The macro and micro-structure of the celiac and cranial mesenteric ganglia in a long-lived rodent - paca (Cuniculus paca, Linnaeus 1766) / La macro y micro estructura de los ganglios mesentéricos celíacos y craneales en un roedor longevo - paca (Cuniculus paca, Linnaeus 1766)

SUMMARY: The celiac, cranial mesenteric and celiacomesenteric ganglia of the paca (Cuniculus paca) were found between the celiac and cranial mesenteric arteries. Two predominant patterns were found: isolated celiac and cranial mesenteric ganglion and the celiacomesenteric ganglion. At the microscopic level, the ganglia are constituted by an agglomeration of neurons surrounded by capsule of connective tissue. Most of these neurons had a single eccentric nucleus. Satellite cells and mast cells were found around the soma. The mast cells were also found ar ound blood vessels and in the capsule of the ganglia.

RESUMEN: Los ganglios celíacos, mesentérico-craneales y celíaco mesentéricos de la paca (Cuniculus paca) se encontraron entre las arterias celíaca y mesentérica craneal. Se visalizaron dos patrones predominantes: celiaca aislada y ganglio mesentérico craneal y ganglio celiaco mesentérico. A nivel microscópico, los ganglios están constituidos por una aglomeración de neuronas rodeadas por una cápsula de tejido conectivo. La mayoría de estas neuronas tenían un solo núcleo excéntrico. Se encontraron células satélites y mastocitos alrededor del soma. Los mastocitos también se encontraron alrededor de los vasos sanguíneos y en la cápsula de los ganglios.

Kinesin-5 is essential for growth-cone turning.

Inhibition of kinesin-5, a mitotic motor protein also expressed in neurons, causes axons to grow faster as a result of alterations in the forces on microtubules (MTs) in the axonal shaft. Here, we investigate whether kinesin-5 plays a role in growth-cone guidance. Growth-cone turning requires that MTs in the central (C-) domain enter the peripheral (P-) domain in the direction of the turn. We found that inhibition of kinesin-5 in cultured neurons prevents MTs from polarizing within growth cones and causes them to grow past cues that would normally cause them to turn. We found that kinesin-5 is enriched in the transition (T-) zone of the growth cone and that kinesin-5 is preferentially phosphorylated on the side opposite the invasion of MTs. Moreover, when a growth cone encounters a turning cue, phospho-kinesin-5 polarizes even before the growth cone turns. Additional studies indicate that kinesin-5 works in part by antagonizing cytoplasmic dynein and that these motor-driven forces function together with the dynamic properties of the MTs to determine whether MTs can enter the P-domain. We propose that kinesin-5 permits MTs to selectively invade one side of the growth cone by opposing their entry into the other side.

Characterization of the adaptor protein ARH expression in the brain and ARH molecular interactions.

Previously, pA134 was identified as one of the mRNAs present in the squid giant axon. Comparative sequence analyses revealed that the pA134 gene product manifested significant similarity to the mammalian lipoprotein receptor adaptor protein also known as ARH (autosomal recessive hypercholesterolemia). ARH mRNA and protein displayed very similar pattern of expression throughout the mouse brain. Significant levels of expression were observed in cells with a predominantly neuronal profile in the cerebellum, brainstem, olfactory bulb, hippocampus, and cortex. A yeast two hybrid screen for ARH protein interactions in mouse brain identified the following binders: amyloid precursor-like protein 1, low density lipoprotein receptor-related protein (LRP) 1, LRP8, and GABA receptor-associated protein-like 1. The interactions of ARH with LRP1 and GABA receptor-associated protein-like 1 were subsequently verified by co-immunoprecipitation of the protein complexes from transfected human embryonic kidney cells. The presence of ARH mRNA in axon of primary sympathetic neurons was established by RT-PCR analyses and confirmed by in situ hybridization. Taken together, our data suggest that ARH is a multifunctional protein whose spectrum of function in the brain goes beyond the traditionally known metabolism of lipoproteins, and that ARH may be locally synthesized in the axon.

