 expression grew earlier (3 h) in white matter cells, while TRPM2 remained undetectable. Our results show that extracellular Mg2+ amplified the consequences of dysmetabolic SCI to comprise not only white matter parthanatos and apoptosis, but also motoneuronal degeneration via PARP1-dependent pathways with distinct changes in their TRPM expression. Supported by a grant from FVG regional government.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

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