MODEL FOR COBALAMIN DEFICIENCY

Project: Research project

Description

Cobalamin (vitamin B12, Cb1) deficiency can be readily induced in fruit
bats (Rousettus aegyptiacus) which are deprived of a dietary source of the
vitamin in captivity. They develop an illness with neurological
complications, resembling those seen in human pernicious anemia, but
without hematological complications. The features of this potential animal
model for study of human Cb1 deficiency will be further investigated along
the following lines in cb1-deficient and replete bats. Nutritional studies
will be extended to compare the effects of cb1, methionine and choline in
preventing the neurological changes. Biochemical studies will be carried
out to assess whether methylmalonyl CoA mutase or methionine synthetase is
the key enzyme in relation to the role of cb1 in the nervous system. The
origin and fate of organic acids found in urine in cb1 deficiency will be
investigated, and the incorporation of radiolabelled propionate and
methylmalonate into myelin lipids will be measured in brain, spinal cord
and peripheral nerves. The profile of intracellular forms of cb1 will be
analyzed using high performance liquid chromatographpy (hplc). Analysis of
nervous system folates will be carried out by hplc and the effects of
folate on the neuropathy will be tested. The effects of nitrous oxide, a
putative cb1 antagonist, will be compared with the pure nutritional cb1
deficient model. Nerve conduction studies and sensory evoked potentials
will be measured in normal and cb1 deficient animals. Structural studies
and myelin lipid analysis will be carried out on the brains and spinal
cords or bats, including young bats born in captivity. This project seeks
to elucidate the metabolic role of cb1 in nervous system tissue and its
interaction with other nutrients, notably methionine and folate.
StatusFinished
Effective start/end date9/1/833/31/87

Funding

  • National Institutes of Health

Fingerprint

Vitamin B 12
Myelin Sheath
Folic Acid
Methionine
Nervous System
Methylmalonyl-CoA Mutase
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
Vitamin B 12 Deficiency
Lipids
Nerve Tissue
Pernicious Anemia
Neural Conduction
Propionates
Brain
Nitrous Oxide
Choline
Peripheral Nerves
Urine
Food
Acids

ASJC

  • Medicine(all)
  • Neuroscience(all)