The fruit bat as an experimental model of the neuropathy of cobalamin deficiency

The fruit bat provides a unique small mammal model of the neurological changes associated with cobalamin deficiency. Work with this model has shown that methionine moderates the development of the neurological impairment. This action does not appear to be via the methyl donor S-adenosylmethionine, but its role in the provision of formate is not excluded. Furthermore, methylation reactions in the nervous system are not impaired in severe cobalamin deficiency, despite low levels of methionine synthetase activity. The accumulation of physiologically inactive analogues of cobalamin also do not appear to be aetiologically important in the neuropathy. Brain folates are minimally affected by severe cobalamin deficiency, although liver folates decrease significantly. Deranged GABA function in the brain may play a role in the symptomatology of cobalamin deficiency. There is some evidence for the hypothesis that deranged fatty acid metabolism in neural tissue contributes to altered membrane structure and hence function. Changes in the properties of membrane proteins may play a contributory role. The biochemical basis of the neuropathy has still to be fully elucidated.