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S Y Felten

Publications and source records attributed to S Y Felten.

At least 37 records · Page 2Linked to original sources
PubMed1993

Splenic norepinephrine is decreased in MRL-lpr/lpr mice.

The MRL-lpr/lpr mouse, a genetic model of the human autoimmune disease systemic lupus erythematosus, has been studied extensively to determine the etiology and the pathological course of the disease in lymphoid organs. At approximately 8 weeks of age, splenomegaly develops due to a massive increase in an abnormal population of T cells, resulting in a disruption of the normal splenic architecture. Part of the normal splenic architecture includes postganglionic noradrenergic sympathetic nerve fibers, which can exert influence on a variety of immunological functions. Noradrenergic innervation and norepinephrine content of spleens from both male and female MRL-lpr/lpr mice and MRL(-)+/+ congenic controls were examined at 6, 12, 18, and 24 weeks of age. Norepinephrine content is reduced in MRL-lpr/lpr male and female mice prior to the onset of observed splenomegaly and remains reduced at all ages examined. Remaining noradrenergic fibers are found in their usual compartments, but are greatly diminished compared with controls.

Adrenergic Fibers↗
PubMed1993

Acetylcholinesterase staining and choline acetyltransferase activity in the young adult rat spleen: lack of evidence for cholinergic innervation.

Acetylcholinesterase (AChE) staining in spleens from young adult Sprague-Dawley rats was examined following several denervation paradigms to determine the source of splenic AChE+ nerve fibers. In spleens from all control groups, AChE+ neural-like profiles were present along the vasculature and in the trabeculae. AChE+ reactivity also was present in lymphoid and reticular cells in the spleen, and in neuronal cell bodies in the superior mesenteric-coeliac ganglion (SM-CG). Neurochemical analysis revealed no significant choline acetyltransferase activity in spleens from control animals. Surgical removal of the SM-CG resulted in a total loss of both noradrenergic (NA) and AChE+ nerve profiles, as well as a loss of AChE staining in nonneural compartment in the spleen. On Days 1 and 3 after treatment, chemical sympathectomy with 6-hydroxydopamine also resulted in a loss of both NA and AChE nerve profiles in the spleen, except for a few resistant fibers in the hilar region. AChE reactivity in nonneural compartments also was diminished in chemically denervated regions of the spleen. AChE staining in both neural and nonneural profiles progressively increased from 10 to 56 days after chemical sympathectomy, with a time course and distribution pattern similar to NA fibers reinnervating the spleen. AChE+ staining was preserved following bilateral vagal nerve transection. The miniscule splenic levels of choline acetyltransferase suggest that at best, only a small density of cholinergic nerves distribute to the rat spleen. Further, what cholinergic innervation is present does not arise from the vagus nerve as suggested in the earlier literature. Collectively, the overlapping distribution of AChE+ and NA nerve profiles in spleen and parallel loss of both population of nerve fibers following surgical and chemical sympathectomy support the presence of AChE in NA nerves colocalized with norepinephrine, and thus make AChE+ staining an inappropriate marker for cholinergic innervation in the rat spleen.

Acetylcholinesterase↗
PubMed1993

Neonatal sympathetic denervation alters development of natural killer (NK) cell activity in F344 rats.

The development of natural killer (NK) cell activity was assessed in Fischer 344 (F344) rats sympathectomized as neonates with the neurotoxin, 6-hydroxydopamine (6-OHDA). No NK cell activity was detected in sympathectomized or vehicle-injected control animals at 7 days of age. At 10 and 14 days of age, NK cell activity was reduced in spleens from sympathectomized male and female rats. At 21 days of age, a reduction in NK cell activity was detected only in sympathectomized male rats. Sympathectomy did not alter NK cell activity at 28 and 42 days of age in either gender. At 56 days of age, NK cell activity was increased in neonatally sympathectomized females; rats of both genders acutely sympathectomized at 56 days of age also showed enhanced NK cell activity. No differences were observed at 90 days of age in neonatally or acutely sympathectomized males of females. Prior treatment with desipramine, which blocks uptake of 6-OHDA into nerve terminals and prevents the destruction of sympathetic nerve terminals, prevented these 6-OHDA-induced effects, suggesting that sympathectomy, and not direct toxic effects of 6-OHDA treatment of NK cells, accounted for the alterations in NK cell activity. Together, these results indicate that the sympathetic nervous system is an integral component of the developing lymphoid and hematopoietic microenvironment.