Synaptic density, convergence, and dendritic complexity of prevertebral sympathetic neurons.

Prevertebral sympathetic ganglia contain a unique population of final motor neurons receiving convergent synaptic inputs not only from spinal preganglionic neurons, but also from peripheral intestinofugal neurons projecting from the gut. We used quantitative confocal and ultrastructural immunohistochemistry to determine how this increased synaptic convergence is accommodated by sympathetic final motor neurons in the celiac ganglion of guinea pigs. Terminals of intestinofugal neurons were identified by their immunoreactivity to vasoactive intestinal peptide. Stereologic analyses were based on transects and point counts at confocal and ultrastructural levels. The relative amount of dendritic neuropil in the medial regions of the ganglion was approximately 2.5 times greater than in the lateral regions of the ganglion, consistent with the 2 to 3 times difference in average dendritic field size of neurons in these regions. The total numbers of boutons and synaptic profiles showed significant positive correlations with the relative amount of neuropil in a region. However, the overall density of synaptic boutons was twice as high in the medial region of the ganglion compared with the lateral regions. Because the relative density of preganglionic synapses was similar in each region, this difference was due to the selective projection of intestinofugal inputs to neurons in the medial celiac ganglion, where they provided 45% of synaptic contacts. These results show that, compared with vasoconstrictor neurons, sympathetic neurons regulating gastrointestinal activity support a higher number of convergent inputs in two ways: in addition to having larger dendritic fields, they also have a twofold higher density of synapses.

STOP (stable-tubule-only-polypeptide) is preferentially associated with the stable domain of axonal microtubules.

Axonal microtubules consist of two distinct domains that differ in tyrosinated-tubulin staining. One domain stains weakly for tyrosinated-tubulin, while the other stains strongly, and the transition between these domains is abrupt; the tyrosinated-tubulin-poor domain is at the minus end of the microtubule, and the tyrosinated-tubulin-rich domain extends from the plus end of the tyrosinated-tubulin-poor domain to the end of the microtubule. The tyrosinated-tubulin-poor domain is drug- and cold-stable, whereas the tyrosinated-tubulin-rich domain is drug-labile, but largely cold-stable. STOP (stable-tubule-only-polypeptide) has potent microtubule stabilizing activity, and may contribute to the cold and drug stability of axonal microtubules. To evaluate this possibility, we examined STOP association with the different types of microtubule polymer in cultured sympathetic neurons. By immunofluorescence, STOP is present in the cell body and throughout the axon; axonal staining declines progressively in the distal portion of the axon, and reaches lowest levels in the growth cone. Growth cone microtubules, which are drug and cold labile, do not stain detectably for STOP. To examine individual axonal microtubules for STOP, we used a procedure that causes microtubules to splay out from the main axonal array so that they can be visualized for relatively long distances along their length. Both tyrosinated-tubulin-rich and tyrosinated-tubulin-poor polymer stain for STOP, but STOP is several-fold more concentrated on tyrosinated-tubulin-poor polymer than on tyrosinated-tubulin-rich polymer. These results are consistent with STOP dependent stabilization of axonal microtubules, with the difference between cold-stable polymer versus cold- + drug-stable polymer determined by the amount of STOP on the polymer.

Development of convergent synaptic inputs to subpopulations of autonomic neurons.

