Transition Metal Distribution in the Brain and Spinal Cord of a Rat Model of Myelin Loss

Transition metal concentrations in the central nervous system (CNS) are implicated in neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Multiple Sclerosis. A common symptom of these diseases is demyelination, which is the degradation of the myelin sheath that encapsulates the neurons in vertebrates. A dysmyelinating rodent model (Long Evans Shaker (LES) rodents) was used to characterize the transition metal concentrations in the central nervous system compared to its age-matched controls, to elucidate the contingency between transition metals and myelination in the pathogenesis of neurodegenerative diseases. The concentrations of manganese (Mn), iron (Fe), copper (Cu), and zinc (Zn) in regions of grey matter and white matter have been compared between Shaker rodents and their agematched Long Evans (LE) controls in the cerebellum and spinal cord, using micro probe Synchrotron Radiation X-ray Fluorescence (µSRXRF). Results and Discussion In the cerebellum, the concentration of all elements were significantly increased in the white matter of the Shaker model, and decreased in the gray matter of the Shaker model in comparison to their age and region matched controls. In the spinal cord samples, concentrations of all metals were higher in white matter and grey matter of Shaker rat spinal cord compared to those in the control rat spinal cord. This study demonstrated that µSRXRF sensitivity is sufficient to discriminate between the elemental distributions of gray and white of the brain sections and spinal cords in the two groups. The observed significant increase of Mn, Fe, Zn and Cu in the white matter of the Shaker animals in the cerebellum and spinal cord compared to controls could be the result of astrocytic glial cells replacing the myelin in the CNS [1]. Unlike other imaging techniques, the fine resolution of µSRXRF enables specific regions of gray matter structures namely, the molecular layer and the granule layer to be identified in the rat CNS, and their transition metal concentrations to be quantified. Conclusions This work will further establish µSRXRF as a powerful analytic technique for compositional studies in brain sections from models of brain disease. If further µSRXRF studies could be carried out, a final atlas could be created to represent the expected levels of transition metals in central nervous system of healthy animals, which is currently missing in literature.