title: Mitochondrial involvement in sensory neuronal cell death and survival.
abstract: Peripheral nerve injuries (PNI) are continuing to be an ever-growing socio-economic burden affecting mainly the young working population and the current clinical treatments to PNI provide a poor clinical outcome involving significant loss of sensation. Thus, our understanding of the underlying factors responsible for the extensive loss of the sensory cutaneous subpopulation in the dorsal root ganglia (DRG) that occurs following injury needs to be improved. The current investigations focus in identifying visual cues of mitochondria-related apoptotic events in the various subpopulations of sensory cutaneous neurons. Sensory neuronal subpopulations were identified using FastBlue retrograde labelling following axotomy. Specialised fluorogenic probes, MitoTracker Red and MitoTracker Orange, were employed to visualise the dynamic changes of the mitochondrial population of neurons. The results reveal a fragmented mitochondrial network in sural neurons following apoptosis, whereas a fused elongated mitochondrial population is present in sensory proprioceptive muscle neurons following tibial axotomy. We also demonstrate the neuroprotective properties of NAC and ALCAR therapy in vitro. The dynamic mitochondrial network breaks down following oxidative exposure to hydrogen peroxide (H(2)O(2)), but reinitiates fusion after NAC and ALCAR therapy. In conclusion, this study provides both qualitative and quantitative evidence of the susceptibility of sensory cutaneous sub-population in apoptosis and of the neuroprotective effects of NAC and ALCAR treatment on H(2)O(2)-challenged neurons.
authors.affiliation: Blond McIndoe Laboratories, University of Manchester, 3.106 Stopford Building, Oxford Road, Manchester M13 9PT, UK. pavlos.englezou@postgrad.man.ac.uk
authors.forename: Pavlos C
authors.initials: PC
authors.lastname: Englezou
authors.forename: Mauro Degli
authors.initials: MD
authors.lastname: Esposti
authors.forename: Mikael
authors.initials: M
authors.lastname: Wiberg
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Reid
authors.forename: Giorgio
authors.initials: G
authors.lastname: Terenghi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D006861:Hydrogen Peroxide