Aging↗
PubMed1993

Fundamental aspects of neural-immune signaling.

Noradrenergic and peptidergic nerve fibers abundantly innervate the parenchyma of both primary (bone marrow) and secondary (spleen, lymph nodes) lymphoid organs. Nerve fibers distribute within the parenchyma of these organs, as well as along smooth muscle compartments. Both noradrenaline and peptides such as substance P have been shown to fulfill the basic criteria for neurotransmission with lymphocytes, macrophages, and other immunocytes as targets. Denervation or pharmacological manipulation of these neurotransmitters can profoundly alter immunological reactivity at the individual cellular level, at the level of complex multicellular interactions (such as antibody response), and at the level of host response to a disease-producing challenge. The characteristic and mechanisms of bidirectional neural-immune signaling may provide a novel approach to immunologically-mediated disease, both pharmacologically and behaviorally.

Female↗
PubMed1993

Cardiac noradrenergic nerve terminal abnormalities in dogs with experimental congestive heart failure.

BACKGROUND: We have shown previously that norepinephrine (NE) uptake activity is reduced in the failing right ventricle of animals with right heart failure (RHF) produced by tricuspid avulsion and progressive pulmonary constriction. However, it is unknown whether this defect in neuronal NE uptake is related to reduction of noradrenergic nerve terminals or whether these changes also occur in animals with left heart failure (LHF). It is also unknown whether increased NE release in heart failure contributes to the noradrenergic nerve abnormalities. METHODS AND RESULTS: We measured myocardial NE content. NE uptake function, and noradrenergic nerve profiles in dogs with either RHF or LHF induced by rapid ventricular pacing. NE uptake activity was measured using [3H]NE, and noradrenergic nerve profiles were visualized by glyoxylic acid (SPG)-induced histofluorescence and tyrosine hydroxylase immunocytochemical staining. To study the effects of excess NE, we exposed normal dogs to 8 weeks of chronic NE infusion using subcutaneous osmotic minipumps. RHF and LHF animals exhibited reduced myocardial contractile function and congestive heart failure, as evidence by reduced cardiac output and elevated right atrial pressure. However, unlike that in LHF, left atrial pressure was not increased in RHF. The animals also showed an increase in plasma NE and a decrease in cardiac NE. In addition, SPG-induced histofluorescence correlated significantly with NE uptake activity (r = .712, P < .001) and tyrosine hydroxylase immunoreactive profiles (r = .569, P < .001) in the right ventricles of RHF dogs and in both ventricles of LHF dogs. The numbers of catecholaminergic profiles and tyrosine hydroxylase profiles significantly correlated with cardiac filling pressures. Chronic infusion of NE decreased heart rate in normal dogs but had no effect on either mean aortic pressure or left atrial pressure; like heart failure, it resulted in significant decreases in myocardial NE uptake activity and numbers of SPG-induced catecholaminergic histofluorescence and immunoreactive tyrosine hydroxylase profiles. CONCLUSIONS: Myocardial NE uptake activity was reduced only in the failing ventricles with elevated filling pressure in RHF and LHF. These changes probably were caused by loss of noradrenergic nerve terminals in the failing ventricles, as evidenced by the reductions of catecholaminergic histofluorescence and tyrosine hydroxylase immunostained profiles. Furthermore, since similar reductions of myocardial NE uptake and noradrenergic nerve profiles could be produced by chronic NE infusion in normal dogs, elevated NE levels may play a role in the development of cardiac noradrenergic nerve abnormalities in congestive heart failure.

