Mitochondrial involvement in sensory neuronal cell death and survival.

Pavlos C Englezou, Mauro Degli Esposti, Mikael Wiberg, Adam J Reid, Giorgio Terenghi

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)357-367
    Number of pages10
    JournalExperimental brain research
    Volume221
    Issue number4
    DOIs
    Publication statusPublished - Sept 2012

    Keywords

    • Acetyl-Lcarnitine (ALCAR)
    • Dorsal root ganglion (DRG)
    • Mitochondria
    • Mitotracker Red
    • N-acetyl cysteine (NAC)
    • Peripheral nerve injury (PNI)

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