Serotonin-containing Nerve Fibers Research Articles

Neurotrophic immunophilin ligands stimulate structural and functional recovery in neurodegenerative animal models.

Although immunosuppressant immunophilin ligands promote neurite outgrowth in vitro, their neurotrophic activities are clearly independent of their immunosuppressive activity. In the present report, a novel nonimmunosuppressive immunophilin ligand, GPI-1046 (3-(3-pyridyl)-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate+ ++) is described. In vitro, GPI-1046 bound to FK506 binding protein-12 and elicited neurite outgrowth from sensory neuronal cultures with picomolar potency with maximal effects comparable to nerve growth factor. In vivo, GPI-1046 stimulated the regeneration of lesioned sciatic nerve axons and myelin levels. In the central nervous system, GPI-1046 promoted protection and/or sprouting of serotonin-containing nerve fibers in somatosensory cortex following parachloroamphetamine treatment. GPI-1046 also induced regenerative sprouting from spared nigrostriatal dopaminergic neurons following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice or 6-hydroxydopamine (6-OHDA) toxicity in rats. The rotational abnormality in 6-OHDA treated rats was alleviated by GPI-1046. These neurotrophic actions in multiple models suggest therapeutic utility for GPI-1046 in neurodegenerative diseases.

Light and electron microscopic immunohistochemical studies of serotonin nerve fibers in the substantia nigra of the rat, cat and monkey.

The distribution of serotonin-containing nerve fibers in the substantia nigra of the rat, cat and monkey was studied with a highly sensitive peroxidase-antiperoxidase immunohistochemical method. Serotonin fibers in the substantia nigra of all species consisted of fine varicose fibers and formed a fine network. In the zona compacta of all species, serotonin fibers were sparsely distributed. In the zona reticularis of the rat and cat, these fibers were densely distributed and their distributional pattern was almost uniform, while in the monkey such fibers were unevenly distributed and high and low dense areas were intermingled. In the pars lateralis of all species, serotonin fibers were diffusely distributed, and the distributional density was much higher in the cat and monkey than in the rat. Immunoelectron-microscopic studies further revealed that a majority of the labeled varicosities in the rat substantia nigra were in close apposition to peridendritic axon terminals and were also free in the neuropil; occasionally they exhibited symmetrical synapses of "en passant" type with non-immunoreactive dendrites or somata. Our results support a functional significance of serotonergic regulation of the substantia nigra in mammals.

Serotonin-containing nerve fibers in the rat spinal cord: electron microscopic immunohistochemistry.

The ultrastructure of the serotonin (5HT) system in the spinal cord of rats was studied by an immunohistochemical peroxidase-antiperoxidase (PAP) method. Under the light microscope, 5HT immunoreactive staining was observed as brown-colored dots in the anterior horn, lateral horn, posterior horn and pericentral canal region. These positively staining dots were probably indicative of 5HT immunoreactive varicosities and nerve terminals. At the ultrastructural level, 5HT immunoreactive nerve fibers appeared as darkly stained varicosities with PAP positive large electron dense vesicles (80-100 nm), as well as small clear vesicles (30-40 nm) finely coated with PAP immunoreactive products. In the anterior horn, some of the 5HT immunoreactive structures were clearly nerve terminals forming asymmetric synaptic contact with soma or dendrites of the anterior horn cells. In the lateral horn, posterior horn and pericentral canal region, however, only 5HT positive varicosities were detected.

Immunohistochemical demonstration of serotonin-containing nerve fibers in the substantia nigra

Immunohistochemical demonstration of serotonin-containing nerve fibers in the substantia nigra

Distribution of serotonin in the brain stem and spinal cord of the lizard Varanus exanthematicus: An immunohistochemical study

The distribution of serotonin-containing nerve cell bodies, fibers and terminals in the lizard Varanus exanthematicus was studied with the indirect immunofluorescence technique, using antibodies to serotonin. Most of the serotonin-containing cell bodies were found in the midline, in both of the raphe nuclei, i.e. the nuclei raphes superior and inferior. A considerable number of more laterally shifted serotonergic neurons was found particularly at three levels of the brain stem, viz. in the caudal mesencephalic tegmentum, at the isthmic level, and over a long distance in the medulla oblongata. These laterally situated serotonin-positive neurons were partly found within the confines of the substantia nigra, the nucleus reticularis superior and the lateral part of the nucleus reticularis medius and ventrolateral part of the nucleus reticularis inferior, respectively. No serotonergic cell bodies were found in the spinal cord. In the brain stem a dense serotonergic innervation was observed in all of the motor nuclei of the cranial nerves, in two layers of the tectum mesencephali, in the nucleus interpeduncularis pars ventralis, the nucleus profundus mesencephali pars rostralis, the periventricular grey, the nucleus parabrachialis, the vestibular nuclear complex, the nucleus descendens nervi trigemini, the nucleus raphes inferior, and parts of the nucleus tractus solitarii. Descending serotonergic pathways could be traced into the spinal cord via the dorsolateral, ventral and ventromedial funiculi, and were found to innervate mainly three parts of the spinal grey throughout the spinal cord, i.e. the dorsal part of the dorsal horn, the motoneuron area in the ventral horn, and the intermediate zone just lateral to the central canal. The results obtained in the present study suggest a close resemblance of the organization of the serotonergic system in reptiles and mammals, especially as to the serotonergic innervation of the spinal cord.

