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R E Zigmond

Publications and source records attributed to R E Zigmond.

At least 19 recordsLinked to original sources
PubMed1995

Changes in the macrophage population of the rat superior cervical ganglion after postganglionic nerve injury.

Following peripheral nerve transection, a series of biochemical changes occurs in axons and Schwann cells both at the site of the lesion and distal to it. Macrophages differentiated from monocytes that invade the area in response to transection (elicited macrophages) and, perhaps, also macrophages normally present in the tissue (resident macrophages) play important roles in these changes. In addition, nerve transection produces changes in the cell bodies of axotomized neurons and their surrounding glial cells, located at some distance from the lesion. To determine whether macrophages might play a role in the changes occurring in the superior cervical ganglion (SCG) after axotomy, we examined the presence of macrophages before and after axonal damage. The monoclonal antibodies ED1, ED2, and OX6 were used, each of which recognizes a somewhat different population of macrophages. Ganglia from normal rats contained a population of resident cells that were ED2+ but very few that were ED1+. Within 2 days after the post-ganglionic nerves were transected, the number of ED1+ cells increased substantially, with little change in immunostaining for ED2. These data, in combination with published studies on other tissues, suggest that ED1 in the SCG is selective for elicited macrophages and ED2 for resident macrophages. OX6 immunostaining was prominent in normal ganglia but also increased significantly after axotomy, suggesting that it reflects both macrophage populations. Systemic administration of 6-hydroxydopamine, a neurotoxin that causes the destruction of sympathetic nerve endings, also produced an increase in ED1 immunostaining. Thus, the change in ED1 immunostaining in the SCG does not require surgery, with the attendant severing of local blood vessels and connective tissue, but rather only the disconnection of sympathetic neurons from their end organs. The time course of the invasion of monocytes after axotomy indicates that this process is not required to trigger the biochemical changes occurring in the ganglion within the first 24 h. On the other hand, the existence of a resident population of macrophages raises the possibility that changes in those cells might be involved.

Animals↗
PubMed1995

Galanin expression in sympathetic ganglia after partial axotomy is highly localized to those neurons that are axotomized.

The neuropeptide phenotype of adult sympathetic neurons changes dramatically after postganglionic nerve transection. Studies, thus far, have been done on the superior cervical ganglion; however, one limitation of this preparation is that it is necessary to transect the postganglionic axons quite close to the ganglion. In the present study, we examined the effects of axonal damage on galanin-like immunoreactivity in the middle and inferior cervical ganglion complex. With these ganglia, it is possible to transect postganglionic axons at a considerable distance from their cell bodies and, therefore, to examine the extent to which local tissue damage, rather than specific axonal transection, is required for these changes in neuropeptide phenotype to occur. The anatomy of this system also allowed us to determine the extent to which the changes in galanin expression are restricted to those neurons that have been axotomized. The axons of a small population of the neurons in the middle and inferior cervical ganglia complex project into the cervical sympathetic trunk. Within two days after this trunk was transected, there was an increase in the level of galanin-like immunoreactivity in the complex and in the number of immunostained principal neurons. These neurons were concentrated primarily in the most rostral part of the complex. An increase in galanin-like immunoreactivity also occurred in response to the systemic administration of the sympathetic neurotoxin 6-hydroxydopamine. In that case, many more neurons were affected than after transection of the cervical sympathetic trunk, and the neurons were distributed evenly throughout the ganglion complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗
PubMed1994

Galanin and vasoactive intestinal peptide messenger RNAs increase following axotomy of adult sympathetic neurons.

