Changes in white matter ultrastructure in aged mice corpora callosa

Document Type : Original Research

Authors
1 Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
2 Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Abstract
Aging of can lead to significant cognitive and neurobehavioral deficits. In addition, aging leads to more susceptibility to neurological disorders, such as stroke, traumatic brain injury, and neurodegeneration. Accordingly, white matter (WM) changes associated with aging may be a factor in the functional impairment seen in the elderly. In this study, we initially determined whether the corpus callosum (CC) of old mice exhibited signs of cellular aging compared to young mice. To investigate cellular aging indices we examined SA-β-galactosidase and relative telomere length as markers of aging in the CC. Following this, we measured the myelination index through the g-ratio calculation. Our study demonstrated an increased g-ratio and axon diameter in aged mice. We also analyzed ultrastructural changes of myelinated axons and mitochondria in the CC of aged mice. The CC underwent substantial ultrastructural variation following the aging. These changes included myelination breakdown, the formation of myelin balloons, loss of the compact structure of myelin, and increased intramembrane density. we also investigated the impact of aging on mitochondria ultrastructure. We observed the presence of dark matrices and interconnected crista in a subgroup of the mitochondria in the CC. Such alterations are indicative of the deterioration in the integrity of WM with age. These findings are crucial as they provide insights into how aging affects the structural and functional aspects of WM, particularly in the CC. Understanding these changes is essential for developing strategies to mitigate age-related cognitive decline and to address the heightened susceptibility of aged WM to neurological disorders.

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