Hypoxia induces rapid and selective injury to alpha-motor nerve terminals

B. Baxter, M. J. Parsons, T. H. Gillingwater, S. H. Parson

Research output: Contribution to journalMeeting abstractpeer-review

Abstract / Description of output

A growing body of evidence shows that presynaptic nerve terminals throughout the nervous system are vulnerable to a range of traumatic, toxic and disease-related neurodegenerative stimuli. Using a novel ex vivo model, we have recently shown that α-motor nerve terminals in several mouse muscles are highly susceptible to hypoxia-reperfusion injury. Hypoxia for 2 h (< 0.25% O2) followed by reperfusion for 2 h in lumbrical muscles triggered loss of neurofilament 168 kDa (NF) and synaptic vesicle 2 (SV2) protein immunoreactivity in about 83% (n = 28) of presynaptic α-motor nerve terminals. This insult did not appear to affect post-synaptic endplates or muscle fibres. We also established that this loss of α-motor nerve terminal morphology occurs by a mechanism distinct from Wallerian degeneration, as the slow Wallerian degeneration (Wlds) gene did not protect nerve terminals from these pathological changes. We now show that 1A muscle spindle afferents and γ-motor terminals appear to be more resistant to hypoxia-reperfusion injury compared with α-motor nerve terminals. Furthermore, we now demonstrate that significant loss of α-motor nerve terminals in mouse lumbrical muscles occurs in response to hypoxia alone, without reperfusion. A time series analysis shows that loss of NF/SV2 immunoreactivity in α-motor nerve terminals first appears after a 1.5-h hypoxia insult and significant loss appears after 2 h, a 23% (n = 20) and 44% (n = 20) loss, respectively. Collectively, these data suggest that α-motor nerve terminals are highly and selectively vulnerable to hypoxic injury and that pathology is rapidly induced within 1.5 h of hypoxia alone. These findings may have clinical implications for the use of surgical tourniquets and in the aetiology of many neurodegenerative diseases where mechanisms relating to hypoxia and hypoxia-reperfusion injury have been implicated.
Original languageEnglish
Pages (from-to)792-793
Number of pages2
JournalJournal of Anatomy
Volume214
Issue number5
DOIs
Publication statusPublished - May 2009

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Estradiol/metabolism
  • Female
  • Follicle Stimulating Hormone/blood/*physiology
  • Inhibins/metabolism
  • Luteinizing Hormone/blood
  • Osmolar Concentration
  • Ovarian Follicle/*physiology
  • Ovary/metabolism/pathology/transplantation
  • Sheep
  • Time Factors

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