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Biomedical subjects

D L Felten

Publications and source records attributed to D L Felten.

At least 145 records · Page 8Linked to original sources

The raphe nuclei of the rabbit brain stem.

The raphe nuclei of the rabbit brain stem were found in the midline and adjacent reticular formation of the medulla, pons, and mesencephalon. Nuclei raphe obscurus, pallidus, and magnus were located in the medulla. Nucleus raphe pontis and the caudal portion of nuclei raphe dorsalis and centralis superior were present in the pons. The rostral portion of nuclei raphe dorsalis and centralis superior, and nuclei linearis caudalis and intermedius were present in the msencephalon. Wings of neurons extended from the midline clusters of raphe neurons into the adjacent reticular formation. These wings of neurons contained serotonergic perikarya which were cytoarchitecturally indistinguishable from the midline neurons. A detailed localization of these nuclei is presented in atlas form. These raphe nuclei contained heterogeneous populations of neurons which varied in the size, shape and density of the cell bodies. In addition, the dendritic branching, specific orientation of dendrites, and appearance of spines were distinct for each of the raphe nuclei. Individual raphe nuclei often contained several subpopulations of neurons characterized by unique spatial configuration and orientation. The main morphological similarities of the raphe nuclei are location in or adjacent to the midline, the presence of serotonergic cell bodies in all raphe nuclei except the linear nuclei, and heterogeneous cell populations.

Afferent Pathways↗

A raphe dendrite bundle in the rabbit medulla.

A Golgi-Cox, histofluorescence, and electron microscopic examination of the serotonergic raphe nuclei of the rabbit medulla has revealed a large, vertically-oriented midline dendrite bundle extending from the floor of the fourth ventricle to the ventral boundary of nucleus raphe pallidus. The bundle was confined to the medulla, and averaged 150-200 micrometer in width in the adult. This dendrite bundle received contributions from four major sources: (1) Dendrites of midline and paramedian neurons of nucleus raphe obscurus; (2) Dendrites of midline and paramedian neurons of nucleus raphe pallidus; (3) Shafts from tanycytes located on the midline floor of the fourth ventricle; and (4) Dendrites from neurons of the medullary reticular formation. Perikarya and dendrites of serotonergic raphe neurons frequently abutted tanycyte shafts, midline bhood vessels, and perikarya and dendrites of other raphe neurons. The tanycyte shafts extended from the floor of the fourth ventricle into the bundle, and often ran the entire length of the bundle, where they intertwined themselves among neurons and dendrites of the medullary raphe nuclei. This study suggests that neurons of the medullary raphe may be influenced by communication channels including dendro-dendritic contacts within the midline bundle, fourth ventricular cerebrospinal fluid-borne influences through tanycyte shafts, blood-borne influences through the direct neuronal-vascular relationship in the raphe, and traditionally described axonal contacts impinging upon raphe neurons. We suggest that the raphe neurons might act as both neurons and endocrine-neural transducer cells.

Animals↗

Neuronal-vascular relationships in the raphe nuclei, locus coeruleus, and substantia nigra in primates.

A fluorescence histochemical and electron microscopic study of the monoaminergic cell groups in the squirrel monkey and Rhesus monkey brains has revealed the direct apposition of blood vessels to perikarya and dendrites of monoaminergic neurons. Capillaries and small arterioles or venules, ranging from 8-50 microns in diameter, showed perikarya and dendrites abutting the basement membrane without evidence of glial interposition. This neuronal-vascular relationship was present in 20% to 30% of the small vessels in the serotonergic nuclei raphe dorsalis and centralis superior and in the noradrenergic locus coeruleus. Such contacts were clearly present but observed less frequently in the dopaminergic substantia nigra pars compacta and in the serotonergic nuclei raphe obscurus, pallidus, magnus, and pontis. We postulate that monoamine-containing neurons apposed to blood vessels in certain regions of the brain may be influenced directly by hormones or other substances in blood.

Animals↗

HPLC determination of biogenic amines in discrete brain areas in food deprived rats.

Norepinephrine (NE), dopamine (DA), 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) levels in the lateral hypothalamus (LH), ventromedial hypothalamus (VMH), median raphe (MR) and dorsal raphe (DR) were determined in nondeprived and 48 hr food deprived rats. Simultaneous determination of these compounds was accomplished by means of high performance liquid chromatography (HPLC) with electrochemical detection. When compared with controls, food deprived animals showed significant increases in 5-HT and 5-HIAA levels in the raphe nuclei, significant increases in 5-HIAA in the LH, but no changes in either 5-HT or 5-HIAA levels in the VMH. No changes in catecholamine levels were found in any of the brain areas studied. These results show that indoles in the raphe nuclei, as well as in the LH, are affected by food deprivation. The lack of change in indole levels in the VMH indicates that specific nuclei within the hypothalamus are differentially affected by food deprivation.