Animals↗
PubMed1993

Developmental assessment of hypothalamic tuberoinfundibular dopamine in prolactin-deficient dwarf mice.

Development of the hypophysiotropic hypothalamus in PRL-deficient Ames dwarf (df/df) mice was examined for steady state dopamine (DA) by visualization using formaldehyde-induced catecholamine histofluorescence and by quantification using catecholamine HPLC at selected postnatal ages (7, 14, 21, 30, and 90 days). Phenotypically normal (DF/?) littermate mice were compared with dwarfs by both methods at each age. The studies were designed to investigate whether the known deficiency in hypothalamic tuberoinfundibular DA in adult dwarfs is present neonatally or develops over the postnatal period. The anterior pituitary of each mouse was processed for GH and PRL immunocytochemistry. At 7 days of age, GH immunostaining was robust, and scattered PRL-positive cells were noted in DF/? pituitary. Homogeneously distributed PRL cells increased in number through 30 days of age in normal mice. Neither GH nor PRL immunoreactivity was present in df/df mice at any age. At 7, 14, and 21 days of age, hypothalamic DA tuberoinfundibular histofluorescence was comparable in df/df and DF/? mice. At 90 days of age, tuberoinfundibular histofluorescence in normal mice remained intense, but was virtually undetectable in dwarfs. The developmental change affected only tuberoinfundibular neurons, since DA histofluorescence in nonhypophysiotropic areas, such as substantia nigra (SN), was qualitatively comparable for df/df and DF/? for all ages examined. Norepinephrine (NE) fluorescence in hypothalamus was also comparable for df/df and DF/?. Catecholamine HPLC provided quantitative confirmation of histofluorescence observations. DA and NE levels in both hypothalamus and ventral midbrain, including SN, increased during development in both df/df and DF/? brains. NE levels were not different between dwarf and normal animals at any age in either medial basal hypothalamus (MBH) or SN. The DA concentration in SN was not different between df/df and DF/? at any age examined. MBH DA was comparable in df/df and DF/? mice at 7, 14, and 21 days of age; at 30 and 90 days, MBH DA was markedly lower (P < 0.001) in dwarf than in normal mice. Although MBH DA in dwarfs was comparable to that in normal mice at 21 days, the increase in dwarfs between 14 and 21 days was not statistically significant. Thus, the hypothalamic DA deficit that exists in adult dwarf mice is not present neonatally and represents a failure to increase DA compared with normal mice after 14 days of age. The failure of continued development of hypophysiotropic tuberoinfundibular DA neurons in dwarf mice is correlated chronologically with absent pituitary PRL production.

Animals↗
PubMed1992

Age-related decline in the dopaminergic nigrostriatal system: the oxidative hypothesis and protective strategies.

The anatomical and metabolic deterioration of the dopaminergic (DA) nigrostriatal system with age has been hypothesized to occur due to autodestruction by reactive oxygen intermediates derived from oxidative metabolites of DA. We hypothesized that treatment with a presynaptic agonist to diminish DA turnover should confer a protective effect. Pergolide mesylate, a potent D2 agonist with predominantly presynaptic action, when given in the diet (0.5 mg/kg/day) to male Fischer 344 rats from 3 months of age to 26 months of age, preserved the integrity of both cell bodies and terminals of the nigrostriatal system, partially reversed the age-related decline in DA uptake, and had no adverse effects on behavior or postsynaptic DA receptors on striatal neurons compared with age-matched, pair-fed control rats. As a counterpart to this strategy, L-dopa administration (50 mg/kg) to adult male Fischer 344 rats with unilateral nigrostriatal lesions using 6-hydroxy-dopamine, and subsequent fetal mesencephalic grafts resulted in stunted size and neurite outgrowth, diminished tyrosine hydroxylase (TH) expression, diminished behavioral recovery, and diminished ability to reverse lesion-induced D2 receptor changes, compared with saline-treated rats with the same lesion and subsequent graft. This toxic effect, although not seen in intact nigrostriatal systems, may indicate L-dopa toxicity on transplanted DA cells, or on DA cells maximally activated to recover from insult. In 3-month-old male C57BL/6 mice with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions, spontaneous recovery of the damaged DA nigrostriatal system was seen within 12 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

A longitudinal study of age-related loss of noradrenergic nerves and lymphoid cells in the rat spleen.

