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S Y Felten

Publications and source records attributed to S Y Felten.

At least 55 records · Page 3Linked to original sources
PubMed1990

MPTP-treated young mice but not aging mice show partial recovery of the nigrostriatal dopaminergic system by stereotaxic injection of acidic fibroblast growth factor (aFGF).

Acidic fibroblast growth factor (aFGF) is a heparin-binding polypeptide that acts as a neurotrophic factor for certain central and peripheral neurons. Acidic FGF was injected stereotaxically into the striatum of young (2-month-old) and aging (12-month-old) C57BL/6 mice that were treated 1 week before with systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP treatment (4 x 20 mg/kg, i.p. given 12 h apart) reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum and reduced dopamine (DA) concentration to 32% of the controls in young and 20% of the controls in aging mouse brain 5 weeks after administration. Although the DA concentration recovered to 43% of the controls in young mice following stereotaxic injection of aFGF 5 weeks after MPTP treatment, aging mice with such treatment did not show a significant recovery of DA concentration. Computerized image analysis of TH-IR fibers in the striatum also showed significant recovery in young mice treated with aFGF, while aging mice did not show a significant recovery. We conclude that treatment of MPTP-depleted young mice with aFGF results in partial recovery in the nigrostriatal DA system but such benefits decline with age.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Long-term effect of MPTP in the mouse brain in relation to aging: neurochemical and immunocytochemical analysis.

The long-term effect of the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central monoaminergic neurons in young (2-3 months) and aging (12 months) C57BL/6 mice has been studied using neurochemical and immunocytochemical techniques. MPTP treatment (4 x 20 mg/kg i.p. given 12 h apart) resulted in significant depletion of dopamine (DA) concentration in the striatum, substantia nigra, nucleus accumbens, and olfactory tubercle 1 week after treatment in both young and aging mice. Although a decreased DA concentration in the ventral tegmental area was not seen in young mice, aging mice did show a significant decrease. The extent of decrease of DA concentration was greater in aging mice than in young mice in all areas investigated except in dorsal striatum. The long-term effect of MPTP on DA neurons in young mice included considerable recovery of DA concentration in both nigrostriatal and mesolimbic DA systems following the initial profound depletion; such recovery was minimal in aging mice, even 3 months after MPTP treatment. In young mice treated with MPTP, no significant change of norepinephrine (NE) or serotonin (5-HT) concentration was observed in any area investigated while a significant decrease of NE and 5-HT concentration was seen in several brain areas investigated in aging mice. Immunocytochemical analysis revealed that the MPTP injection resulted in marked disappearance of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in striatum of both young and aging mice 1 week following treatment. Partial recovery of TH-IR fibers was seen 5 weeks or 3 months after MPTP treatment in young mice, while no such apparent recovery was seen in aging mice. Aging mice also showed significant decrease in the number of TH-positive cell bodies in the substantia nigra and ventral tegmental area through all periods investigated, while such a significant decrease was only seen in the substantia nigra of young mice 1 week after treatment. We conclude that aging mice are more sensitive to MPTP and show more widespread damage to the monoaminergic systems than young mice, suggesting that MPTP-treated aging mice provide a more useful model for studying anatomical and neurochemical characteristics of Parkinson's disease than young mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Limited recovery of striatal dopaminergic fibers by adrenal medullary grafts in MPTP-treated aging mice.

Systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages the dopaminergic (DA) nigrostriatal system in C57BL/6 mice. We have investigated the effect of MPTP neurotoxicity and subsequent adrenal medullary grafts into the striatum of young (2-3 months) and aging (12 months) mice. MPTP treatment (4 X 20 mg/kg ip given 3 or 12 h apart in young mice and 12 h apart in aging mice) resulted in 80-90% depletion of striatal DA and virtual disappearance of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in both young and aging mice 1 week following treatment. Only partial recovery of TH-IR fibers was seen 5 weeks after MPTP treatment in young mice, while virtually no recovery was seen in aging mice. Adrenal medullary minced pieces were grafted into the striatum of young and aging mice 1 week after MPTP treatment. In young mice, dense TH-IR fibers were observed in the striatum on the grafted side 4 weeks later, far denser than those in sham-operated striatum. Although this staining was most prominent around the grafts, many TH-IR fibers also were found in the ventral striatum close to the nucleus accumbens. No such increase in TH-IR fibers was found on the nongrafted side. DA concentration on the grafted side recovered to 45% of the control level. In aging mice receiving similar grafts, TH-IR fibers also were observed in the grafted striatum, but were less dense and more restricted around the site of the graft compared with young mice. DA concentration on the grafted side was 29% of the control level. We conclude that the MPTP-depleted nigrostriatal DA system in aging mouse brain can recover partially following adrenal medullary grafts, but the degree of recovery is more limited compared with that in young brain.

Adrenal Medulla↗
PubMed1990

Noradrenergic reinnervation of the rat spleen following chemical sympathectomy with 6-hydroxydopamine: pattern and time course of reinnervation.

The time course and pattern of reinnervation of noradrenergic (NA) sympathetic nerve fibers into the spleen following acute chemical sympathectomy with the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) was examined in young adult male Fischer 344 rats using glyoxylic acid fluorescence histochemistry and neurochemical measurement of NE. Reinnervation proceeds initially along the splenic artery as it enters the hilus (1-5 days), extends into the hilar region (5-10 days), and later proceeds into the regions distal to the hilus (21-56 days), suggestive of orderly growth from the hilar region to distal regions. In all 6-OHDA-treated spleens, the compartmentation of NA innervation was similar to that observed in saline-injected controls, but the density of NA nerve fibers in these compartments differed according to the distance from the hilus. By 56 days postlesion, regions distal to the hilar blood vessels contained fewer NA profiles than their age-matched controls, suggesting that the anatomical process of reinnervation does not restore the density of fibers in a fashion identical to that of nondenervated controls. In contrast, splenic NE concentration at 56 days postdenervation did not differ from the concentration seen in nondenervated control spleens. We suggest that functional restoration of splenic innervation may involve metabolic and receptor compensation for the lack of complete fiber regrowth into regions of white pulp distal from the hilus.

Adrenergic Fibers↗
PubMed1990

Fluorescence histochemical techniques for catecholamines as tools in neurobiology.

Formaldehyde-induced and glyoxylic-acid-induced fluorescence histochemistry permits the tissue localization of catecholamines in the central nervous system (CNS) and peripheral nervous system (PNS), and in culture. Counterstains such as ethidium bromide provide excellent background identification of specific innervated regions in both the CNS and the periphery. Use of fluorescence histochemistry with immunocytochemistry can elucidate catecholamine-peptide relationships. Gelatin-ink perfusion used with fluorescence histochemistry permits the investigation of neuro-vascular relationships and documentation of vascular and parenchymal compartmentation of innervation. Combined use of fluorescence histochemistry and retrograde tracing methods demonstrates the specific cellular sources of innervation of target regions. Micropunch neurochemical analysis provides quantitative data for correlation with fluorescence histochemistry within a target region of innervation, and microspectrofluorometric analysis provides a semi-quantitative evaluation of the amount of fluorophore within a target region or within specific subcellular compartments such as the cell body or terminals.

Animals↗
PubMed1989

Exogenous GM1 gangliosides induce partial recovery of the nigrostriatal dopaminergic system in MPTP-treated young mice but not in aging mice.