The adult rat superior cervical ganglion (SCG) contains low levels of galanin- and vasoactive intestinal peptide-(VIP) like immunoreactivity, with very few immunostained principal neurons. Immunoreactivity for both neuropeptides increases in these neurons after explantation or postganglionic axotomy in vivo. Northern blot analysis has demonstrated concomitant increases in mRNAs encoding these peptides. To localize cells in axotomized ganglia which increase their expression of these mRNAs, we performed in situ hybridization studies. In control SCG, only a few principal neurons contained mRNA for either galanin or VIP. After 48 h in organ culture, galanin mRNA was expressed in the majority of principal neurons. At 48 h after in vivo axotomy of both postganglionic trunks of the SCG, the internal and external carotid nerves, the distribution and number of neurons, expressing galanin mRNA increased similarly to that seen in culture. Lesioning either trunk alone produced increases in galanin mRNA localized to those regions of the ganglion containing neurons that project into the lesioned trunk. Transection of the predominantly preganglionic cervical sympathetic trunk increased galanin mRNA expression in a small population of neurons near that nerve trunk. The distributions of these labeled neurons, together with previous neuroanatomical studies, suggests that they had been axotomized by the lesions. Similar studies examining VIP mRNA expression demonstrated that although considerably fewer VIP mRNA expressing neurons than galanin mRNA expressing neurons were present after axotomy, the distribution of neuropeptide mRNA-positive cells were similar in both cases. These observations suggest that increases in the peptides galanin and VIP after nerve transection result from changes in the levels of their mRNAs in those neurons that have been axotomized.

Animals↗
PubMed1994

Regulation of vasoactive intestinal peptide expression in sympathetic neurons in culture and after axotomy: the role of cholinergic differentiation factor/leukemia inhibitory factor.

Vasoactive intestinal peptide (VIP) expression increases in sympathetic neurons when they are grown in dissociated cell or explant cultures and when they are axotomized in vivo. In dissociated cell culture, the magnitude of the VIP increase was reduced when nonneuronal cells were removed and medium conditioned by ganglionic nonneuronal cells increased VIP in neuron-enriched cultures. Antiserum against cholinergic differentiation factor (also leukemia inhibitory factor; CDF/LIF), but not against ciliary neurotrophic factor, immunoprecipitated this activity. Medium conditioned by sympathetic ganglion explants also contained a VIP-stimulatory molecule that was immunoprecipitated by CDF/LIF antiserum, and CDF/LIF antiserum partially blocked VIP induction in explants. CDF/LIF mRNA was increased in dissociated cell cultures, in ganglion explants and in vivo after axotomy. Our results suggest that CDF/LIF released from ganglionic nonneuronal cells plays an important role in regulating VIP after axotomy.

Animals↗
PubMed1994

Galanin expression increases in adult rat sympathetic neurons after axotomy.

Changes in neuropeptide expression occur in sensory, motor, and sympathetic neurons following axotomy. The particular pattern of peptide changes that occurs varies among the three cell types. We have studied the regulation in the rat superior cervical ganglion of the expression of galanin, a peptide previously shown to increase in axotomized sensory and motor neurons. While normally only an occasional neuron exhibiting galanin-like immunoreactivity is found in this ganglion, at two days after transection of the postganglionic internal and external carotid nerves, immunostaining can be observed in many neurons throughout the ganglion. Similar changes are found when ganglia are placed in organ culture for two days. The distribution of immunostained neurons after section of only one of the postganglionic trunks suggests that changes in galanin-like immunoreactivity occur only within neurons whose axons are transected. None the less, even when both nerve trunks are transected, only about half of the neurons in the ganglion exhibit galanin-like immunoreactivity, indicating that only a proportion of the axotomized neurons exhibit a detectable response. The few immunostained neurons seen after section of the cervical sympathetic trunk may also represent axotomized neurons. Galanin-like immunoreactivity extracted from the ganglion co-chromatographs with authentic galanin, and the level of this immunoreactivity increases dramatically after axotomy and explantation, and modestly after decentralization. These same manipulations produce parallel increases in the level of galanin messenger RNA. Together, the findings indicate that the expression of galanin increases in sympathetic neurons after axotomy. Galanin is thus the first neuropeptide whose expression has been shown to increase after transection of all three types of peripheral axons that have been studied.

Animals↗
PubMed1993

Vasoactive intestinal peptide and secretin produce long-term increases in tyrosine hydroxylase activity in the rat superior cervical ganglion.

