Pharmacological induction of Heat Shock Protein 70 by celastrol protects motoneurons from excitotoxicity in rat spinal cord in vitro

Autor: Andrea Nistri, Jaspreet Kaur, Ivana Tomljanović, Antonela Petrović, Miranda Mladinic
Rok vydání: 2018
Předmět:
Male
Cell Survival
Excitotoxicity
Kainate receptor
medicine.disease_cause
Neuroprotection
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line
Tumor

Heat shock protein
medicine
Animals
Humans
HSP70 Heat-Shock Proteins
Rats
Wistar

heat shock proteins
neonatal rat spinal cord preparation in vitro
nuclear apoptosis-inducing factor
spinal cord injury
spinal motoneurons
Spinal cord injury
Spinal Cord Injuries
030304 developmental biology
Motor Neurons
0303 health sciences
Kainic Acid
business.industry
General Neuroscience
medicine.disease
Spinal cord
Triterpenes
Hsp70
Neuroprotective Agents
medicine.anatomical_structure
Animals
Newborn

Spinal Cord
chemistry
Celastrol
Female
Pentacyclic Triterpenes
business
Neuroscience
Locomotion
030217 neurology & neurosurgery
Zdroj: European Journal of Neuroscience. 49:215-231
ISSN: 0953-816X
DOI: 10.1111/ejn.14218
Popis: The secondary phase of spinal cord injury arising after the primary lesion largely extends the damage severity with delayed negative consequences for sensory‐motor pathways. It is, therefore, important to find out if enhancing intrinsic mechanisms of neuroprotection can spare motoneurons that are very vulnerable cells. This issue was investigated with an in vitro model of rat spinal cord excitotoxicity monitored for up to 24 hr after the primary injury evoked by kainate. This study sought to pharmacologically boost the expression of heat shock proteins (HSP) to protect spinal motoneurons using celastrol to investigate if the rat spinal cord can upregulate HSP as neuroprotective mechanism. Despite its narrow range of drug safety in vitro, celastrol was not toxic to the rat spinal cord at 0.75 μM concentration and enhanced the expression of HSP70 by motoneurons. When celastrol was applied either before or after kainate, the number of dead motoneurons was significantly decreased and the nuclear localization of the cell death biomarker AIF strongly inhibited. Nevertheless, electrophysiological recording showed that protection of lumbar motor networks by celastrol was rather limited as reflex activity was impaired and fictive locomotion largely depressed, suggesting that functional deficit persisted, though the networks could express slow rhythmic oscillations. While our data do not exclude further recovery at later times beyond the experimental observations, the present results indicate that the upregulated expression of HSP in the aftermath of acute injury may be an interesting avenue for early protection of spinal motoneurons.
Databáze: OpenAIRE