New insights into the pathophysiology of cobalamin deficiency

Trends Mol Med. 2006 Jun;12(6):247-54. doi: 10.1016/j.molmed.2006.04.008. Epub 2006 May 11.

Abstract

Cobalamin-deficient (Cbl-D) central neuropathy in the rat is associated with a locally increased expression of neurotoxic tumour necrosis factor-alpha (TNF-alpha) and a locally decreased expression of neurotrophic epidermal growth factor (EGF). These recent findings suggest that cobalamin oppositely regulates the expression of TNF-alpha and EGF, and raise the possibility that these effects might be independent of its coenzyme function. Furthermore, adult Cbl-D patients have high levels of TNF-alpha and low levels of EGF in the serum and cerebrospinal fluid. Serum levels of TNF-alpha and EGF of cobalamin-treated patients normalize concomitantly with haematological disease remission. These observations suggest that cobalamin deficiency induces an imbalance in TNF-alpha and EGF levels in biological fluids that might have a role in the pathogenesis of the damage caused by pernicious anaemia.

MeSH terms

  • Anemia, Pernicious / blood
  • Anemia, Pernicious / cerebrospinal fluid
  • Anemia, Pernicious / drug therapy
  • Anemia, Pernicious / metabolism*
  • Animals
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism*
  • Disease Models, Animal
  • Epidermal Growth Factor / blood
  • Epidermal Growth Factor / cerebrospinal fluid
  • Epidermal Growth Factor / metabolism
  • Gastrectomy
  • Humans
  • Nerve Degeneration / blood
  • Nerve Degeneration / cerebrospinal fluid
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / metabolism*
  • Nerve Growth Factor / blood
  • Nerve Growth Factor / cerebrospinal fluid
  • Nerve Growth Factor / metabolism
  • Rats
  • Tumor Necrosis Factor-alpha / cerebrospinal fluid
  • Tumor Necrosis Factor-alpha / metabolism
  • Vitamin B 12 / pharmacology
  • Vitamin B 12 / therapeutic use
  • Vitamin B 12 Deficiency / blood
  • Vitamin B 12 Deficiency / cerebrospinal fluid
  • Vitamin B 12 Deficiency / drug therapy
  • Vitamin B 12 Deficiency / metabolism*

Substances

  • Tumor Necrosis Factor-alpha
  • Epidermal Growth Factor
  • Nerve Growth Factor
  • Vitamin B 12