Animals↗

Cytoarchitecture of the supraoptic nucleus. A Golgi study.

A Golgi-Cox study of the supraoptic nucleus of the adult rabbit has revealed the presence of three major cell types: (1) large multipolar neurons; (2) large bipolar neurons, and (3) small interneurons. The multipolar and bipolar neurons demonstrated regional variation in the rostral and caudal aspects of this nucleus, while the interneurons appeared identical throughout the nucleus. This study provides detailed cytoarchitectural descriptions of the magnocellular neurosecretory cells in the supraoptic nucleus and establishes the presence of an interneuronal cell population through which incoming afferent messages could influence the neurosecretory neurons.

Animals↗

Monoamine distribution in primate brain. III. Catecholamine-containing varicosities in the hypothalamus of Macaca mulatta.

The histochemical fluorescence technique of Falck and Hillarp was used to examine the distribution of catecholamine-containing varicostities within the hypothalamus of the rhesus monkey (Macaca mulatta). Varicosities were seen in heaviest concentrations within the periventricular area and the following nuclei: lateral and madial preoptic, supraoptic, paraventricular, arcuate and dorsomedial. Patterns observed presented striking similarities and dissimilarities to catecholamine distribution reported in the rat and car. Catecholaminergic perikarya were not observed routinely.

Animals↗

A histochemical investigation of catecholamines in spinal cord injury.

The catecholamine hypothesis of progressive spinal cord necrosis following mechanical trauma was investigated with the histofluorometric method. Forty-four adult mongrel dog were examined as control, L1 crush-injured, and crush-injured with prior T1 total transection groups. In crush injured dogs, catecholamines were present in a 1 cm length of white matter at the crush site, with the greatest accumulation in the deep lateral and ventral funiculi. Gray matter fluorescence was not enhanced. Prior transection did not abolish the intense accumulation of catecholamines at the site of the cord injury. We propose that the catecholamines accumulating at the cord injured site are not central in origin, but represent an uptake mechanism into white matter as a reflection of cord microperfusion.

Animals↗

Catecholamine neurons in the squirrel monkey hypothalamus.

Catecholamine neurons were found in the periventricular nucleus, arcuate nucleus, and a region around the mammillothalamic tract in the hypothalamus of the squirrel monkey. These neurons did not fluoresce in control or monoamine-oxidase-inhibited animals, and exhibited fluorescence only after intraventricular injections of alpha-methyl-norepinephrine. Dense accumulations of catecholamine varicosities appeared in the periventricular nucleus, external contact zone of the median eminence, and perivascular region of the median eminence; the arcuate nucleus contained no more than a moderate density of catecholamine varicosities. The median eminence fluorescence had a regional character, with greatest intensity in the caudal portion.

Animals↗

Glycogen accumulation in tibial nerves of experimentally diabetic and aging control rats.

Tibial nerves of streptozotocin-diabetic, alloxan-diabetic, and age-matched control rats were examined at 2 weeks and 2, 4, 8, and 12 months following the induction of diabetes. Glycogen-like granules accumulated within perineurial and Schwann cells of only the diabetic animals. This accumulation may reflect a metabolic abnormality in these cells which could account for the reduced conduction velocities seen in the peripheral nerves of these same diabetic rats (Moore et al. 1980a). Glycogen-like granules were also present and increased with age in myelinated axons of both diabetic and control rats. Quantitative data suggest that axonal accumulation of glycogen-like granules is related to aging or injury related phenomena to which diabetic axons may be more susceptible.

Aging↗

Substance P innervation of the rat thymus.

Immunohistochemistry for substance P (SP) in the rat thymus revealed fine varicose neural profiles in specific regions of the thymus. Thymic SP innervation was abundant within the capsule and interlobular septa. The majority of SP+ nerve fibers within the septa were free of vascular association, although some fibers were associated with the vasculature deep within the septa. SP+ nerve fibers entered the thymic cortex from the septa and distributed among cortical thymocytes and mast cells. Along the corticomedullary junction, SP+ nerve fibers were found in association with the vasculature. The medullary region of the thymus received only a sparse innervation of SP+ fibers. In addition, SP+ nerve fibers coursed adjacent to OX-8+ cells and mast cells in the extrathymic connective tissue surrounding the thymus. The present study provides evidence that SP is present in nerve fibers in the thymus, and may be available to interact with thymocytes, mast cells, and other cells in the thymus, and affect their development and function.

Animals↗

Decreased sympathetic innervation of spleen in aged Fischer 344 rats.