Visceromotor neurons in mammalian prevertebral sympathetic ganglia receive convergent synaptic inputs from spinal preganglionic neurons and peripheral intestinofugal neurons projecting from the enteric plexuses. Vasomotor neurons in the same ganglia receive only preganglionic inputs. How this pathway-specific pattern of connectivity is established is unknown. We have used a combination of immunohistochemical, ultrastructural, and electrophysiological techniques to investigate the development of synaptic inputs onto visceromotor and vasomotor neurons in the celiac ganglion of guinea pigs. Functional synaptogenesis occurred primarily from early fetal (F30-F35) to midfetal (F36-F45) stages, after the neurochemical differentiation of vasomotor and visceromotor neurons but before establishment of their electrophysiological phenotypes. Intestinofugal inputs were detected only on presumptive visceromotor neurons located primarily in medial regions of the ganglion. The number of ultrastructurally identified synaptic profiles increased in parallel with functional synaptogenesis, especially in medial regions, where dendritic growth rates also were higher. However, the expression of immunoreactivity to choline acetyltransferase in the terminals of inputs was very low until late fetal stages, after functional transmission already had been established. These results show that peripheral intestinofugal neurons directly establish appropriate functional connections with their target visceromotor neurons simultaneously with the development of functional preganglionic inputs to both visceromotor and vasomotor neurons. It seems likely that synaptogenesis occurs independently of the neurochemical differentiation of the target neurons but is closely related to the pathway-specific dendritic development of those neurons.

Constitutive expression of the 27-kDa heat-shock protein in neurons and satellite cells in the peripheral nervous system of the rat.

By use of reverse transcriptase-polymerase chain reaction, abundant expression of the mRNA of 27 kDa heat shock protein (Hsp27) was revealed in the sympathetic and parasympathetic ganglia as well as in the sensory ganglia of unstressed adult rats. In situ hybridization and immunohistochemistry further localized Hsp27 mRNA and protein to both neurons and satellite cells in all types of ganglia examined. Schwann cells in the ganglia and peripheral nerve fibers were devoid of Hsp27 signal. These results suggested that Hsp27 is constitutively expressed in neurons and satellite cells in the entire peripheral nervous system of the rat.

Integrin alpha1 localization in murine central and peripheral nervous system.

The distribution of neurons expressing integrin alpha1 subunit protein (INTalpha1) was examined in adult mouse tissues of not only the central nervous system, but also the sympathetic ganglia, and the adrenal gland by immunohistochemistry and immunoelectron microscopy. INTalpha1-positive neurons were observed in most tissues examined, and most of them were found to coexpress tyrosine hydroxylase (TH) except for Purkinje cells and hippocampal neurons. Expression of INTalpha1 was also observed in the malpositioned cortical neurons in reeler mutants, and appeared not to be affected by the aberrant cell migration of the reeler cortical neurons. In situ hybridization showed that the expression of INTalpha1 mRNA was correlated with synthesis of the INTalpha1 protein in each case, and this finding indicated that expression of the protein was controlled by transcriptional regulation of the INTalpha1 gene.

Adrenergic nerve smooth endoplasmic reticulum calcium buffering declines with age.

Calcium buffering capacity declines with age in sympathetic nerves of rat tail artery. To test whether smooth endoplasmic reticulum (SER) calcium buffering declines with age, effects of two SER calcium-ATPase inhibitors on norepinephrine release and intracellular calcium were determined. Thapsigargin or cyclopiazonic acid caused a significant increase in stimulation-evoked norepinephrine release from 6 month tail arteries with much less effect in 20 months. In isolated superior cervical ganglion cells, the rate of rise of calcium with K+-depolarization increased only in young cells with either cyclopiazonic acid or thapsigargin, with no effect in the old. In young cells, cyclopiazonic acid significantly influenced time to peak, rate of decline, and time to basal of K+-evoked calcium transients, but had no effect in old cells. Thapsigargin caused a significant increase in rate of decline in young, but not old, cells. These differential effects suggest an age-related decline in function of SER calcium buffering mechanisms in the sympathetic nervous system causing older nerves to become more reliant on mitochondria to buffer calcium.

Melanotic schwannoma of the sympathetic ganglia: a histologic, immunohistochemical and ultrastructural study.

