Morphometric and ultrastructural changes with ageing in mouse peripheral nerve

Abstract

Qualitative and quantitative information is reported on the morphological changes that occur in nerve fibres and nonneuronal cells of peripheral nerve during the lifetime of the mouse. Tibial nerves of mice aged 6-33 mo were studied. With ageing, collagen accumulates in the perineurium and lipid droplets in the perineurial cells. Macrophages and mast cells increase in number, and onion bulbs and collagen pockets are frequently present. Schwann cells associated with myelinated fibres (MF) slightly decrease in number in parallel with an increase of the internodal length from 6 to 12 mo, but increase in older nerves when demyelination and remyelination are common. The unmyelinated axon to myelinated fibre (UA\MF) ratio was about 2 until 12 mo, decreasing to 1.6 by 27 mo. In older mice, the loss of nerve fibres involves UA (50 % loss of 27-33 mo cf. 6 mo) more markedly than MF (35 %). In aged nerves wide incisures and infolded or outfolded myelin loops are frequent, resulting in an increased irregularity in the morphology of fibres along the internodes. In the mouse there is an adult time period, 12-20 mo, during which several features of degeneration progressively appear, and an ageing period from 20 mo upwards when the nerve suffers a general disorganisation and marked fibre loss.

Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

“…Indeed, the lower density of immunolabeled TRPV1-positive fibers in tibial and cutaneous nerves would support this possibility. However, anatomical studies have indicated that loss of afferents in the skin becomes most prominent only in very old animals [13]. Only a modest afferent loss would therefore be expected at 15 months of age, the time at which a reduction in TRPV1 protein was measured in this study.…”

“…Functional studies in several species have shown that impairment of cutaneous sensitivity occurs with aging [13,37]. This age-related decrease in sensitivity can reduce tactile perception, detection of noxious stimuli and tissue injury.…”

“…In humans, electrophysiological measures have found lower nerve conduction velocity in older individuals, suggesting impairment in axon structure and function [9,37]. Analysis of nerve fibers in aging mice from 20 months of age onward, showed both myelinated and unmyelinated fibers to be reduced in number, which in the very old mouse (33 months) approaches 50% loss [13]. In contrast, mice between 12 and 20 months of age show only mild age-related changes (fiber reduction, myelin loops, membrane irregularity).…”

Absence of Tau triggers age‐dependent sciatic nerve morphofunctional deficits and motor impairment

“…Thus, we monitored myelinated (A‐fibers) density in p‐phenylene diamine (PPD)‐stained sections. In agreement with previous studies (Ceballos et al ., 1999), two‐way ANOVA showed an aging effect [ F 1,16  = 11.71, p = 0.0038] with aged animals exhibiting reduced density of myelinated fibers independently of genotype (p < 0.05 for both genotypes) (Fig. 2A,B).…”

Neural control of aging skeletal muscle

“…Age-related changes in the neuronal soma size (Liu et al ., 1996;Kanda & Hashizume, 1998) and number (Hashizume et al ., 1988;Zhang et al ., 1996;Jacob, 1998) in the spinal cord have been reported. Age-related changes in peripheral nerve have been documented in tibialis nerves of mice aged 6 -33 months (Ceballos et al ., 1999) including accumulation of collagen in the perineurium and lipid droplets in the perineurial cells, together with an increase in the number of macrophages and mast cells. Schwann cells associated with myelinated fibres (MF) decrease slightly in number, in parallel with an increase of the internodal length from 6 to 12 months, but then increase in number in older nerves in parallel with the greater incidence of demyelination and remyelination.…”