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to young (2-3 months) and aging (12 months) C57BL/6 mice (4 x 20 mg/kg, i.p., given 12 h apart) reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum, and reduced dopamine (DA) concentration to 28% of controls in young, and 16% of controls in aging mouse brain five weeks after administration. Although GM1 ganglioside treatment (30 mg/kg, i.p., daily for 5 weeks) restored striatal dopamine concentration to 74% of the control concentration in young mice, such an apparent recovery was not seen in aging brain. Immunocytochemical analysis also showed marked recovery of TH-IR fibers in the striatum of MPTP-depleted young mice treated with GM1 ganglioside while TH-IR fibers in the striatum of MPTP-depleted aging mice showed no recovery with such treatment. We conclude that treatment of MPTP-depleted young mice with GM1 ganglioside results in partial recovery in the striatal DA system, but such benefits do not extend to aging mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Parallel development of noradrenergic innervation and cellular compartmentation in the rat spleen.

By combining neurochemical measurement of norepinephrine (NE) with double-label immunocytochemistry for tyrosine hydroxylase-positive (TH+) noradrenergic nerves and specific lymphoid markers, we have examined the developmental compartmentation of noradrenergic nerves in the rat spleen. TH+ nerve fibers were present in the white pulp of the spleen at birth, among surface IgM-positive (sIgM+) B lymphocytes at the outer border of the periarteriolar lymphatic sheath (PALS), distant from the central artery. During the first 7 days, noradrenergic innervation developed rapidly, forming plexuses of nerve fibers along the central artery and its branches, among T and B lymphocytes of the PALS, and along the developing marginal sinus where ED3+ macrophages accumulate. The splenic concentration of NE (per mg wet wt.) and 3-methoxy-4-hydroxy-phenetheleneglycol (MHPG), a NE metabolite, increased rapidly during this period, suggesting that NE is available and released from these nerves. From 7-14 days, the white pulp expanded to include an inner PALS, outer PALS, marginal sinus, and marginal zone; during this period, TH+ fibers arborized principally among T lymphocytes of the inner PALS and adjacent to macrophages along the marginal sinus. By 14 days of age, NE concentration reached adult levels, although the MHPG/NE ratio (an index of NE turnover) remained higher throughout development than in adulthood. Finally, from 14-28 days, the outer PALS expanded to include follicles containing sIgM+ B lymphocytes. At the earliest stages of follicular development, a parafollicular rim of noradrenergic fibers was present, providing occasional branches which arborized within the follicle. No further changes were observed in either noradrenergic innervation or cellular compartmentation after 28 days of age. These findings suggest that noradrenergic fibers are present in developing compartments of the spleen at the earliest stages of their development, providing norepinephrine for interaction with a variety of adrenoceptor-bearing lymphoid and nonlymphoid cells.

Animals↗
PubMed1989

Sympathetic neural modulation of the immune system. I. Depression of T cell immunity in vivo and vitro following chemical sympathectomy.

Chemical sympathectomy of adult mice with 6-hydroxydopamine (6-OHDA) either prior to or following epicutaneous sensitization with the trinitrophenyl (TNP) hapten decreased the delayed hypersensitivity (DH) response to ear challenge. To determine if uptake of 6-OHDA into sympathetic nerve terminals, and their subsequent destruction, was required for suppression of DH, the catecholamine uptake blocker, desipramine, was employed to block 6-OHDA-induced sympathetic denervation. Pretreatment with desipramine prevented the depression of DH. In vivo treatment with the beta blocker, propranolol, did not alter the 6-OHDA effect, eliminating the potential contribution of released catecholamines, acting on beta-adrenoceptors, to DH reduction. Sympathectomy before sensitization also diminished hapten-specific T cell reactivity of sensitized lymph node (LN) cells, as measured in vitro by IL-2 production and CTL generation. In vivo DNA synthesis in draining LN in response to immunization was modestly decreased following 6-OHDA. Thus, sympathetic denervation appears to impair T cell activity in vivo and in vitro. Overall, these results indicate the SNS plays a role in generation of cell-mediated immunity.

Animals↗
PubMed1989

Origin of noradrenergic innervation of the spleen in rats.