Electrical stimulation of the preganglionic fibers innervating the rat superior cervical ganglion (SCG) produces both short-term and long-term increases in tyrosine hydroxylase (TH) activity that are not completely blocked by nicotinic antagonists. Vasoactive intestinal peptide (VIP) and secretin, two neuropeptides known to produce short-term increases in TH activity, were examined for their ability to produce long-term increases in this enzyme activity. Culturing the SCG in the presence of either peptide produced a 30-50% increase in TH activity measured 2 days later. The results raise the possibility that one of these peptides or a related molecule participates in the transsynaptic induction of ganglionic TH.

Animals↗
PubMed1993

Regulation of substance P is similar to that of vasoactive intestinal peptide after axotomy or explantation of the rat superior cervical ganglion.

The regulation of the expression of substance P (SP) in the rat superior cervical ganglion was compared to that of vasoactive intestinal peptide (VIP) in vivo after axotomy and in vitro after explantation. Previous studies have demonstrated that both neuropeptides increase after explantation, depolarization, and decentralization; however, whereas VIP expression increases after postganglionic axotomy, SP expression reportedly does not. To compare the effect of axotomy on these two peptides directly, the content of both was determined in individual ganglia at various times after surgery. The level of VIP-like immunoreactivity (IR) is increased at 2 days, reaches a peak at 6 days, and then declines by 14 days to approximately half its peak value. The level of SP-IR also increases 2 days after axotomy, but returns to control values by day 6. The increase in SP-IR is accompanied by an increase in beta-preprotachykinin mRNA, suggesting that the elevation in SP content is due, at least in part, to enhanced peptide synthesis. Immunocytochemical localization of SP-IR revealed the presence of immunoreactive principal neurons in axotomized, but not in sham-operated ganglia. Similarities in the regulation of these two neuropeptides were also investigated in organ culture by examining the effects of dexamethasone and interleukin-1 beta on VIP content, since the former has been shown to prevent the increase in SP in culture, while the latter has been found to enhance this increase (Kessler, Adler, Bell, et al., 1983, Neuroscience 9:309-321; Freidin and Kessler, 1991, Proc. Natl. Acad. Sci. USA 88:3200-3203; Hart, Shadiack, and Jonakait, 1991, J. Neurosci. Res. 29:282-291). As with SP expression, dexamethasone reduces the increase in VIP expression, while interleukin-1 beta increases it. Thus, both in vivo and in vitro, similar changes in VIP and SP expression are observed following a number of experimental manipulations, suggesting that expression of the two peptides is regulated by qualitatively similar mechanisms in sympathetic neurons.

Animals↗
PubMed1993

Leukemia inhibitory factor mediates an injury response but not a target-directed developmental transmitter switch in sympathetic neurons.

Leukemia inhibitory factor (LIF; also known as cholinergic differentiation factor) is a multifunctional cytokine that affects neurons, as well as many other cell types. To examine its neuronal functions in vivo, we have used LIF-deficient mice. In culture, LIF alters the transmitter phenotype of sympathetic neurons, inducing cholinergic function, reducing noradrenergic function, and altering neuropeptide expression. In vivo, a noradrenergic to cholinergic switch occurs in the developing sweat gland innervation, and changes in neuropeptide phenotype occur in axotomized adult ganglia. We find that the gland innervation of LIF-deficient mice is indistinguishable from normal. In contrast, neuropeptide induction in ganglia cultured as explants or axotomized in situ is significantly suppressed in LIF-deficient mice. Thus, LIF plays a role in transmitter changes induced by axotomy but not by developmental interactions with sweat glands.

Animals↗
PubMed1992

Is the vasoactive intestinal peptide-like immunoreactivity in the rat pineal gland present in fibers originating in the superior cervical ganglion?

Serotonin N-acetyltransferase is regulated in the rat pineal gland by the gland's innervation from the superior cervical ganglion. Norepinephrine has been viewed as the sole transmitter involved in this trans-synaptic regulation; however, a possible role for vasoactive intestinal peptide (VIP) has recently emerged. VIP-like immunoreactivity was extracted from rat pineal glands and shown to co-elute on reverse-phase liquid chromatography with authentic VIP. The level of VIP-like immunoreactivity in the gland was unaffected by prior sympathetic denervation, though its level of neuropeptide Y-like immunoreactivity decreased by 85%. The results indicate that VIP and norepinephrine are not colocalized in sympathetic neurons in the pineal gland and raise questions as to the physiological role of VIP in regulation of pineal function in vivo.

