New Pathogenesis of the Cobalamin-Deficient Neuropathy
Authors
Giuseppe Scalabrino
Institute of General Pathology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milano, I
Daniela Veber
Institute of General Pathology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milano, I
Elena Mutti
Institute of General Pathology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milano, I
Keywords:
Cobalamin deficiency, Subacute combined degeneration, Total gastrectomy
Abstract
Subacute combined degeneration (SCD) is considered the neurological counterpart of pernicious anaemia because it is the paradigmatic neurological manifestation of acquired vitamin B12 (cobalamin (Cbl)) deficiency in adulthood. Hitherto, the theories advanced to explain the pathogenesis of SCD have postulated a causal relationship between SCD lesions and the impairment of either or both of two Cbl-dependent reactions. We have identified a new experimental model, the totally gastrectomised (TGX) rat, to reproduce the key morphological features of the disease, and found new mechanisms responsible for the pathogenesis of SCD. We have demonstrated that the neuropathological lesions in TGX rats are not only due to mere vitamin withdrawal but also to the overproduction of the myelinolytic tumour necrosis factor(TNF)-a, nerve growth factor, the soluble(s) CD40:sCD40 ligand dyad, and the reduced synthesis of the neurotrophic agents, epidermal growth factor and interleukin-6. Cbl replacement treatments normalised all of these abnormalities.