Noradrenergic (NA) sympathetic innervation of the spleen was examined in young adult Sprague-Dawley rats (200-250 g) following surgical removal of the superior mesenteric-celiac ganglia (SM-CG) and/or bilateral transection of the subdiaphragmatic vagus nerve. Sham-operated and unoperated rats served as controls. NA sympathetic innervation of spleens from sham-operated and unoperated controls, and from vagotomized rats, was qualitatively similar, with fibers distributing to the capsule, trabeculae, vasculature, and parenchyma of the white pulp. Complete ganglionic extirpation resulted in almost total denervation of NA fibers in all compartments of the spleen. High-performance liquid chromatography with electrochemical detection (LCEC) for catecholamines (CA) and quantitative morphometry of the density of NA varicosities confirmed these observations. LCEC revealed a greater than 85% depletion of norepinephrine (NE) in the spleen following superior mesenteric-celiac ganglionectomy. Stereological evaluation of NA varicosities with a point counting method revealed a decline of 99% in the volume density of NA terminals that occurred uniformly in all compartments of spleens from ganglionectomized rats. In addition, stereological analysis revealed a loss of total NA varicosities (approximately 31% decrease) in spleens from sham-operated rats. This loss in volume density occurred largely due to a loss in parenchymal fibers (approximately 45% decrease). Bilateral subdiaphragmatic vagotomy blocked the effect on NA innervation produced by the surgical stress of sham operation. Retrograde tracing following injection of either fluorogold or true blue into the spleen, coupled with immunocytochemical localization of tyrosine hydroxylase (TH), demonstrated abundant fluorogold (true blue)-labeled neurons in the SM-CG; many, but not all, of these neurons also were TH-positive. These findings indicate that the SM-CG neurons supply NA innervation to the spleen, providing sympathetic innervation as the second neuron in the classical two-neuron sympathetic chain, and suggest additional non-NA innervation of the spleen as well. This study also suggests that surgical stress of sham operation may alter directly the NA innervation of the spleen, possibly by inducing temporary retraction of NA fibers of the parenchymal compartment, which is likely to reduce the availability of NE for interaction with cells of the immune system that possess adrenoceptors and are present adjacent to NA varicosities in this region.4+ Bilateral vagotomy ameliorated the effects of sham operation on NA innervation; since the vagal nerve does not distribute fibers to the spleen, this effect is likely to occur through altered feedback circuits effecting sympathetic outflow, or through altered neuroendocrine outflow.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗
PubMed1988

Abnormalities in hypothalamic and neurohypophysial vasopressin content are not a consequence of hypertension in the spontaneously hypertensive rat.

In order to determine if the decreased hypothalamic and increased posterior pituitary content of vasopressin (VP) observed previously in spontaneously hypertensive rats (SHR) were a secondary consequence of the hypertension, the effect of preventing the development of hypertension on VP content of the hypothalamoneurohypophyseal system was evaluated. Two methods for preventing the hypertension were used: (1) chronic angiotensin-converting enzyme inhibition (oral captopril, 100 mg/kg/day at 4-12 weeks of age); and (2) intraventricular 6-hydroxydopamine (6-OHDA, 200 micrograms at 4 and 5 weeks of age). Both of these treatments markedly attenuated the increase in systolic blood pressure in SHRs at 5-11 weeks of age. The captopril-treated rats had a significant elevation in serum renin activity at 12 weeks of age indicating the presence of chronic converting enzyme inhibition, and the 6-OHDA-treatment resulted in a depletion of hypothalamic (86%) and brainstem (76%) norepinephrine content. Hypothalamic VP content was reduced in untreated SHRs compared to normotensive Wistar-Kyoto rats (WKYs, P = 0.0015). It was not significantly altered in either strain by the 6-OHDA treatment. Captopril caused a reduction in hypothalamic VP content in both SHRs and WKYs (P less than 0.01). Posterior pituitary VP content was elevated in untreated SHRs compared to WKYs (P less than 0.001), and remained elevated with captopril and 6-OHDA treatments. These data indicate that the abnormalities in VP content in the hypothalamus and posterior pituitary of SHRs are not a response to the hypertension. Therefore, they may represent primary abnormalities in the SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Maintenance of noradrenergic sympathetic innervation in the involuted thymus of the aged Fischer 344 rat.