A longitudinal study of sympathetic noradrenergic (NA) innervation of the spleen was carried out in 3-, 8-, 12-, 17-, 21-, and 27-month-old Fischer 344 (F344) rats using (i) fluorescence histochemistry for localization of norepinephrine (NE); (ii) immunocytochemistry (ICC) for localization of tyrosine hydroxylase (TH)-positive nerve fibers alone, and in combination with specific markers for T and B lymphocytes (OX19 and anti-mu respectively), and macrophages (ED3); and (iii) high-performance liquid chromatography with electrochemical detection for quantitation of NE. Fluorescence histochemistry revealed extensive loss of NA nerve fibers in all compartments of the spleen in 21- and 27-month-old rats. With single-label ICC, a decline in TH+ nerve fibers in all compartments of the spleen was observed by 17 months of age and became more severe with advancing age; these findings suggest that both the rate-limiting enzyme and the transmitter itself (NE) are depleted from sympathetic nerves in aged rat spleen. Double-label ICC demonstrated the loss of TH+ nerve fibers in spleen from 17-, 21-, and 27-month-old rats, and a parallel loss of OX19+ T lymphocytes and ED3+ macrophages in these cellular compartments. Neurochemical measurement of NE demonstrated a decline in NE per wet weight at 27 months of age. The age-related decline in NA innervation of spleen and in the density of specific populations of cells of the immune system (T lymphocytes and antigen-presenting ED3+ macrophages), that follow remarkably similar time courses, supports functional evidence for dynamic interactions between the immune system and NA sympathetic nerves in the spleen, and further suggests a causal relationship between these age-related phenomena, i.e., that age-related immunosenescence promotes sympathetic denervation of the spleen which further compromises immune function. This hypothesis, however, requires further testing.

Aging↗
PubMed1992

Sympathetic nervous system modulation of tumor metastases and host defense mechanisms.

The sympathetic nervous system can signal cells of the immune system through release of norepinephrine (NE), and may thus modulate several aspects of immune reactivity. We have examined the consequences of chemical denervation using 6-hydroxydopamine (6-OHDA) on the response of BALB/c mice to tumor cell challenge. In this study, chemical axotomy prior to the intravenous (i.v.) injection of the alveolar carcinoma line 1 significantly increased the number of pulmonary metastases. In contrast, axotomy performed after i.v. injection of tumor cells had no effect on the number of lung metastases. Line 1 tumor cells have been reported to be susceptible to lysis by natural killer (NK) cells. To examine possible mechanisms through which prior axotomy leads to increased lung metastases, we tested the effects of axotomy on in vitro and in vivo NK cell activity. No differences in NK cell activity were found between 6-OHDA- and vehicle-treated mice. Line 1 tumor cell growth in vitro was unaffected by both 6-OHDA and NE, and the tumor cells do not express beta-adrenergic receptors. Priming mice with lethally irradiated line 1 cells significantly reduced the number of lung metastases following challenge with live tumor cells; axotomy did not alter this decrease in metastases associated with priming. In summary, chemical axotomy of mice prior to injection of alveolar carcinoma cells resulted in an increased number of pulmonary metastases that was not correlated with alterations in either NK cell cytotoxicity or the putative immunological consequences of in vivo priming.

Animals↗
PubMed1992

Innervation of lymphoid organs and implications in development, aging, and autoimmunity.

