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PubMedDate not supplied

Axons of sacral preganglionic neurons in the cat: II. Axon collaterals.

Axon collaterals were identified in 21 of 24 preganglionic neurons in the lateral band of the sacral parasympathetic nucleus of the cat. Following the intracellular injection of HRP or neurobiotin the axons from 20 of these neurons were followed and 53 primary axon collaterals were found to originate from unmyelinated segments and from nodes of Ranvier. Detailed mapping done in the five best labeled cells showed bilateral axon collaterals distributions up to 25,000 microm in length with 950 varicosities and unilateral distributions up to 12,561 microm with 491 varicosities. The axon collaterals appeared to be unmyelinated, which was confirmed at EM, and were small in diameter (average 0.3 microm). Varicosities were located mostly in laminae I, V, VII, VIII and X and in the lateral funiculi. Most varicosities were not in contact with visible structures but some were seen in close apposition to Nissl stained somata and proximal dendrites. Varicosities had average minor diameters of 1.3 microm and major diameters of 2.3 microm. Most were boutons en passant while 10-20% were boutons termineaux. EM revealed axodendritic and axoaxonic synapses formed by varicosities and by the axons between varicosities. It is estimated that the most extensive of these axon collaterals systems may contact over 200 spinal neurons in multiple locations. These data lead to the conclusion that sacral preganglionic neurons have multiple functions within the spinal cord in addition to serving their target organ. As most preganglionic neurons in this location innervate the urinary bladder, it is possible that bladder preganglionic neurons have multiple functions.

Animals↗
PubMed2006

Dynein mediates retrograde neurofilament transport within axons and anterograde delivery of NFs from perikarya into axons: regulation by multiple phosphorylation events.

We examined the respective roles of dynein and kinesin in axonal transport of neurofilaments (NFs). Differentiated NB2a/d1 cells were transfected with green fluorescent protein-NF-M (GFP-M) and dynein function was inhibited by co-transfection with a construct expressing myc-tagged dynamitin, or by intracellular delivery of purified dynamitin and two antibodies against dynein's cargo domain. Monitoring of the bulk distribution of GFP signal within axonal neurites, recovery of GFP signal within photobleached regions, and real-time monitoring of individual NFs/punctate structures each revealed that pertubation of dynein function inhibited retrograde transport and accelerated anterograde, confirming that dynein mediated retrograde axonal transport, while intracellular delivery of two anti-kinesin antibodies selectively inhibited NF anterograde transport. In addition, dynamitin overexpression inhibited the initial translocation of newly-expressed NFs out of perikarya and into neurites, indicating that dynein participated in the initial anterograde delivery of NFs into neurites. Delivery of NFs to the axon hillock inner plasma membrane surface, and their subsequent translocation into neurites, was also prevented by vinblastine-mediated inhibition of microtubule assembly. These data collectively suggest that some NFs enter axons as cargo of microtubues that are themselves undergoing transport into axons via dynein-mediated interactions with the actin cortex and/or larger microtubules. C-terminal NF phosphorylation regulates motor association, since anti-dynein selectively coprecipitated extensively phosphorylated NFs, while anti-kinesin selectively coprecipitated less phosphorylated NFs. In addition, however, the MAP kinase inhibitor PD98059 also inhibited transport of a constitutively-phosphorylated NF construct, indicating that one or more additional, non-NF phosphorylation events also regulated NF association with dynein or kinesin.

Animals↗
PubMed1988

Fast axonal transport alterations in amyotrophic lateral sclerosis (ALS) and in parathyroid hormone (PTH)-treated axons.

Video-enhanced contrast techniques have been used to study fast axonal transport of organelles in diseased and normal human axons. A broad perspective on the importance of axonal transport in the pathogenesis of human neurological disorders is presented and problems in dealing with human nerve summarized. Results from analysis of organelle traffic in axons from motor nerve in patients with amyotrophic lateral sclerosis (ALS) show: 1) higher mean speed of anterograde organelles, 2) lower mean speed of retrograde organelles, and 3) lower retrograde organelle traffic density. Hyperparathyroidism, another human clinical syndrome, can mimic ALS. The effect of parathyroid hormone (PTH) on axons in vitro is to increase the mean speed of both anterograde and retrograde organelle traffic. The dose response curve and time course of the PTH effect are delineated. Dihydropyridine calcium channel antagonists block the PTH effect, implicating extracellular calcium in the alteration of organelle traffic speed. The results are discussed in relation to neuronal function and the regulation of fast axonal transport.