We describe the case of a 46-year-old male patient who presented with pain in the left thigh, often accompanied by lumbar pain. These symptoms were sustained by a neoplasm, which was located in the sympathetic ganglia, at the level of the 3rd left lumbar spinal root and which was completely excised. Immunohistochemical positivity for S100, HMB45, and NSE antibodies suggested that the lesion was a melanotic schwannoma (MS), with both schwannian and melanocytic differentiations, the latter containing melanosomes at ultrastructural examination. Non-recurrence after 16 months of follow-up further supports our diagnosis of MS.

Synaptic organization of amphibian sympathetic ganglia.

The synaptic organization of the amphibian sympathetic ganglia was studied, especially in the last two abdominal paravertebral ganglia of the frog. These ganglia appear to form a monosynaptic relay, not containing interneurons. They consist of two systems working in parallel: the principal neurons, by far the most numerous, and a small number of chromaffin (i.e., SIF) cells, usually arranged in clusters. Each principal neuron is innervated by a preganglionic branch forming a set of cholinergic synapses which exhibit classical ultrastructure. The only peculiarity is the presence of a subsynaptic apparatus in a variable percentage of synaptic complexes. Electrophysiological studies have demonstrated that synaptic transmission is due to ACh release and involves several postsynaptic potentials. Moreover, the principal neurons are of two types, B and C, whose preganglionic axons and their own axons have different conduction velocities. C neurons tend to be small in diameter, and B neurons are larger, but the size distribution of the two populations overlaps. More recently, it was demonstrated that these two neuronal systems have different immunocytochemical features. The C preganglionic fibers contain an LHRH-like peptide, which is responsible for late synaptic events. The B preganglionic fibers contain CGRP, whose role has not yet been established. The principal neurons all contain adrenaline, but neuropeptide Y is also present in C neurons and could be a second transmitter at peripheral junctions. SP-containing fibers also pass through the ganglia, but give rise to intraganglionic synapses only rarely, except in the celiac plexus. Galanin can coexist with neuropeptide Y in certain C neurons. Numerous principal neurons are immunoreactive for VIP. Chromaffin cells contain noradrenaline and metenkephalin, and some contain SP or LHRH; they are endocrine cells controlled by preganglionic fibers and can have a modulatory effect on principal neurons endowed with appropriate receptors. The accessibility of frog abdominal ganglia and the anatomical separation of B and C preganglionic fiber pathways provide interesting systems in which to carry out experimentation on the stability and specificity of synaptic contacts. After postganglionic axotomy, the majority of synapses disappear by disruption of synaptic contacts. There is a certain discrepancy between the recovery of synaptic transmission and the reappearance of morphologically identifiable synapses, suggesting that a certain amount of transmission is possible at contacts devoid of synaptic complexes. The selective deafferentation of B or C neurons showed that the subsynaptic apparati are mainly found at B neuron synapses. The course of reinnervation following selective deafferentation reveals the existence of different specificities at B and C synapses: C neurons are easily reinnervated by B preganglionic fibers, whereas C fibers appear fairly ineffective at reinnervating B neurons, even after a long interval. Attempts were made to reinnervate ganglionic neurons with somatic motor nerve fibers. Reinnervation was achieved only rarely, and it is concluded that the ganglionic synapses in the frog have a higher specificity and lower plasticity than in mammals.

Nitric oxide synthase-containing neurons in rat parasympathetic, sympathetic and sensory ganglia: a comparative study.

