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Role of HSP70 in motoneuron survival after excitotoxic stress in a rat spinal cord injury model in vitro
Author(s) -
Shabbir Ayisha,
Bianchetti Elena,
Cargonja Renato,
Petrovic Antonela,
Mladinic Miranda,
Pilipović Kristina,
Nistri Andrea
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13108
Subject(s) - excitotoxicity , neuroprotection , neuroscience , kainate receptor , spinal cord , neurotoxicity , hsp70 , biology , glutamate receptor , medicine , programmed cell death , apoptosis , heat shock protein , ampa receptor , toxicity , biochemistry , receptor , gene
The outcome for gait recovery from paralysis due to spinal lesion remains uncertain even when damage is limited. One critical factor is the survival of motoneurons, which are very vulnerable cells. To clarify the early pathophysiological mechanisms of spinal damage, an in vitro injury model of the rat spinal cord caused by moderate excitotoxicity was used. With this preparation we investigated whether motoneuron survival was dependent on the expression of the neuroprotective protein HSP 70. In the present study excitotoxicity evoked by kainate induced delayed (24 h) loss (35%) of motoneurons, which became pyknotic with translocation of the cell death biomarker apoptosis‐inducing factor ( AIF ) to the nucleus. This process was concomitant with suppression of locomotor network electrical activity. Surviving cells showed strong expression of HSP 70 without nuclear AIF . The HSP 70 inhibitor VER 155008 per se induced neurotoxicity similar to that of kainate, while the HSP 90 inhibitor geldanamycin did not damage spinal tissue. Electrophysiological recording following kainate or VER 155008 indicated depression of motoneuron field potentials, with decreased excitability and impaired synaptic transmission. When these two drugs were applied together, more intense neurotoxicity emerged. Our data indicate that HSP 70 was one important contributor to motoneuron survival and suggest that enhancing HSP 70 activity is a potential future strategy for neuroprotecting these cells.