Proportion Of Unmyelinated Axons Research Articles

The number, size, and type of axons in rat subcortical white matter on left and right sides: A stereological, ultrastructural study

Abundant evidence indicates important functional differences between the two cerebral hemispheres of humans, although the cellular basis of these differences is unknown. A recent hypothesis proposes that these functional differences depend on differences between sides in the "repertoire" of axonal conduction delays for cortico-cortical axons. In morphological terms this corresponds to differences in caliber, or proportion, of myelinated versus unmyelinated axons. Several behavioural studies have indicated that cerebral asymmetry occurs in rodents, in which rigorous morphological analysis is possible. The hypothesis was therefore tested for the first time in adult male Wistar rats, using transmission electron microscopy and stereological methods. Subcortical white matter was compared between left and right sides in three regions (frontal, parietal, and occipital). The average caliber and numerical density of unmyelinated and myelinated axons was compared between sides and between regions. All data were corrected for shrinkage. No significant differences between sides were found in the average caliber of either type of axon in any region. The numerical density of either type of axon also yielded no significant differences between sides in any region. Significant differences were evident between regions in both caliber and numerical density of the two axonal types, and these quantitative data are reported. The proportion of unmyelinated axons in the lateral white matter was also higher than in previous studies of hemispheric white matter that studied the corpus callosum. The present study provides no evidence supporting the hypothesis that functional hemispheric specialization is due to differences in axonal number, caliber or type.

Ultrastructural analysis of NMDA, AMPA, and kainate receptors on unmyelinated and myelinated axons in the periphery.

The present study determines the proportions of unmyelinated cutaneous axons at the dermal-epidermal junction in glabrous skin and of myelinated and unmyelinated axons in the sural and medial plantar nerves that immunostain for subunits of the ionotropic glutamate receptors. Approximately 20% of the unmyelinated cutaneous axon profiles at the dermal-epidermal junction immunostain for either N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or kainate receptor subunits. These findings are consistent with previous observations that NMDA and non-NMDA antagonists ameliorate nociceptive behaviors that result from noxious peripheral stimulation. In the sural nerve, where the large majority of myelinated fibers are sensory, approximately half of the myelinated axon profiles immunostain for the NMDA receptor 1 (R1) subunit, 28% immunostain for the glutamate receptor 1 (GluR1) AMPA subunit, and 11% for the GluR5,6,7 kainate subunits. Even higher proportions immunostain for these receptors in the medial plantar nerve, a mixed sensory and motor nerve. In the sural nerve, 20% of the unmyelinated axon profiles immunostain for NMDAR1 and only 7% label for GluR1 or GluR5,6,7. Because the sural nerve innervates hairy skin, these data suggest that glutamate will activate a higher proportion of unmyelinated axons in glabrous skin than in hairy skin. Measurements of fiber diameters indicate that all sizes of myelinated axon profiles, including Adelta and Abeta, are positively labeled for the ionotropic receptors. The presence of glutamate receptors on large-diameter myelinated axons suggests that these mechanosensitive receptors, presumably transducing touch and pressure, may also respond to local glutamate and thus be chemosensitive.

Myelin associated glycoprotein modulates glia-axon contact in vivo.

Myelin-associated glycoprotein (MAG) was postulated to play an important role in myelination. However, we showed previously that MAG null mutants exhibited no gross abnormality in myelination. Ultrastructural studies revealed subtle alterations in periaxonal organisation, indicating a restricted structural role for MAG in the formation and maintenance of periaxonal structures (Li et al., 1994). Here we show that myelination in MAG deficient mice is not as finely controlled as it is in wild type mice. The abnormalities manifest themselves as a decrease in the proportion of myelinated axons and a reciprocal increase in the proportion of unmyelinated axons in mutants' optic nerves. In addition, dysregulated myelination is occasionally observed in the form of multiply myelinated fibres, grouping of myelinated axons and myelin debris by a large myelin sheath, redundant myelin loops and, very rarely, massive myelin surrounding relatively small axons. Thus, in the absence of MAG, some glial cells seem unable to determine when, where and how much myelin should be laid down. These data support the notion of MAG being a glial recognition/adhesion molecule. A model is proposed regarding the roles MAG could play in the formation and maintenance of myelin structure.

Structural development of the feline mental nerve.

The qualitative and quantitative structural development of the feline mental nerve (MN), a branch of the inferior alveolar nerve (IAN), was studied by electron microscopy from 40 days postconception (dpc) (about 2 weeks before birth) to 11 years after birth. Myelination was initiated at 40-45 dpc. At 2 months after birth de novo myelination was completed, and the larger myelinated axons had achieved a fully differentiated nodal-paranodal morphology. Size growth of myelinated axons continued until 6 months, when a bimodal size distribution between 1 and 12 months was established. When compared to the IAN, the MN contained a higher proportion of unmyelinated axons. Age-related signs of axon degeneration, which previously were recorded in the IAN, were lacking in the MN. This suggests that senescent IAN axon degeneration is related to dental rather than to cutaneous MN branches.

Proportion of unmyelinated axons in the rat inferior alveolar nerve and mandibular molar pulps after neonatal administration of capsaicin

Neonatal rats were given capsaicin subcutaneously. Controls received vehicle only. Six months later the nerve fiber populations in the dorsal root L4, in the inferior alveolar nerve and in mandibular molar pulps were examined by electron microscopy. The proportion of unmyelinated axons was found to be markedly decreased in root and nerve specimens from capsaicin-treated rats. However, the pulpal nerves in tooth specimens from these rats showed no obvious alterations.

The distribution of nodal sprouts in a paralysed or partly denervated mouse muscle

The right gluteus maximus muscles of young adult mice were paralysed with botulinum toxin for up to 21 days or partly denervated by spinal root section for up to 63 days; the intramuscular and extramuscular nerves were then examined in the electron microscope in thin sections of tissue fixed conventionally or stained with zinc iodide-osmium tetroxide. Contralateral muscles were also examined as controls. The distribution of nodal sprouts in the nerves of the paralysed or partly denervated muscles was determined by calculating the mean ratios of unmyelinated to myelinated axons in nerve profiles containing different numbers of myelinated axons (intact or degenerating) and comparing these with control ratios. In paralysed muscles there was a significantly higher proportion of nerve profiles containing one or two unmyelinated axons alongside a single myelinated axon. Nerve profiles containing two or more myelinated axons did not show any increase in the proportion of unmyelinated axons. Thus, there is probably nodal sprouting in paralysed muscles which is restricted to the most distal nodes of the intramuscular nerves. In muscles partly denervated for 8 days there were significant increases in the proportion of unmyelinated axons in nerve profiles which had contained up to 5–10 myelinated axons. After 21 days of partial denervation, similar increases may have occurred in the larger intramuscular nerve profiles and after 63 days there were large increases in the proportion of unmyelinated axons in the main intramuscular nerve branches and in the extramuscular nerve. Nodal sprouting in response to partial denervation is therefore localised initially to the smaller, more distal nerve branches; at later times, some sprouts probably grow slowly in a disto-proximal direction along denervated Schwann cell pathways. The existence of nodal sprouts in paralysed muscles and their restricted distribution in paralysed and partly denervated muscles suggest that the nodal sprouting stimulus is produced by the muscle and acts only at distal nodes.