In rats, the distribution of nerve structures staining for NADPH-diaphorase, and showing immunoreactivities for nitric oxide synthase (NOS), tyrosine hydroxylase and various neuropeptides was studied in sensory ganglia (dorsal root, nodose and trigeminal ganglia), in sympathetic ganglia (superior cervical, stellate, coeliac-superior and inferior mesenteric ganglia), parasympathetic ganglia (sphenopalatine, submandibular, sublingual and otic ganglia), and in the mixed parasympathetic/sympathetic ganglia (major pelvic ganglia). The coincidence of neuronal cell bodies with strong NOS-immunoreactivity and strong NADPH diaphorase reactivity was almost total. The relative proportions of NOS-immunoreactive nerve cell bodies were largest in parasympathetic ganglia and major pelvic ganglia followed by sensory ganglia. In sympathetic ganglia no NOS-immunoreactive neuronal cell bodies could be detected. In parasympathetic and major pelvic ganglia, there was a very significant neuronal co-localization of immunoreactivities for NOS and vasoactive intestinal polypeptide (VIP). This was almost total in major pelvic ganglia, in which NOS-/VIP-immunoreactive nerve cell bodies were separate from sympathetic (tyrosine hydroxylase-/neuropeptide Y-immunoreactive), suggesting that NOS-/VIP-immuno-reactive neurons might also be parasympathetic.

Bone marrow-derived elements in the peripheral nervous system. An immunohistochemical and ultrastructural investigation in chimeric rats.

BACKGROUND: Currently available studies on the peripheral nervous system (PNS) give little information on the presence, distribution, turnover and function of bone marrow-derived cells such as monocytes, macrophages, and dendritic cells. To address such issues, the present investigation of PNS tissues from bone marrow transplanted chimeras was performed. EXPERIMENTAL DESIGN: Inbred DA rats were lethally irradiated and transplanted with (Lewis x DA)F1 bone marrow carrying the non-DA major histocompatibility antigens from Lewis rats. The anti-RT-1A antibody (anti-Lewis MHC class I), I1-69, and the macrophage markers, Ed2 and Ox42 were used to visualize immunohistochemically donor bone marrow-derived cells and resident macrophages of sensory and autonomic ganglia as well as in peripheral nerves. RESULTS: In the ganglia, up to 80% and within peripheral nerves, up to 60% of macrophages were replaced by donor cells within 3 months of established chimerism. Ultrastructurally these cells were located: (a) between the perineurial sheaths, (b) in a perivascular position, or (c) freely dispersed within the endoneurium but outside the basal lamina of Schwann cells and ganglion cells. On the rare occasions where myelin and axonal pathology was noted, or during central chromatolysis of ganglion cells, donor marrow-derived cells became positioned under the basal lamina and incorporated tissue debris. CONCLUSIONS: These data suggest a rapid and significant turnover of bone marrow-derived cells within the PNS. Our observations are relevant to the understanding of the pathogenesis of reactive, immunologic, and HIV-associated processes within the PNS.

Light- and electron-microscopic study of synaptic connections in the paracervical ganglion of the female rat: special reference to calcitonin gene-related peptide-, galanin- and tachykinin (substance P and neurokinin A)-immunoreactive nerve fibers and terminals.

Nerve fibers and varicosities in the pelvic paracervical ganglia (PG) are immunoreactive for the neuropeptides calcitonin gene-related peptide, galanin, and the tachykinins substance P and neurokinin A. Many of these fibers and varicosities are capsaicin-sensitive, originate in dorsal root ganglia and, thus, are considered to be primary afferent fibers. Numerous immunoreactive varicosities are pericellular to principal neurons in the PG. The present study examines the ultrastructure of calcitonin gene-related peptide-, galanin-, substance P-, and neurokinin A-immunoreactive nerve fibers and varicosities in the ganglia to determine their relationships to principal neurons and their synaptic connectivity. Paracervical ganglia of female rats were processed for light-microscopic immunohistochemistry using antisera against synapsin I, as a nerve terminal marker, and microtubule-associated protein-2 to define soma and dendrites. The rationale for performing this co-immunohistochemical analysis was to reveal the relationship between nerve endings and principal neurons. Synapsin I endings were predominantly axosomatic with fewer being axodendritic. Other ganglia were processed for electron-microscopic immunohistochemistry using both standard immunogold and peroxidase-anti-peroxidase procedures. Unmyelinated fibers and varicosities immunoreactive for calcitonin gene-related peptide, galanin, and the tachykinins were routinely observed in the interstitium between neuron somas. Numerous immunoreactive axon profiles were present in small groups that were ensheathed by Schwann cells. Immunoreactive fibers and varicosities were also observed within the satellite-cell sheath of the neuron soma and often intimately associated with the membrane of the soma, somal protrusions, or with the proximal part of a dendrite. Membrane specializations, indicative of synaptic contacts, between the fibers and the principal neurons were observed. It is suggested that these peptide-immunoreactive sensory fibers and varicosities are involved in regulation of activity in the PG.