Sympathetic postganglionic noradrenergic (NA) fibers innervate both primary and secondary lymphoid organs in the rat. In secondary lymphoid organs such as the spleen and lymph nodes, this innervation diminishes with age. This study was undertaken to determine whether a similar decline in NA innervation occurs in the thymus. Thymuses from Fischer 344 (F344) rats were examined at 3, 8, 12, 17, 21, and 27 months of age with fluorescence histochemistry for catecholamines, and with high-performance liquid chromatography with electrochemical detection (LCEC) for quantitation of monoamines. In adult animals of all age groups, the compartmentation of NA innervation was maintained; NA fibers entered the thymus with the vasculature and arborized in the cortex, particularly in the subcapsular region and around the vasculature at the corticomedullary junction. NA nerve fibers were sparse in the thymuses from 3-month-old rats and increased in density at 8 and 12 months of age. The density of NA nerve fibers in the thymuses from 17, 21, and 27 months of age increased further, in parallel with thymic involution. Quantitation of monoamines revealed stable thymic norepinephrine (NE) and 5-hydroxytryptamine (5-HT) content from 8 to 27 months of age. The lower levels of NE detected at 3 months of age may reflect a slow maturation and reorganization of this fiber system as a developmental phenomenon. Measurement of 3-methoxy-4-hydroxy-phenyleneglycol (MHPG), a major metabolite of NE, showed a more than twofold rise from 3 to 12 months of age, and remained high through 27 months of age. The resultant MHPG/NE ratios, as an index of NE availability for interaction with target cells, showed a decline from 3 months of age through 17-21 months of age, followed by a marked rise at 27 months of age. These findings suggest that the thymus is able to maintain NA innervation in the face of involution, and that these fibers provide a NA-enriched microenvironment for interaction with adrenergic receptors on thymocytes.

Adrenergic Fibers↗
PubMed1987

Noradrenergic sympathetic innervation of the spleen: I. Nerve fibers associate with lymphocytes and macrophages in specific compartments of the splenic white pulp.

Sympathetic noradrenergic nerve fibers, stained with antiserum for tyrosine hydroxylase (TH), richly innervate the splenic white pulp. These fibers distribute with the vascular and trabecular systems, and associate mainly with the central artery and its branches, the periarteriolar lymphatic sheath (PALS), the marginal sinus, and the parafollicular zone, with occasional delicate fibers also present in the follicles. Simultaneous staining of TH-positive nerve fibers and markers for specific lymphoid cells has shown several regions of contact between nerves and lymphocytes or macrophages. The TH-positive nerve fibers in the plexuses around the central arterial system and in the PALS are present among T lymphocytes (OX-19-positive cells) including both T helper and T suppressor cells, and interdigitating cells. At the marginal sinus, TH-positive fibers run adjacent to macrophages (ED3-positive cells), B lymphocytes (IgM-positive), and intensely fluorescent IgM-positive cells. Along the parafollicular zone, TH-positive nerve fibers run adjacent to T lymphocytes, peripheral follicular B lymphocytes, and intensely fluorescent IgM-positive cells. Within some follicles, delicate fibers end adjacent to both T and B lymphocytes. These relationships suggest a direct interaction between norepinephrine release from the TH-positive nerve terminals and the lymphocytes and macrophages closely associated with them, and focuses attention on the potential neural modulation of related functions such as T and B lymphocyte entry into the spleen and antigen capture (marginal zone), antigen presentation and T cell activation (PALS), B cell activation (parafollicular zone and marginal zone), and lymphocyte egress (outer marginal zone).

Animals↗
PubMed1987

Noradrenergic sympathetic innervation of the spleen: II. Tyrosine hydroxylase (TH)-positive nerve terminals form synapticlike contacts on lymphocytes in the splenic white pulp.