Amyotrophic Lateral Sclerosis↗
PubMed1997

The axon as a metabolic compartment: protein degradation, transport, and maximum length of an axon.

We present a model that predicts the maximum axonal length from the apparent velocity of slow axonal transport and cytoskeletal protein half-life. The model assumes that in mature axons the apparent velocity of slow transport varies with position, but that the density of cytoskeletal proteins and protein degradation are uniform. The model predicts that the apparent transport velocity of cytoskeletal proteins if highest near the cell body and decreases linearly along the axon, and that when axons branch the apparent velocity of transport decreases across the branch point. The predictions of this model are shown to be consistent with experiments. These results explain the variation in these fundamental metabolic parameters in different axons and species.

Animals↗
PubMedDate not supplied

Axon-myelin transfer of phospholipids and phospholipid precursors. Labeling of myelin phosphoinositides through axonal transport.

Previous studies have provided evidence for axon-to-myelin transfer of intact lipids and lipid precursors for reutilization by myelin enzymes. Several of the lipid constituents of myelin showed significant contralateral/ipsilateral ratios of incorporated radioactivity, indicative of axonal origin, whereas proteins and certain other lipids did not participate in this transfer-reutilization process. The present study will examine the labeling of myelin phosphoinositides by this pathway. Both 32PO4 and [3H]inositol were injected monocularly into 7-9-wk-old rabbits and myelin was isolated 7 or 21 days later from pooled optic tracts and superior colliculi. In total lipids 32P counts of the isolated myelin samples showed significant contralateral/ipsilateral ratios as well as increasing magnitude of contralateral-ipsilateral differences during the time interval. Thin-layer chromatographic isolation of the myelin phosphoinositides revealed significant 32P-labeling of these species, with PIP and PIP2 showing time-related increases. This resembled the labeling pattern of the major phospholipids from rabbit optic system myelin in a previous study and suggested incorporation of axon-derived phosphate by myelin-associated enzymes. The 32P label in PI, on the other hand, remained constant between 7 and 21 days, suggesting transfer of intact lipid. This was supported by the labeling pattern with [3H]inositol, which also showed no increase over time for PI. These results suggest axon-myelin transfer of intact PI followed by myelin-localized incorporation of axon-derived phosphate groups into PIP and PIP2. The general topic of axon-myelin transfer of phospholipids and phospholipid precursors is reviewed.

Animals↗
PubMed1977

Release of protein from axons during rapid axonal transport: an in vitro preparation.

An in vitro system from the frog was used to study fast axonal transport and determine if transported protein is released from the axons. This preparation included the eighth and ninth dorsal root ganglia with their roots, sciatic nerve and gastrocnemius muscle. The preparation was placed in three-compartment chamber with each compartment separated by a silicone grease barrier. The dorsal root ganglia were incubated in [14C]leucine for 5 h in compartment A. The labeled protein was transported down the axon from compartment A to compartment B. The sciatic nerve in compartment B was superfused with frog Ringer. This solution was collected in hourly samples and dialyzed to remove unincoprorated leucine before counting. Incubating the ganglia in 100 microng/ml cycloheximide in frog Ringer blocked the release of labeled protein from the axon. Superfusing compartment B with solution containing 100 microng/ml cycloheximide inhibited axonal and Schwann cell protein synthesis, but did not block the release of labeled protein. It was concluded that the labeled protein released into the superfusing solution was synthesized in the ganglia and transported to the axon before release. SDS acrylamide gels were used to separate the labeled proteins. Sectioning the gels in 2 mm slices and determining the radioactivity showed that 80-85% of the counts were contained in two fast moving bands.

Animals↗
PubMed1983

Axon-myelin transfer of glycerol-labeled lipids and inorganic phosphate during axonal transport.