Subpopulations of neurons in the guinea-pig inferior mesenteric ganglia distinguished by the differential distribution of neurofilament triplet epitopes.

The distribution of the neurofilament protein triplet was examined in neurochemically identified subpopulations of neurons in the guinea-pig inferior mesenteric ganglion. A majority of the catecholamine-containing nerve cell bodies also contained the neurofilament protein triplet. However, a major proportion of the noradrenergic, neuropeptide Y-immunoreactive neurons did not contain neurofilament protein triplet immunoreactivity. Furthermore, a specific subpopulation of neurons that lacked catecholamines and were associated with the hypogastric nerve could be distinguished by the unusual feature of cell body content of post-translationally modified neurofilament protein triplet epitopes. These studies indicate that neurons in the inferior mesenteric ganglia can be distinguished by the presence of specific neurofilament protein triplet epitopes, and thus this class of intermediate filament proteins may confer specific properties to the neurons in which it is contained.

Chromaffinity, uranaffinity and argentaffinity of small granule-containing (SGC) cells in rat superior cervical ganglia.

A systemic examination on the small granule-containing (SGC) cells in rat superior cervical ganglia was conducted by conventional and cytochemical electron microscopy including chromaffin, argentaffin and uranaffin reactions. According to the fine structure of dense cored vesicles (DCVs) in the cytoplasm, three types of small granule-containing (SGC) cells were revealed--Type I: 90-160 nm vesicles with cores of moderate or low electron density; Type II: 130-330 nm vesicles, polymorphic with highly electron dense cores; Type III: elongated vesicles (170 nm x 60 nm) with cores of moderate to low electron density. The majority of SGC cells were the Type I cells (78%) and Type II and III cells made up 13% and 9% of SGC cell population, respectively. Cytochemical results demonstrated that only the Type II cells displayed a positive chromaffin reaction and all three types of SGC cells showed argentaffinity and uranaffinity. The present study is the first to demonstrate the argentaffin reaction at ultrastructural level in SGC cells of sympathetic ganglia. Based on the results of the present study we also concluded that (1) the DCVs of Type II SGC cells contained noradrenaline and (2) biogenic amines and nucleotides (ATPs) coexisted in the DCVs of all three types of SGC cells.

[Effect of chronic pathology of the upper cervical sympathetic ganglion on the cerebral cortex (experimental study)]. / O vozdeistvii khronicheskoi patologii verkhnego sheinogo simpaticheskogo gangliia na koru mozga (éksperimental'noe issledovanie)]

A study was made of the character of disorders of glycogen metabolism and dynamics of the glycogen synthetic properties of sensorimotor cortical neurons at different stages of dystrophic processes under chronic irritation of the anterior cervical ganglion. The authors demonstrate the local glycogen synthesis in synapse ultrastructures, which is of paramount importance for local homeostasis, ensuring high plasticity and dynamism of cortical synapses in information transmission. Decimetric radiotherapy revealed that the sclerosed sympathetic ganglion exerts a permanent tonic effect on the regulation of intracerebral vessels. It may be assumed that control of sympathetic fibers from the cervical ganglion is aimed to a definite measure at specialized regulation of energy brain supply.

Iron-enriched oligodendrocytes: a reexamination of their spatial distribution.

