Multiple sclerosis (MS) affects the brain and spinal cord. It damages the nerves due to chronic inflammation. The autoimmune reaction of CD4 T lymphocytes against myelin was the prevalent pathogenesis. But new studies propose idiopathic brain damage with autoimmunity as a secondary reaction. This study investigates the role of axon-myelin morphological changes in MS development.
The study uses histological brain specimens and high-resolution imaging on MS patients. It also relies on non-MS or non-neurological controls. The molecular changes in normal-appearing white matter (NAWM) are investigated. This region has normal myelination and no inflammatory activity. The underpinning imbalances in axon-myelin interactions are explored to implicate them as a primary event in MS progress.
The myelin detachment from axons in MS patients showed blister-like swellings. The swelling detection in the control group was substantially less frequent. The MS NAWM swelling presented myelin-associated glycoprotein (MAG) distribution and altered expression of the glutamate receptor. It also presented a lipid biochemical composition of the sheaths. Ranvier node widening, tethering protein expression changes, and sodium channel distribution alterations in nodal regions were also present. In the MS cases, myelin had significant citrullinated protein increase, indicating biochemical modifications leading to amplified immunogenicity.
The impaired, collective myelin-axon interactions can potentially disintegrate the myelin. The subsequent myelin antigen release can provoke an immune attack in MS.