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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., (© 2015 Australian Veterinary Association.)

Background: The occurrence of Tribulus terrestris motor neurone disease (MND) in sheep is linked with grazing Tribulus growing on cultivation paddocks. A previous survey found that the molybdenum (Mo) content of Tribulus growing on uncultivated soils in the Coonabarabran district of New South Wales was 3.03 ppm, but on cultivated soils it was <0.04 ppm. Tribulus contains the purine, xanthosine, which functions as a neuromodulator, and the catabolism of xanthosine is Mo-dependent., Design: To investigate the relationship between xanthosine ingestion and low Mo concentration, eight sheep were fed Mo-deficient lucerne chaff (<0.10 ppm), the Mo antagonist, sodium tungstate, and xanthosine (25 mg/kg/day) over 18 weeks and then returned to pasture., Results: Signs of MND developed in two sheep 30 months later and astrocyte degeneration occurred in all sheep., Conclusion: The findings were similar to those observed in sheep with T. terrestris MND, suggesting that the combination of xanthosine ingestion and Mo deficiency may be the cause of this disorder., (© 2012 The Author. Australian Veterinary Journal © 2012 Australian Veterinary Association.)

Objective: To observe the clinical signs of sheep affected by Tribulus terrestris motor neuron disease, to ascertain their response to striatal dopamine reducing drugs, and to examine their brains and spinal cords for microscopic changes., Procedures: Twenty-eight sheep displaying well developed clinical signs of the disorder were observed. Twenty-two of these and 22 normal sheep were then randomly allocated to three groups and treated with diazepam, chlorpromazine, or xylazine. The time that it took an animal to return to a standing position following drug administration was recorded. The brain and complete spinal cord were removed from each of the other six affected sheep and fixed in formalin. Brains were sectioned throughout at 5 mm intervals and spinal cords at 10 mm intervals. All tissues were paraffin embedded and examined by light microscopy. A few samples were examined by electron microscopy., Results: Clinical signs included postural asymmetry with a right:left body-side dominance within the group of 50:50, unequal flaccid paresis in the pelvic limbs, extensor muscle atrophy and adduction of the weaker pelvic limb, and concurrent abduction of the stronger. Forward motion followed either a fixed left or right hand curved trajectory, the sheep no longer being able to choose which. Twelve animals intermittently displayed rotational behaviour that involved loss of postural balance without locomotor activation. The administration of diazepam, chlorpromazine, or xylazine caused limb paresis and sedation, with affected sheep being slower than normal sheep by factors of 8, 3 and 2 respectively, to return to a standing position. There were scattered areas of mild Wallerian degeneration throughout the spinal cord, and in both the brain and the cord there were small numbers of degenerate astrocytes containing novel cytoplasmic pigment granules., Conclusions: Affected sheep had a dysfunction in the control of directional change and this provides a new insight into the normal mechanism for 'turning' in quadrupeds. Directional change requires a functional asymmetry or lateralisation within the upper motor neuron to accommodate a difference in the rate of forward progression of each body side and, simultaneously, a lateral shift of the centre of gravity. The sensitivity of affected sheep to diazepam is consistent with a pre-existing elevation in GABAergic neuronal inhibition, probably as a result of a reduction in glutamatergic neuronal excitation. The cytoplasmic pigment found in degenerate astrocytes was novel and its presence in the brain nuclei known to contribute to turning behaviour could have aetiological significance. The motor output of the basal ganglia in Tribulus neurotoxicity appeared to be excessively inhibitory to the pelvic limb extensor muscles and was asymmetric, causing fixation of the turning posture but not locomotor activation. An intoxication of specific purine sensitive, glutamate releasing astrocytes, located in nuclei controlling turning, was suspected.