ABSTRACT
In patients with Charcot-Marie-Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss during adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit a developmental defect that includes reduced transcription of genes required for myelin lipid biosynthesis. Consequently, lipid incorporation into myelin is reduced, leading to an overall distorted stoichiometry of myelin proteins and lipids with ultrastructural changes of the myelin sheath. Substitution of phosphatidylcholine and phosphatidylethanolamine in the diet is sufficient to overcome the myelination deficit of affected Schwann cells in vivo. This treatment rescues the number of myelinated axons in the peripheral nerves of the CMT rats and leads to a marked amelioration of neuropathic symptoms. We propose that lipid supplementation is an easily translatable potential therapeutic approach in CMT1A and possibly other dysmyelinating neuropathies.
Subject(s)
Charcot-Marie-Tooth Disease/therapy , Lipid Metabolism , Myelin Sheath/metabolism , Animals , Axons/metabolism , Axons/ultrastructure , Dietary Fats/pharmacology , Lipid Metabolism/drug effects , Lipids/biosynthesis , Myelin Sheath/ultrastructure , Phospholipids/metabolism , Rats, Transgenic , Schwann Cells/drug effects , Schwann Cells/metabolism , Schwann Cells/pathologyABSTRACT
A questionnaire was administered to the nursing staff of a large teaching hospital to determine: 1) sources of stress in caring for AIDS patients; 2) perceived sources of stress in being an AIDS patient; and 3) attitudes towards "deserving" various illnesses. Principal components analyses revealed a number of factors related to increased stress, including: general concerns about the care of these patients; specific concerns in crises situations; and concerns regarding the personal/social implications of caring for these individuals. These factors were not related to either prior experience taking care of AIDS patients, or nursing specialty. In addition, persons with AIDS were viewed as "deserving" their illness in much the same way as noncompliant diabetic or renal patients. Potential implications of these findings and suggestions for future research directed towards mitigating these occupational stressors are given.