Animals↗
PubMed1992

Phenotypic plasticity in adult sympathetic neurons: changes in neuropeptide expression in organ culture.

Vasoactive intestinal peptide (VIP)-like immunoreactivity is present at low levels in the superior cervical ganglion of the adult rat, where immunostained neural processes, but only an occasional immunostained cell body, are found. However, when ganglia are maintained for 24 or 48 hr in organ culture, their content of VIP-like immunoreactivity increases 6- or 31-fold, respectively. When examined at 24 hr, the increase in VIP-like immunoreactivity is totally blocked by an inhibitor of RNA or protein synthesis. Many neuronal cell bodies and processes with immunoreactivity for VIP and the related peptide histidine isoleucine amide (PHI) are seen in cultured ganglia. In addition, VIP/PHI mRNA is abundant in cultured ganglia but only barely detectable in ganglia prior to culture. Under the same culture conditions, neuropeptide Y-like immunoreactivity increases to a small extent, and tyrosine hydroxylase activity and total ganglion protein remain unchanged. These results support the idea that adult sympathetic neurons exhibit plasticity in neuropeptide expression and that this plasticity, in the case of VIP, depends on changes in gene expression.

Age Factors↗
PubMed1992

Depolarization increases vasoactive intestinal peptide- and substance P-like immunoreactivities in cultured neonatal and adult sympathetic neurons.

Depolarization has been shown to alter the biosynthesis of a number of neurotransmitters and neuromodulators. In the rat superior cervical ganglion (SCG), for example, depolarization has been reported to increase catecholamine biosynthesis and to decrease the level of substance P. We have recently found that, although the level of vasoactive intestinal peptide (VIP)-like immunoreactivity (IR) is normally low in the SCG, it increases significantly 48 hr after adult ganglia are deafferented in situ or placed in organ culture. Both manipulations decrease electrical activity of postganglionic neurons. To determine whether the increases in ganglionic VIP-IR could be a consequence of decreased depolarization of sympathetic neurons, the effect of depolarization on the expression of VIP-IR was examined in organ cultures of neonatal and adult SCG. Depolarization with elevated K+ (30 mM) or veratridine (1.5 microM) amplified, rather than blocked, the increases in VIP-IR content seen after 24 hr. Further, it increased the number of detectable VIP-IR neuronal cell bodies and processes. The stimulatory effects of veratridine were prevented by TTX. Since similar changes in expression of VIP-IR were evident in dissociated cell cultures of the SCG, cell-cell interactions requiring intact ganglionic architecture are not necessary for altered peptide expression. Elevating the concentration of Mg2+ blocked the ability of K+ and veratridine to increase VIP-IR in dissociated cell culture, raising the possibility that the effects of depolarization on VIP-IR are mediated by increased Ca2+ entry. The depolarizing conditions that increased VIP-IR also increased substance P-IR. While higher concentrations of veratridine (50 microM) blocked the elevation of both VIP- and substance P-IR induced by explantation, they produced significant neuronal death. Since depolarization with either 30 mM KCl or 1.5 microM veratridine increases expression of VIP-IR in neonatal and adult ganglia, decreased depolarization is unlikely to cause the increases in VIP- and substance P-IR that occur in culture. Furthermore, our data raise the possibility that sympathetic nerve activity in vivo can increase expression of these peptides.

Animals↗
PubMed1991

Distribution of vasoactive intestinal peptide- and peptide histidine isoleucine amide-like immunoreactive neurons and fibers in the thoracic spinal cord of the rat.

The distributions of vasoactive intestinal peptide (VIP)- and peptide histidine isoleucine amide (PHI)-immunoreactivities (IR) in the thoracic spinal cord of the rat are described. VIP- and PHI-IR were present in cells and fibers in the lateral spinal nucleus, lamina VII, nucleus proprius, substantia gelatinosa, intermediolateral cell column, and the area around the central canal. The functions of these peptides in the thoracic spinal cord are not known; however, their locations suggest that they are involved in sensory and autonomic functions, among others.