Axon-to-myelin transfer of lipids precursors have been studied in the rabbit optic system by intraocular injection of [32P]orthophosphate, [14C]glycerol and [3H]glycerol. Choline and ethanolamine phosphoglycerides and myelin showed increasing [32P]-radioactivity between 7 and 21 days following injection, while [3H]- and [14C]-radioactivities remained relative constant. The latter radioactivities decreased, however, in all the axon- and axolemma-enriched fractions during the same period. These findings supported the concept that a portion of substances undergoing axonal transport enters the pool of myelin lipids by two mechanisms: transcellular transfer of intact lipid and axon-myelin transfer of precursors which are re-utilized for lipid biosynthesis by myelin-localized enzymes. The present study shows that inorganic phosphate, possibly generated by catabolic activity within the axon, is able to enter myelin and participate in the re-utilization mechanism as previously described for serine, choline and acyl chains. The relative invariance of the 3H:14C ratio suggested that the majority of glycerol is not re-utilized in this manner but probably enters myelin through transfer of intact lipid. These and earlier results suggest a possible form of metabolic dependence of myelin on tropine substances from the axon.

Animals↗
PubMed1984

Localization of axonally transported label in chick retinal ganglion cell axons after intravitreal injections of wheat germ agglutinin conjugated to horseradish peroxidase.

We have studied the subcellular localization of peroxidase-labeled organelles after anterograde axonal transport by chick retinal ganglion cells that had been exposed 23-25 h earlier to wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). After intravitreal injection of WGA-HRP, we found in the optic tectum that 82% of labeled organelles were located within axons and axon terminals. The organelles included: tubules and cisternae of the smooth endoplasmic reticulum, hypolemmal cisternae, vesicles, dense bodies and multivesticular bodies. We also measured the distances between the centers of the labeled organelles and the plasma membrane of these profiles. The density of organelles (number of organelles/micron 2) was plotted as a function of distance from the plasma membrane. Irrespective of the dose of lectin-peroxidase injected, labeled organelles were most densely concentrated in a 30 nm wide annular zone centered 75 nm in from the plasma membrane. In axon terminals the labeled organelles were most concentrated 75-90 nm in from the plasma membrane. Assuming that the peroxidase label indicates the presence of WGA-HRP, we conclude that after anterograde axonal transport the lectin accumulates in lysosomal organelles and elements of the smooth endoplasmic reticulum. Therefore, in contrast to the more restricted localization of [125I]WGA as inferred from electron microscopic autoradiography after uptake and transport by the same cell type, WGA-HRP-labeled organelles are found more diffusely within the axoplasm, particularly in axon terminals. Furthermore, peroxidase-labeled organelles in dendritic, glial or neuronal cell bodies in the tectum were seen less frequently than expected based on evidence of frequent transfer to second cells after intravitreal injections of [125I]WGA. Thus, we infer that at these concentrations WGA labeled with HRP may not be transferred intercellularly as efficiently as even lower concentrations of iodinated WGA are apparently transferred.

Animals↗
PubMed1988

Topographic sequence of outgrowth of corticospinal axons in the rat: a study using retrograde axonal labeling with Fast blue.

The retrogradely transported dye, Fast blue, was injected into cervical or lumbar segments of the spinal cord of rats during the first days of life in order to label the cell bodies of origin of the corticospinal tract which is growing down the cord during that period. The first corticospinal axons arrive at cervical levels immediately after birth and all arise from a circumscribed group of layer V pyramidal cells in a small region of dorsal parietal cortex. This same cell group provides the corticospinal projection to lumbar segments of the spinal cord, the axons reaching those segments at the end of the first postnatal week. The area of lumbar projecting cells undergoes relatively little expansion and no diminution during subsequent weeks and into adulthood. The area occupied by cortical cells projecting to the spinal cord expands during the first postnatal week, but the axons of all these additional cells do not appear to invade the lower sequents of the spinal cord. By the end of the first week, corticospinal cells can be labeled in a continuous sheet throughout most of the extent of the frontal, parietal and cingulate cortex. During the second and third postnatal weeks, the area sending axons to the upper levels of the spinal cord diminishes and large areas bereft of retrogradely labeled corticospinal cells appear: laterally, in lateral frontal and lateral parietal cortex; dorsally, at the border of frontal and parietal cortex; medially, in medial frontal and cingulate cortex. The more restricted adult pattern is established at the end of the third week. Hence, the first cortical axons to advance down the spinal cord are those that will innervate the lumbar segments in the adult. Later addition of corticospinal axons involves only those projecting to upper cord segments. Within this group there are those which will establish persistent connections from appropriate cortical areas and others that will shortly be eliminated from inappropriate areas.

Aging↗
PubMed1981

Axonally transported proteins associated with axon growth in rabbit central and peripheral nervous systems.