We now have substantial evidence demonstrating noradrenergic sympathetic and peptidergic innervation of both primary and secondary lymphoid organs. We have established criteria for norepinephrine, and some of the neuropeptides, as neurotransmitters, and have found changes in immune responsiveness following pharmacological manipulation of noradrenergic sympathetic or peptidergic nerves. Classic receptor binding studies have demonstrated a wide variety of target cells that possess beta-adrenoceptors and receptors for neuropeptides on cells of the immune system, including lymphocyte subsets, macrophages, accessory cells, or stromal elements. In this chapter we describe noradrenergic and peptidergic innervation of primary and secondary lymphoid organs in development, at maturation and during the normal aging process, and discuss possible functional implications of direct neural signals onto cells of the immune system at critical time points in the lifespan of an animal. Further, we examine for involvement of noradrenergic sympathetic and peptidergic innervation in the development and progression of several autoimmune disorders, including adjuvant-induced arthritis, New Zealand mice strains as a model for hemolytic anemia and lupus-like syndrome, and the experimental allergic encephalomyelitis model for multiple sclerosis.

Adrenergic Fibers↗
PubMed1992

Noradrenergic and peptidergic innervation of secondary lymphoid organs: role in experimental rheumatoid arthritis.

Noradrenergic (NA) and peptidergic nerve fibres are present in both primary and secondary lymphoid organs, distributing with the vasculature, trabecular and capsular smooth muscle, and within the parenchyma among cells of the immune system. NA nerve terminals directly abut lymphocytes and macrophages in spleen and lymph nodes. In these organs, norepinephrine has fulfilled the basic criteria for neurotransmission with cells of the immune system as targets. In vitro and in vivo studies have demonstrated NA modulation of primary and secondary antibody responses, cytotoxic T cell responses, natural killer cell activity, and proliferation and differentiation of both T and B lymphocytes. Substance P (SP) has been shown to modulate inflammatory responses, lymphocyte proliferation, and other immunologic reactivity. We investigated the role of NA and SP nerve fibres within lymph nodes in experimental allergic auto-immune arthritis in Lewis rats. Denervation of NA nerve fibres in popliteal and inguinal lymph nodes with 6-hydroxy-dopamine resulted in earlier onset and enhanced severity of arthritic changes as well as inflammation in bilaterally induced experimental arthritis, while denervation of SP nerve fibres in popliteal and inguinal lymph nodes with capsaicin resulted in delayed onset and diminished severity of the inflammatory changes ipsilaterally, and prevention of contralateral arthritic changes in unilaterally induced experimental arthritis. These findings suggest that NA and SP nerve fibres in lymph nodes can modulate the time course of onset and the severity of experimental arthritis in Lewis rats. These modulatory effects are distinctly different from the effects of NA and SP nerve fibres in the joints themselves.

Animals↗
PubMed1991

The nigrostriatal dopaminergic system in MPTP-treated mice shows more prominent recovery by syngeneic adrenal medullary graft than by allogeneic or xenogeneic graft.

Following systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), young (2-month-old) C57BL/6 mice show decreased dopaminergic (DA) nigrostriatal fibers and DA concentration in the striatum. We transplanted syngeneic, allogeneic and xenogeneic adrenal medullary grafts into the striatum of the MPTP-treated young mice and compared the survivability of grafted chromaffin cells and the recovery of intrinsic host DA fibers using computerized image analysis of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers and high performance liquid chromatography with electrochemical detection (LCEC). The grafted syngeneic adrenal chromaffin cells survived better than allogeneic or xenogeneic chromaffin cells, and host DA nigrostriatal fiber recovery was more prominent in mice with a syngeneic graft than in mice with an allogeneic or xenogeneic graft. However, the degree of host fiber recovery in mice with allogeneic or xenogeneic mice was greater than in mice with a sham operation alone, even though the allografts and xenografts had no surviving chromaffin cells. Allografts and xenografts showed prominent rejection responses, with T lymphocyte infiltration in addition to macrophages. We conclude that a syngeneic adrenal graft survives better than an adrenal allograft or xenograft and promotes recovery of the intrinsic host nigrostriatal DA fibers. We also conclude that grafted chromaffin cell survivability influences the degree of host DA fiber recovery following MPTP depletion. Adrenal medullary grafts to Parkinsonian patients are currently under way in a large number of hospitals; we suggest that greater attention be paid to methods which lead to enhanced survival of the grafted chromaffin cells, since survivability might be closely related to the functional recovery of these patients.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Stereotaxic injection of GD1a ganglioside induces limited recovery of striatal dopaminergic system in MPTP-treated aging mice.

The systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to young (2 months old) and aging (12 months old) C57BL/6 mice (4 x 20 mg/kg i.p. given 12 hr apart) reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum and reduced dopamine (DA) concentration to 35% of controls in young and 22% of controls in aging mouse brain 5 weeks after administration. Stereotaxic injection of GD1a ganglioside (3 x 100 micrograms, 5 days apart) into the striatum of MPTP-treated young mice restored striatal DA concentration to 52% of the control concentration 5 weeks after MPTP injection. Similar injections of GD1a ganglioside restored striatal DA concentration of MPTP-treated aging mice to only 31% of the control concentration. Immunocytochemical analysis showed significant recovery of TH-IR fibers in the striatum of MPTP-depleted young mice treated with GD1a ganglioside, while TH-IR fibers in the striatum of MPTP-depleted aging mice treated with GD1a ganglioside showed less recovery. We conclude that treatment of MPTP-depleted aging mice with GD1a ganglioside results in more limited recovery in the nigrostriatal DA system than in young mice.

Aging↗
PubMed1991

Substance P innervation of spleen in rats: nerve fibers associate with lymphocytes and macrophages in specific compartments of the spleen.

We investigated the distribution of SP+ nerve fibers in the spleen of adult male Fischer 344 rats. SP+ nerve fibers entered the spleen with the splenic artery in the hilar region, arborized along the venous sinuses, and extended from these larger plexuses into trabeculae and the surrounding red pulp. In the white pulp, SP+ nerve fibers were found in the marginal zone, and in the outer regions of the PALS among T lymphocytes. No SP+ nerve fibers were observed in association with the splenic capsule, the central arteries of the white pulp, or the follicles. SP levels in rat spleen were 5.7 +/- 0.4 ng/g wet wt. On the basis of the present findings of SP presence in nerve fibers in the spleen, and published evidence for SP receptors on lymphocytes and macrophages, we suggest that SP derived from nerve fibers in the spleen can act as a neurotransmitter with cells of the immune system as targets. These SP nerve fibers may be an important neural link between the nervous system and the immune system and may participate in modulation of immune reactivity and inflammatory responses.

Animals↗
PubMed1991

Neuropeptide-Y innervation of the rat spleen: another potential immunomodulatory neuropeptide.

Neuropeptide-Y (NPY) is a 36 amino acid peptide that acts as a chemical messenger in the central and peripheral nervous systems. NPY often is found colocalized with the classical neurotransmitter norepinephrine (NE) and can potentiate the effects of this neurotransmitter postsynaptically in many systems. Using immunocytochemistry for NPY and specific lymphoid cell markers, we mapped the distribution of NPY-positive nerve fibers in the rat spleen. NPY-positive nerve fibers were present along the vasculature, trabeculae, and capsule, and also were found associated with specific lymphoid parenchymal compartments of the spleen, in close contact with lymphocytes and macrophages. These contacts were investigated further at the electron microscopic level. NPY-positive nerve terminals were found in close apposition with lymphocytes in the periarteriolar lymphatic sheath, and with lymphocytes and macrophages in the marginal zone. Previous studies have reported that postganglionic noradrenergic nerve fibers innervate specific lymphoid compartments of the rat spleen, with nerve terminals forming direct appositions with cells of the immune system. The possible colocalization of NPY and NE in these nerve fibers was investigated by chemical sympathectomy with 6-hydroxydopamine, followed by immunocytochemical labeling of NPY and tyrosine hydroxylase (TH), the rate-limiting enzyme in norepinephrine synthesis. Colocalization also was investigated by labeling for NPY with a fluorescent label, eluting the NPY, and staining for TH with diaminobenzidine as the label. These studies demonstrate that norepinephrine and NPY are colocalized in the postganglionic sympathetic nerve fibers of the rat spleen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Neonatal sympathetic denervation alters the development of in vitro spleen cell proliferation and differentiation.

