Molybdenum deprivation, purine ingestion and an astrocyte-associated motor neurone syndrome in sheep: assumed clinical effects of inosine

Aust Vet J. 2015 Mar;93(3):79-83. doi: 10.1111/avj.12286.

Abstract

Background: An astrocyte-associated motor neurone syndrome was produced in molybdenum-deprived sheep fed xanthosine. Mo-deprived sheep fed inosine, adenosine or guanosine would be also expected to develop astrocyte-associated motor neurone syndromes, because all these purine nucleosides can act as neuromodulators and all depend on the Mo-associated enzyme xanthine oxidase-dehydrogenase for their catabolism.

Design: To investigate the relationship between inosine ingestion and low Mo concentration, eight sheep were fed lucerne chaff with a Mo value <0.10 ppm and the Mo antagonist, sodium tungstate, for 21 weeks, with inosine (35 mg/kg/day) fed for the last 18 of these weeks. This clinical study was uncontrolled.

Results: An astrocyte-associated motor neurone syndrome was produced in three sheep 18-27 months later. It was characterised by diaphragmatic, laryngeal, lingual and pharyngeal muscle weakness. The diaphragmatic muscle weakness was the most severe and potentially lethal.

Conclusion: These findings suggest that purinergic neuromodulation of respiration, vocalisation and swallowing is different to that of limb movement. The syndrome produced, and assumed to be caused by the treatment given, has not been reported in livestock. A similar syndrome is seen in human motor neurone disease, but not in equine motor neurone disease, and this is consistent with it being an upper, not a lower, motor neurone effect.

Keywords: astrocytes; inosine; molybdenum; neuromodulation; purines; respiration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects*
  • Inosine / toxicity*
  • Molybdenum / deficiency*
  • Motor Neuron Disease / chemically induced
  • Motor Neuron Disease / veterinary*
  • Muscle Weakness / chemically induced
  • Muscle Weakness / veterinary
  • Sheep
  • Sheep Diseases / etiology*
  • Syndrome

Substances

  • Inosine
  • Molybdenum