In an effort to determine whether the "growth state" and the "mature state" of a neuron are differentiated by different programs of gene expression, we have compared the rapidly transported (group I) proteins in growing and nongrowing axons in rabbits. We observed two polypeptides (GAP-23 and GAP-43) which were of particular interest because of their apparent association with axon growth. GAP-43 was rapidly transported in the central nervous system (CNS) (retinal ganglion cell) axons of neonatal animals, but its relative amount declined precipitously with subsequent development. It could not be reinduced by axotomy of the adult optic nerves, which do not regenerate; however, it was induced after axotomy of an adult peripheral nervous system nerve (the hypoglossal nerve, which does regenerate) which transported only very low levels of GAP-43 before axotomy. The second polypeptide, GAP-23 followed the same pattern of growth-associated transport, except that it was transported at significant levels in uninjured adult hypoglossal nerves and not further induced by axotomy. These observations are consistent with the "GAP hypothesis" that the neuronal growth state can be defined as an altered program of gene expression exemplified in part by the expression of GAP genes whose products are involved in critical growth-specific functions. When interpreted in terms of GAP hypothesis, they lead to the following conclusions: (a) the growth state can be subdivided into a "synaptogenic state" characterized by the transport of GAP-23 but not GAP-43, and an "axon elongation state" requiring both GAPs; (b) with respect to the expression of GAP genes, regeneration involves a recapitulation of a neonatal state of the neuron; and (c) the failure of mammalian CNS neurons to express the GAP genes may underly the failure of CNS axons to regenerate after axon injury.

Animals↗
PubMedDate not supplied

The pathogenesis of reactive axonal swellings: role of axonal transport.

The role of axonal transport in the pathogenesis of the axonal swellings which develop at the severed ends of transected axons was studied by electron microscopic (EM) autoradiography. Proteins carried by fast anterograde transport in rat sciatic nerves were labeled with [3H]-leucine or [3H]-fucose; [3H]-leucine, [3H]-fucose, and [125I]-tetanus toxin were used to label components of retrograde transport. After the labeling procedure, the nerves were ligated and 2 to 24 hours later the animals were perfused with fixatives. The axonal swellings in both the proximal and distal stumps contained densely packed membranous organelles. The transported radioactivity in the swellings was strictly associated with these organelles, particularly pleomorphic vesicles and branched tubules derived from smooth endoplasmic reticulum. The endogenous (tritiated) substances had a similar association with the organelle collections in both the proximal stump (fast anterograde transport) and in the distal stump (retrograde transport). The exogenous marker of retrograde transport (125I-tetanus toxin) had the same autoradiographic localization. These results suggest that fast anterograde and retrograde transport are very similar processes carrying predominantly membranous organelles and constituting a system of bidirectional fast transport. The accumulations of organelles in reactive swellings are interpreted as the consequence of the acute focal interruption of this system. Studies of axonal transport provide a means for investigation of the origin and fate of axonal organelles in pathologic processes.

Animals↗
PubMed1991

A calmodulin inhibitor with high specificity, compound 48/80, inhibits axonal transport in frog nerves without disruption of axonal microtubules.

The calmodulin inhibitor compound 48/80 has previously been shown to arrest axonal transport in vitro in the regenerating frog sciatic nerve. The inhibition was limited to the outgrowth region of nerves, which had been allowed to regenerate in vivo for 6 days after a crush lesion, before they were incubated with or without drugs in vitro overnight. The effects of compound 48/80 on the regenerating nerve were further investigated. A concentration of compound 48/80 (50 micrograms ml-1), which effectively inhibits axonal transport, did not cause observable changes of the microtubules of regenerating axons in the outgrowth region as judged by electron microscopy. Furthermore, it was shown that also a lower concentration (25 micrograms ml-1) inhibited axonal transport. As a measure of possible metabolic effects, the level of ATP was assessed in the regenerating nerve after exposure to compound 48/80. Compound 48/80 at 25 micrograms ml-1 did not change the level of ATP in the nerve. The assembly of bovine brain microtubule proteins in a cell-free system was unaffected by 25 micrograms ml-1 of compound 48/80 and slightly inhibited by 50 micrograms ml-1. At higher concentrations (greater than 100 micrograms ml-1) assembly of microtubules appeared stimulated, and microtubule spirals as well as closely aligned microtubules could be seen. These effects appeared to be unrelated to the transport effects. The present results indicate that compound 48/80 arrests axonal transport via mechanisms other than destruction of axonal microtubules or interference with the energy metabolism. It is possible that these mechanisms involve inhibition of calmodulin-regulated events essential to the transport.