Animals↗
PubMed1991

Functional recovery and collateral neuronal sprouting examined in young and aged rats following a partial neural lesion.

The rat pineal gland was chosen as a model system to study how aging affects the capacity of surviving neurons to compensate for partial destruction of a neural pathway. The pineal gland receives bilateral overlapping sympathetic innervation from the two internal carotid nerves, whose activity regulates several aspects of pineal metabolism in a circadian fashion. The most dramatic of these is the marked nighttime increase in the activity of N-acetyltransferase, the rate-limiting enzyme in melatonin synthesis. These features allow for the pineal gland to be used as a model system for studies on neuronal plasticity, since it is possible to create specific partial neural lesions and to evaluate functional recovery subsequently at the cellular level. We examined the activity of N-acetyltransferase and the content of melatonin in the pineal gland as indices of pineal function at various time points after unilateral surgical denervation (lesion of one of the two internal carotid nerves) in 4-month-(young) and 25-month-old (aged) rats. At both ages, the nighttime levels of the two parameters were significantly lower 8 h after this lesion than in sham-operated animals of the same age, indicating impaired function. When examined at later time points (i.e., 1.5 and 10 days after this lesion), both young and aged animals exhibited full recovery in these two parameters. Measurement of specific neuronal uptake of [3H]norepinephrine was utilized as an index of the number of sympathetic varicosities innervating the pineal gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Evidence that some preganglionic sympathetic neurons in the rat contain vasoactive intestinal peptide- or peptide histidine isoleucine amide-like immunoreactivities.

Physiological studies have established that preganglionic sympathetic nerve fibers innervating the rat superior cervical ganglion release a second transmitter, in addition to acetylcholine. Based on pharmacological and histochemical investigations, possible candidates for this non-cholinergic neurotransmitter include vasoactive intestinal peptide and peptide histidine isoleucine amide. For example, previous immunohistochemical studies have demonstrated that antisera raised against both of these peptides stain neural processes in the rat preganglionic cervical sympathetic trunk and in the superior cervical ganglion. In the present study, it was found that, when the cervical sympathetic trunk was ligated, vasoactive intestinal peptide- and peptide histidine isoleucine amide-like immunoreactivities built up on both sides of the ligature. In addition, examination of the thoracic spinal cord in colchicine-treated animals revealed vasoactive intestinal peptide- and peptide histidine isoleucine amide-like immunoreactivies in neuronal cell bodies in the intermediolateral cell column and in the region of the lateral funiculus adjacent to it. In a second group of animals in which retrograde tracing techniques were used, these two regions of the spinal cord were shown to contain most of the cell bodies of the preganglionic neurons that project to the superior cervical ganglion. Smaller numbers of retrogradely labeled neurons were found dorsal to the central canal and in the nucleus intercalatus. When either vasoactive intestinal peptide- or peptide histidine isoleucine amide-like immunostaining and retrograde labeling were examined in the same animals, double-labeled neurons were found in the intermediolateral cell column and in the lateral funiculus. These data demonstrate that vasoactive intestinal peptide- and peptide histidine amide-like immunoreactivities are present in certain of the preganglionic neurons that project to the superior cervical ganglion, supporting the hypothesis that vasoactive intestinal peptide and peptide histidine isoleucine amide are released in the ganglion when these preganglionic neurons are activated.

Animals↗
PubMed1991

Effects of peptides of the secretin-glucagon family and cyclic nucleotides on tyrosine hydroxylase activity in sympathetic nerve endings.

