Neuropathology of experimental vitamin B ¹² deficiency in monkeys

Abstract

We have produced severe vitamin B12 deficiency in rhesus monkeys by feeding them a defined experimental diet under controlled conditions. Five years after institution of the deficient diet, the morphology and counts of peripheral blood and bone marrow are normal. Gross visual impairment appeared in five of the monkeys between 33 and 45 months after the institution of the vitamin B12 deficient diet. Subsequently, in three of the visually impaired animals, a gradually progressive spastic paralysis of their hind limbs developed. Autopsies of six deficient animals showed degeneration of the peripheral visual pathway in all and of white matter in the spinal cord in four. Degeneration of several cranial nerve roots was found in four monkeys and a mild diffuse degeneration of cerebral white matter in four. The lesions in all affected parts of the central nervous system were bilaterally symmetrical and were indistinguishable from those due to B12 deficiency in the human. No abnormalities were found in one B12 supplemented control animal.

Inherited Selective Intestinal Cobalamin Malabsorption and Cobalamin Deficiency in Dogs

“…Additionally, gastrointestinal mucosal atrophy, lymphoid depletion or hypoplasia, and low IgG concentrations noted in the untreated, affected dogs were changes probably caused or exacerbated by protein-calorie malnutrition. We did not observe neurologic changes in Cbldeficient dogs analogous to subacute combined degeneration of the CNS in Cbl-deficient humans, monkeys, or fruit bats (35)(36)(37). This may have been the result of species differences of Cbldependent metabolism or of insufficient duration of Cbl deficiency in the dogs.…”

Age-related hearing loss, vitamin B-12, and folate in elderly women

“…Auditory dysfunction has been associated with deficiencies of several micronutrients in humans (6)(7)(8)(9) and young growing animals (10)(11)(12)(13)(14). However, we found no studies in humans or experimental animals that specifically examined the role of nutrition in age-related hearing loss.…”

“…Only a few investigators have examined the possible associations between poor vitamin B-12 (8,9,14,(26)(27)(28) or folate (8) status and auditory dysfunction, and little attention has been given to the possible role of these nutrients in age-related hearing loss. Therefore, the objective of this study was to determine whether age-related hearing loss is associated with poor vitamin B-12 status, poor folate status, or both.…”

Inhibition of cobalamin-dependent enzymes by cobalamin analogues in rats.

“…Lengthy periods (up to 3 yr) of dietary deprivation with prevention of copraphagia (2), or inhaled nitrous oxide (N20) have been used in the past to produce the deficient state (3).…”

“…To test the metabolic effects of the administration of cbl analogues to rats, eight experimental male Sprague-Dawley rats (300-400 g size) and eight simultaneous control rats were implanted subcutaneously with model 2002 osmotic minipumps (Alza Corp., Palo Alto, CA) which contained -1 mg OH-cbl analogue in H20 or H20 alone, respectively. The pumps released 2 Ag/h for 14 d (672 ,g total). In one experiment, pumps were replaced at 21 d and the animals were sacrificed after 42 d. Rats were sacrificed with ether, blood was immediately obtained by cardiac puncture, and the livers were immediately frozen in a dry ice acetone bath.…”