Immunocytochemistry was used to demonstrate tyrosine hydroxylase (TH)-positive profiles in the spleen of the adult Fischer 344 rat. At the light microscopic level, numerous varicose nerve profiles were seen in the white pulp, particularly surrounding the central arteries and their arteriole branches. At the electron microscopic level, varicosities were seen in close proximity to smooth muscle cells of the arteries, and directly abutting lymphocytes (presumable T-lymphocytes) of the nearby periarteriolar lymphatic sheath. There were no intervening cell processes between the TH-positive terminals and the lymphocyte. The opposing membranes were smooth and evenly spaced approximately 6 nm apart. Additional TH-positive nerve profiles were seen in the inner marginal zone and within trabeculae. The correlation between this immunocytochemical staining and previously demonstrated histofluorescence for norepinephrine leads to the conclusion that lymphocytes in the splenic white pulp have direct associations with noradrenergic fibers of the sympathetic nervous system. This association provides a route by which the autonomic nervous system could directly influence specific immune system effector cells.

Animals↗
PubMed1987

Noradrenergic sympathetic innervation of the spleen: III. Development of innervation in the rat spleen.

The ontogeny of noradrenergic innervation and its compartmental development were studied in the rat spleen using glyoxylic acid histofluorescence and high-performance liquid chromatography (HPLC). Noradrenergic nerves were present at birth in bundles adjacent to the splenic artery and vein. On days 1-3, fluorescent profiles largely were associated with the vasculature and with the perivascular zone. By day 6, these fibers formed increasingly elaborate and tortuous plexuses around the central arteries and their branches. By day 10, fibers were present along the marginal sinus and extended into the developing marginal zone. Between day 10 and day 13 the largest increase in norepinephrine (NE) levels (per mg protein) were noted, and the periarteriolar lymphatic sheath (PALS) achieved its adult form, with increased innervation of the parenchyma. In contrast, the venous/trabecular system developed relatively late. The first trabecular fibers were evident at day 10, and the capsule was not innervated until day 13. From 13 days to adulthood, there was a gradual refinement and extension of existing patterns with no change in NE levels as measured by HPLC (per mg protein), suggesting that the innervation was keeping pace with rapid increases in spleen growth. The pattern of growth and development for noradrenergic nerves in the PALS remarkably parallels changes in T cell compartmentation during this period. We propose that norepinephrine is available for interaction with T cells at the earliest stages of development and could play a role in such processes as lymphocyte packing and the onset of immunocompetence.

Aging↗
PubMed1987

Noradrenergic sympathetic innervation of the spleen: IV. Morphometric analysis in adult and aged F344 rats.

Noradrenergic postganglionic sympathetic innervation of the spleen in 8-month-old (adult) and 27-month-old (aged) Fischer 344 (F344) rats was examined using fluorescence histochemistry for catecholamines coupled with stereologic point-counting analysis for quantitation of noradrenergic varicosities. Noradrenergic varicosities in the spleen were evaluated in four compartments: (1) vascular-, (2) trabecular-, (3) capsular-, and (4) parenchymal-associated fibers. The 27-month-old rats were subdivided further into two groups based upon behavioral testing for gustatory neophobia, a condition reported to be associated with acute locus coeruleus lesions in young rats and with diminished norepinephrine (NE) levels in central noradrenergic neurons in aged rats. In the 8-month-old rats, spleens displayed abundant innervation. Noradrenergic plexuses entered the spleen with the splenic artery and its branches, distributed into capsular and trabecular compartments, and followed the vasculature and trabeculae into splenic white pulp. Noradrenergic fibers entered the white pulp mainly in association with the central artery and its branches; liner and punctate varicosities branched mainly from vascular plexuses into the large, well-defined parenchyma of the white pulp, ending primarily among fields of T lymphocytes. Some fibers extended along the inner edge of the marginal zone and the parafollicular zone. Few noradrenergic varicosities were found in the red pulp. In both groups of aged rats, sympathetic noradrenergic innervation was diminished markedly.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