Immunohistochemical demonstration of serotonin-containing nerve fibers in the corpus striatum of the rat, cat and monkey

The discovery of glucagon biosynthesis and receptors within mammalian brain has led one to suspect a neurotransmitter role for glucagon. In order to address this hypothesis in birds, we investigated the existence of glucagon receptors in duck brain by radioligand binding on fresh tissue sections and radioautography. Specific high-affinity [125I]glucagon binding sites similar to those in the liver were demonstrated in the avian brain. Mapping of these putative glucagon receptors revealed a discrete distributional pattern. Most of the [125I]glucagon binding capacity in duck brain is concentrated within the telencephalon, mainly in components of motor and limbic systems. Specific labeling densities were associated with avian equivalents of the mammalian pyramidal system (hyperstriatum accessorium; archistriatum intermedium and tractus occipitomesencephalicus) and extrapyramidal system (paleostriatum augmentatum, paleostriatum primitivum and lobus parolfactorius), as well as several limbic structures (hippocampal formation, nucleus taeniae and the caudal part of the archistriatum). Few glucagon-reactive foci were detected in the diencephalon (the nucleus dorsomedialis of hypothalamus, the two circumventricular organs, organum vasculosum of the lamina terminalis and median eminence and the nucleus habenularis medialis). These findings suggest that glucagon might be involved in the central control of somatic motricity and basic behaviors and point therefore to glucagon as a new neuroactive messenger in avian brain. The extensive difference between the distribution of glucagon binding sites observed in duck brain and that previously reported in rat brain suggests that glucagon does not subserve the same physiological role(s) in avian and mammalian brains.

Immunohistochemical demonstration of serotonin-containing nerve fibers in the corpus striatum of the rat, cat and monkey

Immunohistochemical demonstration of serotonin-containing nerve fibers in the corpus striatum of the rat, cat and monkey

Immunohistochemical demonstration of serotonin-containing nerve fibers in the hypothalamus of the monkey, Macaca fuscata.

The distributional pattern of serotonin-containing nerve fibers in the hypothalamus of the monkey (Macaca fuscata) was analyzed with the use of the peroxidase-antiperoxidase method in conjunction with a highly sensitive and specific anti-serotonin serum. The highest concentrations of serotonin-immunoreactive varicose fibers were found in the nucleus praeopticus medialis, nucleus ventromedialis hypothalami, and the complex of mammillary nuclei (nucleus praemamillaris, supramamillaris, mamillaris medialis et lateralis). However, the nucleus suprachiasmaticus, where numerous serotoninergic fibers have been reported to occur in the rat, appeared to be almost devoid of these fibers. The infundibular stalk and the intermediate and posterior lobes of the pituitary contained considerable numbers of immunoreactive fibers. The present study provides a morphological basis for possible clarification of the influence of serotoninergic projections on various neuroendocrine mechanisms in primates. Furthermore, an attempt was made to clarify the differences and similarities concerning the distributional patterns of serotoninergic nerve fibers within the monkey hypothalamus in contrast to the rat hypothalamus.

On the origin of the serotonergic input to the intermediate lobe of the rat pituitary

Serotonin-containing nerve fibers have been visualized immunocytochemically in the intermediate lobe of the rat pituitary. A 50% depletion of the serotonin level in the intermediate lobe was obtained in our previous experiment in rats with pituitary stalk transection, which may represent the total neuronally derived serotonin there. In the present studies we have attempted to determine the source of these fibers by examining the effect of hypothalamic and midbrain lesions or fiber transections on serotonin levels and serotonin-containing neuronal elements. Complete hypothalamic deafferentation resulted in a significant reduction of immunostained fibers in the intermediate lobe. A 27% fall in the serotonin content (measured by HPLC and electrochemical detection) and a significant disappearance of immunostained fibers were observed after transecting the ascending fibers from the raphe nuclei towards the hypothalamus. The transection combined with the lesioning of the hypothalamic dorsomedial nuclei resulted in a 50% decrease of serotonin level in the intermediate lobe. The present data therefore suggest that serotonin fibers in the intermediate lobe may originate from cells both in the midbrain raphe and hypothalamic dorsomedial nuclei.

Serotoninergic fibers in dorsal roots of the spinal cord

In the lumbar segment of the spinal cord, serotonin-containing nerve fibers are shown to connect the descending serotoninergic pathway of the intermediolateral column with the ipsilateral dorsal root. This may suggest that efferent serotoninergic fibers, originating from brainstem raphe nuclei, leave the spinal cord via the dorsal roots. However, when tryptophan pretreatment is employed in addition to a monoamine oxidase inhibitor, a limited number of yellow-fluorescing neurons can at times also be visualized in the dorsal ganglia. These could be the cell bodies of origin of at least some of the above-mentioned serotonin-containing nerve fibers, which would then have, at least in part, an afferent, sensory function. At present, therefore, the origin and function of this newly discovered serotoninergic pathway remains to be clarified.

Immunohistochemical study on the localization of serotonin fibers and terminals in the spinal cord of the monkey (Macaca fuscata).

A modified procedure of PAP-immunohistochemistry with the use of a rabbit antiserum against serotonin was applied to investigate the pattern of serotonin-containing nerve fibers in the spinal cord of the monkey, Macaca fuscata. The majority of descending serotonin fibers in the white matter is located immediately below the pia mater in the ventrolateral funiculi. Lamina I and the outer zone of lamina II are supplied with numerous serotonin fibers. In the intermediate gray, two prominent bundles composed of longitudinal fibers, i.e., lateral and medial longitudinal serotonin bundles, were recognized at the lateral column and in the vicinity of the central canal, respectively. The motoneurons of the anterior horn are encompassed by fine networks of serotonin fibers and terminals. The results obtained from studies with the monkey spinal cord closely resemble those characteristic of the dog spinal cord as presented in a previous paper, except for portions of the lumbar level. In segments L3-L4, intercalated cell groups between the medial and lateral motor nuclei receive particularly rich inputs of serotonin fibers in the same manner as the neurons of the nucleus intermediolateralis. This peculiar finding may suggest the presence of a specialized nucleus in the anterior column of the simian and also human spinal cord.