The ontogeny of spleen cell proliferation to T and B cell mitogens and immunoglobulin secretion, measured in vitro, was examined in neonatally sympathectomized Fischer 344 (F344) rats, administered the neurotoxic drug 6-hydroxydopamine (6-OHDA) from 1 to 3 days of age. Compared to cells from age-matched controls, spleen cells from neonatally sympathectomized animals, aged 7-14 days, exhibited a shift in the proliferative response to the T cell mitogen, concanavalin A (Con A), with reduced proliferation in the presence of low doses of Con A, but increased proliferation with higher doses. During the same period, from 7 to 14 days, the B cell mitogen STM/DxS inhibited proliferation by spleen cells from all rats, and no effect of sympathectomy was observed. As adult-like patterns of mitogen responsiveness emerged from 21 to 42 days of age, neonatally sympathectomized rats showed reduced proliferative responses of both T and B cells. This effect dissipated by 56 days of age. Polyclonal immunoglobulin (Ig) production by B cells was assessed in vitro in the presence or absence of STM/DxS. Neonatal sympathectomy resulted in reduced spontaneous IgM production throughout development. From 28 to 42 days of age, when mitogen-triggered IgM secretion first developed, neonatal sympathectomy decreased the magnitude of the response. By 56 days of age, mitogen-induced IgM secretion was no longer affected by sympathectomy, similar to the proliferative response. Gender influenced the time course of sympathectomy-induced changes in spleen cell proliferation and differentiation; however, the magnitude and direction of these changes were similar in both males and females. Desipramine, administered prior to 6-OHDA, prevented both sympathetic denervation and the 6-OHDA-induced changes in spleen cell responsiveness. This indicates that the alterations in immune function were dependent on NA nerve fiber destruction and were not simply the result of direct 6-OHDA action on other cells. The results of this study suggest that sympathetic innervation may play an important potentiating role in the development of the lymphoid system, through effects on lymphocyte proliferation and differentiation.

Animals↗
PubMed1990

Cografts of adrenal medulla with peripheral nerve enhance the survivability of transplanted adrenal chromaffin cells and recovery of the host nigrostriatal dopaminergic system in MPTP-treated young adult mice.

Schwann cells from transected peripheral nerve segments are known to produce nerve growth factor (NGF). We performed adrenal medullary grafts or cografts of adrenal medulla and sciatic nerve into the striatum of MPTP-treated young adult mice, and compared the survivability of grafted chromaffin cells and the recovery of intrinsic host DA fibers using computerized image analysis of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers and neurochemical analysis with high performance liquid chromatography (HPLC). Adrenal medullary chromaffin cells cografted with sciatic nerve survived better than those in adrenal grafts alone; host DA fiber recovery was more prominent in mice with cografts than in mice with adrenal grafts alone. A large number of TH-IR surviving cells in cografted mice showed long neuronal processes which were rarely seen in the mice receiving adrenal graft alone. We conclude that cograft of adrenal medulla and sciatic nerve promotes intrinsic host DA fiber recovery better than adrenal medulla grafts alone, and that survivability of grafted chromaffin cell may promote host DA fiber recovery. Adrenal medullary autografts have been used in patients with Parkinson's disease; we suggest that if this approach is to be used in the future, methods to increase the survivability of grafted chromaffin cells, such as co-grafting with pieces of peripheral nerve, be considered to enhance the survivability of the chromaffin cells, which might be closely related to the functional recovery of the patients by this grafting procedure. Of course, such strategies as the present cografting approach must be demonstrated to work in older animals using older donor tissue before proceeding to this next step in humans.

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