Previous histochemical studies of iron in the brain demonstrated iron enrichment in oligodendrocytes, but the iron-enriched oligodendrocytes had a spatially restricted distribution that excluded major white matter tracts. In this study we used techniques designed to permeabilize tissue, combined with iron histochemistry, and we observed iron-enriched oligodendrocytes in regions previously thought to lack such cells. Our data suggest that most, if not all, oligodendrocytes are enriched in iron. We suggest that iron functions in the formation and/or maintenance of the myelin sheet and may play a role in the pathology of myelin diseases.

Distinct and different effects of the oncogenes v-myc and v-src on avian sympathetic neurons: retroviral transfer of v-myc stimulates neuronal proliferation whereas v-src transfer enhances neuronal differentiation.

Immature avian sympathetic neurons are able to proliferate in culture for a limited number of divisions albeit expressing several neuron-specific properties. The effect of avian retroviral transfer of oncogenes on proliferation and differentiation of sympathetic neurons was investigated. Primary cultures of 6-d-old quail sympathetic ganglia, consisting of 90% neuronal cells, were infected by Myelocytomatosis virus (MC29), which contains the oncogene v-myc, and by the v-src-containing Rous sarcoma virus (RSV). RSV infection, in contrast to findings in other cellular systems, resulted in a reduction of neuronal proliferation as determined by 3H-thymidine incorporation (50% of control 4 d after infection) and in increased morphological differentiation. This is reflected by increased neurite production, cell size, and expression of neurofilament protein. In addition, RSV-infected neurons, unlike uninfected cells, are able to survive in culture for time periods up to 14 d in the absence of added neurotrophic factors. In contrast, retroviral transfer of v-myc stimulated the proliferation of immature sympathetic neurons preserving many properties of uninfected cells. The neuron-specific cell surface antigen Q211 and the adrenergic marker enzyme tyrosine hydroxylase were maintained in MC29-infected cells and in the presence of chick embryo extract the cells could be propagated over several weeks and five passages. Within 7 d after infection, the number of Q211-positive neurons increased approximately 100-fold. These data demonstrate distinct and different effects of v-src and v-myc-containing retroviruses on proliferation and differentiation of sympathetic neurons: v-src transfer results in increased differentiation, whereas v-myc transfer maintains an immature status reflected by proliferation, immature morphology, and complex growth requirements. The possibility of expanding immature neuronal populations by transfer of v-myc will be of considerable importance for the molecular analysis of neuronal proliferation and differentiation.

Neuroaxonal dystrophy in aging human sympathetic ganglia.

Autonomic dysfunction is an increasingly recognized problem in aging animals and man. The pathologic changes that produce autonomic dysfunction in human aging are largely unknown; however, in experimental animal models specific pathologic changes have been found in selected sympathetic ganglia. To address whether similar neuropathologic changes occur in aging humans, the authors have examined paravertebral and prevertebral sympathetic ganglia from a series of 56 adult autopsied nondiabetic patients. They found significant, specific, age-related neuropathologic lesions in the prevertebral sympathetic superior mesenteric ganglia of autopsied patients. Markedly swollen dystrophic preterminal axons compressed or displaced the perikarya of principal sympathetic neurons. Ultrastructurally, these swollen presynaptic axons contained abundant disoriented neurofilaments surrounded by peripherally marginated dense core vesicles. Immunohistochemical studies demonstrated that dystrophic axons contained tyrosine hydroxylase and neuropeptide tyrosine (NPY)-like immunoreactivity but not other neuropeptides (VIP, substance P, gastrin-releasing peptide [GRP]/bombesin, met-enkephalin). Similar to the animal models of aging, lesions were much more frequent in the prevertebral superior mesenteric ganglia than in the paravertebral superior cervical ganglia. These studies demonstrate anatomic, peptidergic, and pathologic specificity in the aging human nervous system similar in many respects to that which the authors have described in experimental animal models. Neuroaxonal dystrophy in the sympathetic nervous system may underlie poorly understood alterations in clinical autonomic nervous system function that develop with age.