Splenic noradrenergic innervation in young adult and aged Fischer 344 rats was examined using fluorescence histochemistry for catecholamines and high performance liquid chromatography with electrochemical detection (LCEC) for the quantitation of norepinephrine (NE). In young adult rats, abundant noradrenergic plexuses followed the vasculature and trabeculae into splenic white pulp. In aged rats, noradrenergic innervation was reduced in density and in overall intensity of fluorescence, and splenic NE levels were significantly lower. The relationship between diminished noradrenergic innervation and diminished immune responsiveness in aging mammals, while not clear on a causal level, is presented as a hypothesis for further testing.

Aging↗

Chronic dietary pergolide preserves nigrostriatal neuronal integrity in aged-Fischer-344 rats.

Pergolide, a potent D2 presynaptic agonist with postsynaptic D2 agonist activity and some D1 agonist activity was administered in the diet (0.5 mg/kg/day) of male Fischer 344 rats from age 3 to age 26 months. We hypothesized that the potent D2 presynaptic activity would reduce the baseline release of dopamine (DA) and thereby slow the formation of toxic oxidative metabolites that lead to age-related deterioration of nigrostriatal DA neurons. Pair-fed rats served as controls. We observed age-related losses of fluorescent DA cell bodies in the substantia nigra pars compacta and of fluorescent DA terminals in the striatum; chronic pergolide administration prevented these losses. Pergolide administration also prevented the age-related diminution of DA fluorescence intensity in substantia nigra cell bodies. A large decline in 3H-DA uptake with age was partially prevented by pergolide administration. We found no age-related alteration in the concentration of DA in the striatum and pergolide did not alter this concentration. Pergolide treatment resulted in only minor alterations in striatal 3H-spiperone binding and no change in dendritic arborizations of either DA substantia nigra neurons or medium spiny striatal neurons. Pergolide administration also prevented an age-related decline in circulating FSH levels. The uptake data and quantitative morphological findings suggest that pergolide administration in the diet for 2 years exerts a protective effect on age-related deterioration of DA nigrostriatal neurons. This finding was consistent with clinical reports of a subset of patients with Parkinson's disease in whom long-term efficacy of pergolide therapy is observed.

Aging↗

Catecholamines and serotonin in the caudal medulla of the rat: combined neurochemical-histofluorescence study.

The distribution of monoamine transmitters among the nuclei of the caudal medulla was determined through the combined use of the Falck-Hillarp histofluorescence method for cellular localization of catecholamines and serotonin and quantitative micropunch neurochemical assays of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) content using high performance liquid chromatography with electrochemical detection. These combined methods permit a direct correlation between neurotransmitter levels and fluorescent fiber and perikaryal profiles. Eight medullary nuclei were sampled: (1) dorsal motor nucleus of X and ventral nucleus solitarius, (2) the dorsomedial reticular formation, (3) the hypoglossal nucleus, (4) the ventromedial reticular formation, (5) the nucleus ambiguus, (6) nuclei raphe obscurus and pallidus, (7) the inferior olivary nucleus and (8) the descending (spinal) nucleus of V. Micropunched regions containing neurons which contribute projections to or receive sensory input from the vagus nerve were found to contain relatively high levels of NE, DA and 5-HT, consistent with the high density of catecholamine and 5-HT containing terminals observed in these nuclei. The dorsal motor nucleus of X and ventral nucleus solitarius contained the highest levels of NE, DA and 5-HT (218 +/- 10, 31 +/- 2 and 75 +/- 8 pmole/mg protein, respectively), whereas the lowest of these amines were found in the descending (spinal) nucleus of V (28 +/- 1, 3.6 +/- 0.8 and 32 +/- 2 pmole/mg protein, respectively). In general the distribution of catecholamines and 5-HT determined by micropunch/microchemical assay agrees well with the distribution of monoamine terminals detected by fluorescence histochemical techniques.

Animals↗

Age-associated alterations in sympathetic neural interactions with the immune system.

We have examined age-related alterations in sympathetic noradrenergic (NA) innervation in primary and secondary lymphoid organs from mouse and rat. As the thymus involuted with age, the density of NA innervation and norepinephrine (NE) concentration increased markedly. Total thymic NE was not altered significantly with age, suggesting that NA innervation is maintained as the thymus involutes. In the rat spleen, NA innervation and NE concentration were diminished with age. Enhanced antibody responses and in vitro proliferation to a T-dependent protein antigen were observed following selective destruction of NA nerve fibers with the neurotoxin 6-hydroxydopamine (6-OHDA), demonstrating that the diminished NA innervation in the aged spleen is capable of signaling the immune system. Plasticity of NA nerves in old rats was demonstrated following lesioning with 6-OHDA and in intact rats treated with L-deprenyl, a monoamine oxidase B inhibitor. These age-related alterations in NA innervation of lymphoid organs occur concurrently with age-associated changes in immune function. Understanding the functional relationship between these two physiological systems in aging will contribute to a greater understanding of sympathetic nervous system regulation of immune function.

Age Factors↗