Adenosine Triphosphate↗
PubMed1987

Axonal tubulin and microtubules: morphologic evidence for stable regions on axonal microtubules.

Biochemical studies indicate that axonal tubulin is composed of at least two distinct pools that differ in cold solubility and biochemical composition [Brady et al: J. Cell Biol. 99:1716-1724]. To determine the morphologic correlate of cold-insoluble tubulin, segments of rat optic nerves were exposed to a series of in vitro experimental conditions that affect microtubules (MTs), including cold, podophyllotoxin (PT), triflupromazine (TFP), and taxol, and then examined by electron microscopy. Longitudinal sections of control axons showed MTs oriented parallel to the long axis of the axons. Axons exposed to cold, PT, and TFP showed short segments of MTs in association with cytoskeletal disarray. Morphometric studies were used to distinguish between a simple malorientation of MTs (undulation or zigzags in their course) and the loss of labile segments of MTs, leaving the stable portions behind. The lengths of MT segments were measured in longitudinal sections, and the numbers of MTs were determined in the cross sections. All MT segment-length histograms showed a unimodal distribution. Cold and PT produced a simple shift of the control histogram to the shorter length MTs. In cross sections the numbers of MTs in cold- and PT-exposed axons were significantly decreased, indicating that the presence of short segments of MTs in the longitudinal plane of sections was due to a loss of portions of MTs. Taxol, an agent that promotes MT assembly, reversed the cold effect partially and resulted in increases in both MT segment length and number. These studies indicate that stable MT segments are portions of longer MTs containing both stable and labile regions. Furthermore, these findings are consistent with the hypothesis that cold-insoluble tubulin functions as a transportable MT-organizing complex in the axon.

Alkaloids↗
PubMed1993

The protein phosphatase inhibitor okadaic acid increases axonal neurofilaments and neurite caliber, and decreases axonal microtubules in NB2a/d1 cells.

When cells were treated with dbcAMP for 3 days to induce the outgrowth of axonal neurites, the addition of the phosphatase inhibitor okadaic acid (OA; 5 nM) for the last 24 hr markedly increased neurofilament subunit immunoreactivity including phosphate-dependent NF-H epitopes in axonal neurites, increased axonal neurite caliber by approximately 30%, but did not increase neurite contour length. Ultrastructural analysis demonstrated a > 2-fold increase in neurofilaments and indicated that neurofilaments were phosphorylated to a similar extent in the presence and absence of OA. Vimentin immunoreactivity, which undergoes down-regulation during dbcAMP-mediated differentiation, was not increased by OA. OA did not induce the precocious appearance of delayed phosphate-dependent neurofilament epitopes suggesting that it did not induce the activation of additional neurofilament kinases. NF-H subunits from cytoskeletons of OA-treated cells were less susceptible to degradation by an endogenous calcium-dependent protease, providing a possible mechanism for neurofilament accumulation during OA treatment. By contrast, OA decreased axonal neurite microtubules, and eliminated stabilized (acetylated) axonal microtubules. OA treatment at earlier times prevented and reversed neurite outgrowth. Despite increased deposition of phosphorylated neurofilaments, OA did not hasten the development of colchicine resistance to neurites, suggesting that stabilization of the axonal cytoskeletal lattice requires neurofilament-microtubule interaction.

Animals↗
PubMed2001

Pathfinding by sensory axons in Drosophila: substrates and choice points in early lch5 axon outgrowth.

We have examined the pattern of axon growth from the lateral chordotonal (lch5) neurons in the body wall of the Drosophila embryo and identified cellular substrates and choice points involved in early axon pathfinding by these sensory neurons. At the first choice point (TP1), the lch5 growth cones contact the most distal cells of the spiracular branch (SB) of the trachea. The SB provides a substrate along which the axons extend internally to the level of the intersegmental nerve (ISN). In the absence of the SB, the lch5 axons often stall near TP1 or follow aberrant routes towards the CNS. At the second choice point (TP2), the lch5 growth cones make their first contact with other axons and turn ventrally toward the CNS, fasciculating specifically with the motor axons of the ISN.

Animals↗
PubMed1993

An analysis of HRP-filled basket cell axons in the cat's cerebellum. II. Axonal distribution.