Previous studies have shown that certain peptides of the secretin-glucagon family stimulate tyrosine hydroxylase activity in sympathetic neurons of the superior cervical ganglion and three of its end organs, i.e., the iris, pineal gland, and submaxillary gland. To determine whether a similar regulation occurs in other sympathetic neurons, the effects of two of these peptides, secretin and vasoactive intestinal peptide, were examined in the right cardiac ventricle of the rat, a tissue innervated primarily by the middle and inferior cervical ganglia. Both peptides stimulated tyrosine hydroxylase activity, measured in situ, in this tissue. In addition, several second messenger systems were investigated as possible mediators of this peptidergic stimulation of tyrosine hydroxylase activity in autonomic end organs. 8-Bromoadenosine 3',5'-cyclic monophosphate and forskolin elevated tyrosine hydroxylase activity in slices of both the right ventricle and the submaxillary gland. 8-Bromoguanosine 3',5'-cyclic monophosphate also stimulated tyrosine hydroxylase activity in both tissues, whereas nitroprusside stimulated activity only in the submaxillary slices. Furthermore, the phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine and/or Ro 20-1724 potentiated the stimulation by secretin, as well as the stimulations by forskolin and nitroprusside. Phorbol 12,13-dibutyrate also stimulated tyrosine hydroxylase activity in cardiac and submaxillary slices; however, no potentiation of these effects was seen following addition of either phosphodiesterase inhibitor. These data, taken together with those of previous studies, suggest a role for a cyclic nucleotide, probably adenosine 3',5'-cyclic monophosphate, in the peptidergic stimulation of tyrosine hydroxylase activity in sympathetic nerve terminals.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Omega-conotoxin inhibits the acute activation of tyrosine hydroxylase and the stimulation of norepinephrine release by potassium depolarization of sympathetic nerve endings.

Increased Ca2+ influx serves as a signal that initiates multiple biochemical and physiological events in neurons following depolarization. The most widely studied of these phenomena is the release of neurotransmitters. In sympathetic neurons, depolarization also increases the rate of synthesis of the transmitter norepinephrine (NE), via an activation of the enzyme tyrosine hydroxylase (TH), and this effect also seems to involve Ca2+ entry. We have examined whether the mechanism of Ca2+ entry relevant to TH activation is via voltage-sensitive Ca2+ channels and, if so, whether the type of Ca2+ channel involved is the same as that involved in the stimulation of NE release. We have investigated the isolated rat iris, allowing us to examine transmitter biosynthesis and release in sympathetic nerve terminals in the absence of sympathetic cell bodies and dendrites. Potassium depolarization produced a three- to fivefold increase in TH activity and an approximately 100-fold increase in NE release. Both effects were dependent on Ca2+ being present in the extracellular medium, and both were inhibited by omega-conotoxin (1 microM), which inhibits N-type voltage-sensitive Ca2+ channels. In contrast, the dihydropyridine nimodipine (1-3 microM), which blocks L-type Ca2+ channels, had no effect on either measure. These data support the hypothesis that increases in NE biosynthesis and release in sympathetic nerve terminals during periods of depolarization are both initiated by an influx of Ca2+ through voltage-sensitive Ca2+ channels and that a similar type of Ca2+ channel is involved in both processes.

Animals↗
PubMed1991

Vasoactive intestinal peptide stimulates catecholamine biosynthesis in isolated adrenal chromaffin cells: evidence for a cyclic AMP-dependent phosphorylation and activation of tyrosine hydroxylase.

Vasoactive intestinal peptide (VIP) increased catecholamine biosynthesis in bovine adrenal chromaffin cells by 50-200%. Six related peptides produced no effects. In addition, VIP increased tyrosine hydroxylase (TH) activity measured in gel-filtered supernatants prepared from homogenates of treated cells. The hypothesis that cyclic AMP is the second messenger involved in these effects of VIP was also evaluated. VIP led to an elevation of cyclic AMP levels, and this increase occurred over a similar concentration range and time course as the activation of TH and the increase in catecholamine biosynthesis. Each measure reached maximal levels at 10-20 microM VIP within 1 min and remained elevated for at least 16 min. These changes produced by VIP were paralleled by enhanced phosphorylation of TH, and this phosphorylation occurred on a single tryptic peptide that was the same peptide whose phosphorylation has been previously shown to be stimulated by forskolin. In contrast to VIP and forskolin, 12-O-tetradecanoylphorbol 13-acetate, a phorbol ester known to activate protein kinase C, increased the phosphorylation on a total of three tryptic peptides of TH. Our results indicate that VIP stimulates catecholamine biosynthesis in chromaffin cells through the phosphorylation and activation of TH and support the conclusion that a cyclic AMP-dependent phosphorylation of TH is responsible for these effects.

Adrenal Glands↗