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Peripheral nerve comprises a crucial component of the distributed motor/sensory system. However, there is a paucity of data on peripheral ne… (voir plus)rve morphology derived from large numbers of older adults. This study aimed to quantify the morphometric characteristics of myelinated nerve fibres of the tibial nerve obtained from deceased community-dwelling older adults and examine their association with age. The tibial nerves were obtained from consecutive autopsies of older adults without a history of diabetes who were participants of the Rush Memory and Aging Project, an ongoing longitudinal clinical-autopsy study. A nerve fascicle, obtained from a fixed popliteal segment of the tibial nerve, was separated from the blood vessels and adipose tissue for postmortem examination under an optical microscope. Morphometric characteristics of the myelinated nerve fibres were automatically segmented and quantified using our open-source software AxonDeepSeg. The participants (N = 140) had a mean age of 92.0 years (SD = 5.4) at death, and 72.1% (N = 101) were women. We examined 754 247 myelinated nerve fibres, with an average 5387 (SD = 3436) nerve fibres per participant. The average diameter of myelinated nerve fibres was 4.9 µm (SD = 3.1), axon diameter was 2.0 µm (SD = 1.4), myelin thickness was 1.4 µm (SD = 0.96) and the g-ratio (ratio of axon diameter to myelinated nerve fibre diameter) was 0.45 (SD = 0.17). The relationship between axon diameter and myelin thickness was nonlinear. Myelin was thicker in larger axons up to a diameter of 8 µm, beyond which myelin thickness plateaued. Older age at death was associated with smaller myelinated nerve fibres, smaller axons and thinner myelin. However, age at death was not correlated with myelinated nerve fibre density and was not associated with the average of g-ratio. The association between older age and smaller myelinated nerve fibres was largely attributable to a lower percentage of myelinated nerve fibres >8 µm. We conclude that the smaller tibial myelinated nerve fibres observed in older adults may reflect axonal atrophy rather than degeneration and regeneration of the myelinated nerve fibres. Further research is needed to investigate the pathologies and molecular mechanisms underlying these age-related morphometric changes and their clinical implications in older adults.
Myelin Basic Protein (MBP) is essential for both elaboration and maintenance of CNS myelin, and its reduced accumulation results in hypomyel… (voir plus)ination. How different Mbp mRNA levels affect myelin dimensions across the lifespan and how resident glial cells may respond to such changes are unknown. Here, to investigate these questions, we used enhancer‐edited mouse lines that accumulate Mbp mRNA levels ranging from 8% to 160% of wild type. In young mice, reduced Mbp mRNA levels resulted in corresponding decreases in Mbp protein accumulation and myelin sheath thickness, confirming the previously demonstrated rate‐limiting role of Mbp transcription in the control of initial myelin synthesis. However, despite maintaining lower line specific Mbp mRNA levels into old age, both MBP protein levels and myelin thickness improved or fully normalized at rates defined by the relative Mbp mRNA level. Sheath length, in contrast, was affected only when mRNA levels were very low, demonstrating that sheath thickness and length are not equally coupled to Mbp mRNA level. Striking abnormalities in sheath structure also emerged with reduced mRNA levels. Unexpectedly, an increase in the density of all glial cell types arose in response to reduced Mbp mRNA levels. This investigation extends understanding of the role MBP plays in myelin sheath elaboration, architecture, and plasticity across the mouse lifespan and illuminates a novel axis of glial cell crosstalk.