The axons of basket cells course horizontally within the lower molecular layer of the cerebellar cortex and give rise to three types of axon collaterals. One collateral distributes around the somata and axon hillocks of Purkinje cells, forming a complex pericellular basket-like formation or "pinceau". The other two axonal specializations have the form of beaded tendrils, but differ in their origin and laminar distribution. In the previous paper, the morphometry and configuration of these axonal branches were described. In the present account, their synaptic relationships are analyzed based on serial section analysis and computer reconstructions. Our data indicate that: (1) Purkinje cells receive descending collaterals from more than one basket cell; (2) the contribution of the descending collaterals to individual pinceau is not uniform; Purkinje cells located close to the basket cell of origin receive a greater number of descending collaterals when compared to Purkinje cells located more distally; (3) few synaptic junctions are formed by the descending collaterals within the pinceaux; (4) beaded tendrils make synaptic contacts with the somata and dendrites of Purkinje cells, and (5) the horizontal axon forms synaptic junctions with the dendritic shafts and spiny branchlets of Purkinje cells. Functional considerations of these synaptic relationships are discussed in the light of the classic concept of off-beam inhibition mediated by basket cells.

Animals↗
PubMed1993

Axons and axon terminals of cerebellar Purkinje cells and basket cells have higher levels of parvalbumin immunoreactivity than somata and dendrites: quantitative analysis by immunogold labeling.

The immunointensities of calcium-binding proteins parvalbumin (PV) and calbindin D28K were quantified in different parts of Purkinje cells and interneurons (basket cells and stellate cells) of the rat cerebellum. An electron microscopic, postembedding immunogold procedure on Lowicryl K4M-embedded thin sections was applied. Neuronal profiles were identified by double-labeling immunocytochemistry using the combination of the two primary antibodies, mouse monoclonal anti-rat calbindin D28K and rabbit polyclonal anti-rat PV. The secondary antibodies were conjugated with colloidal gold of different sizes (10 and 15 nm diameter). In the cerebellar cortex, double-labeled profiles were identified as Purkinje cells and profiles labeled only with anti-PV were identified as inteneurons. The densities of gold particles were used for statistical comparison of the relative levels of PV and calbindin D28K in somata, dendrites, dendritic spines, axons and axon terminals of Purkinje cells, and interneurons. The axons and axon terminals of Purkinje cells and basket cells had significantly higher levels of PV immunoreactivity than Purkinje cell somata, primary, secondary, and tertiary dendrites, and dendritic spines, as well as interneuron somata. On the other hand, the present study could not determine conclusively whether calbindin D28K was distributed homogeneously throughout soma, dendrites, and axons of Purkinje cells or was also concentrated in Purkinje cell axons. To estimate absolute PV concentrations, we made a series of artificial standard samples which were aldehyde-fixed 10% bovine serum albumin containing given concentrations of PV (0, 12.5, 25, 50, 100, 200, and 400 microM, 1 and 2 mM), and calibration curves were deduced from quantitative immunogold analyses of these standard samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Calcitonin gene-related peptide- and substance P-immunoreactive axons in the nucleus gracilis of the rat with special reference to axonal dystrophy: light and electron microscopic observations.

Calcitonin gene-related peptide (CGRP) and substance P (SP)-immunoreactive (IR) axons in the nucleus gracilis of normal rats (1-15 months of age) were studied by light and electron microscopy. Besides many CGRP-IR and SP-IR varicosities with normal appearance, we found a few swollen (nearly round or oval) varicosities with either CGRP or SP immunoreactivity. Swollen CGRP-IR varicosities were more frequently seen than SP-IR ones, appearing from 3 months of age and increasing in number and size (up to approximately 25 microns in diameter) with advancing age. At the electron microscopic (EM) level, CGRP-IR and SP-IR swollen varicosities showed dystrophic changes, i.e., many membranous dense bodies, and proliferation of microtubules and neurofilaments. CGRP-IR or SP-IR dystrophic axons also contained many mitochondria and sometimes made synaptic contacts with nonreactive dendrites (occasionally with non-IR axons). These findings suggest that the dystrophic CGRP and SP axonal profiles represent a functionally distinct subpopulation of axonal dystrophy in the nucleus gracilis and use CGRP or SP as a neuroactive substance. Using a double-immunostaining method, many of normal CGRP-IR axons were identified to be SP-IR. However, no single dystrophic varicosity was found to contain both CGRP and SP immunoreactivities. These findings suggest that CGRP and SP afferents are independently affected and progress to dystrophic changes.

Animals↗