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D L McNeill

Publications and source records attributed to D L McNeill.

At least 19 recordsLinked to original sources
PubMed1995

Spinal projection neurons to the laterodorsal pontine tegmental nucleus: relationship to preganglionic neurons and nitric oxide synthase.

The region of the rat sacral parasympathetic nucleus (SPN) contains distinct subpopulations of neurons that project supraspinally or are preganglionic neurons. Some preganglionic neurons in the SPN serve as the motor outflow for urinary bladder contraction; other neurons in the SPN project to regions of the rostral pons that subserve micturition reflexes. Previous studies utilizing immunohistochemistry or staining for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) have demonstrated that numerous neurons in the SPN contain nitric oxide synthase (NOS), the enzyme for nitric oxide synthesis. Thus, the objectives of this study were to determine 1) the distribution of neurons in the region of the SPN that project to the laterodorsal tegmentum (LDT) of the pons, 2) whether spinal neurons projecting to a peripheral autonomic ganglion also project to the LDT, and 3) whether NOS or NADPH-d is present in LDT projection neurons. Preganglionic neurons were identified by injecting the retrograde tracer fluorogold (FG) into the major pelvic ganglion (MPG). Supraspinally projecting neurons were identified by injecting the retrograde tracer fast blue (FB) into the LDT. Numerous FB-labeled neurons were present in the ipsi- and contralateral SPN and were immediately dorsal to FG-labeled preganglionic neurons. Neurons containing both tracers were not observed. Approximately 20% of preganglionic neurons, but no LDT projection neurons, were reactive for NOS and NADPH-d. These data suggest that the region of the SPN is a site for distinct subpopulations of neurons that project to the LDT and to the MPG and that NOS is contained in some preganglionic neurons, but is not a marker for LDT projection neurons.

Amidines↗
PubMed1995

Nitric oxide nerves in the uterus are parasympathetic, sensory, and contain neuropeptides.

Nitric oxide (NO) is synthesized in neurons and is a potent relaxor of vascular and nonvascular smooth muscle. The uterus contains abundant NO-synthesizing nerves which could be autonomic and/or sensory. This study was undertaken to determine: 1) the source(s) of NO-synthesizing nerves in the rat uterus and 2) what other neuropeptides or transmitter markers might coexist with NO in these nerves. Retrograde axonal tracing, utilizing Fluorogold injected into the uterine cervix, was employed for identifying sources of uterine-projecting neurons. NO-synthesizing nerves were visualized by staining for nicotinamide adenine dinucleotide phosphate (reduced)-diaphorase (NADPH-d) and immunostaining with an antibody against neuronal/type I NO synthase (NOS). NADPH-d-positive perikarya and terminal fibers were NOS-immunoreactive (-I). Some NOS-I/NADPH-d-positive nerves in the uterus are parasympathetic and originate from neurons in the pelvic paracervical ganglia (PG) and some are sensory and originate from neurons in thoracic, lumbar, and sacral dorsal root ganglia. No evidence for NOS-I/NADPH-d-positive sympathetic nerves in the uterus was obtained. Furthermore, double immunostaining revealed that in parasympathetic neurons, NOS-I/NADPH-d-reactivity coexists with vasoactive intestinal polypeptide, neuropeptide Y, and acetylcholinesterase and in sensory nerves, NOS-I/NADPH-d-reactivity coexists with calcitonin gene-related peptide and substance P. In addition, tyrosine hydroxylase(TH)-I neurons of the PG do not contain NOS-I/NADPH-d-reactivity, but some TH-I neurons are apposed by NOS-I varicosities. These results suggest NO-synthesizing nerves in the uterus are autonomic and sensory, and could play significant roles, possibly in conjunction with other putative transmitter agents, in the control of uterine myometrium and vasculature.

Amino Acid Oxidoreductases↗
PubMed1993

Light- and electron-microscopic study of synaptic connections in the paracervical ganglion of the female rat: special reference to calcitonin gene-related peptide-, galanin- and tachykinin (substance P and neurokinin A)-immunoreactive nerve fibers and terminals.

Nerve fibers and varicosities in the pelvic paracervical ganglia (PG) are immunoreactive for the neuropeptides calcitonin gene-related peptide, galanin, and the tachykinins substance P and neurokinin A. Many of these fibers and varicosities are capsaicin-sensitive, originate in dorsal root ganglia and, thus, are considered to be primary afferent fibers. Numerous immunoreactive varicosities are pericellular to principal neurons in the PG. The present study examines the ultrastructure of calcitonin gene-related peptide-, galanin-, substance P-, and neurokinin A-immunoreactive nerve fibers and varicosities in the ganglia to determine their relationships to principal neurons and their synaptic connectivity. Paracervical ganglia of female rats were processed for light-microscopic immunohistochemistry using antisera against synapsin I, as a nerve terminal marker, and microtubule-associated protein-2 to define soma and dendrites. The rationale for performing this co-immunohistochemical analysis was to reveal the relationship between nerve endings and principal neurons. Synapsin I endings were predominantly axosomatic with fewer being axodendritic. Other ganglia were processed for electron-microscopic immunohistochemistry using both standard immunogold and peroxidase-anti-peroxidase procedures. Unmyelinated fibers and varicosities immunoreactive for calcitonin gene-related peptide, galanin, and the tachykinins were routinely observed in the interstitium between neuron somas. Numerous immunoreactive axon profiles were present in small groups that were ensheathed by Schwann cells. Immunoreactive fibers and varicosities were also observed within the satellite-cell sheath of the neuron soma and often intimately associated with the membrane of the soma, somal protrusions, or with the proximal part of a dendrite. Membrane specializations, indicative of synaptic contacts, between the fibers and the principal neurons were observed. It is suggested that these peptide-immunoreactive sensory fibers and varicosities are involved in regulation of activity in the PG.

Animals↗
PubMed1992

Distribution of NADPH-diaphorase-positive nerves in the uterine cervix and neurons in dorsal root and paracervical ganglia of the female rat.

Nitric oxide synthase (NOS) was selectively stained in nerve fibers of the uterine cervix and neurons of the paracervical (PG) and dorsal root ganglia (DRG) by NADPH diaphorase histochemistry. In the cervix, numerous NADPH-diaphorase-positive nerve fibers were observed in the myometrium, endometrium and around arteries. In addition, a subpopulation of neurons within ganglia that innervate the cervix, i.e., the PG and DRG, were NADPH-diaphorase positive; thus the fibers in the cervix could be sensory and/or autonomic. NADPH-diaphorase/NOS localization identifies sites where nitric oxide (NO) can be synthesized. Since NO relaxes vascular and nonvascular smooth muscle, the prevalence and anatomical localization of NADPH-diaphorase-positive fibers suggest that they could influence functions of the uterine cervix.

Amino Acid Oxidoreductases↗
PubMed1992

Origin and distribution of NADPH-diaphorase-positive neurons and fibers innervating the urinary bladder of the rat.

Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry was utilized to localize nitric oxide synthase (NOS), and thus sites where nitric oxide (NO) can be synthesized, within peripheral nervous system perikarya and fibers. Recent studies suggest that NO relaxes vascular and non-vascular smooth muscle. In this study, the origin and distribution of NADPH-diaphorase perikarya and fibers in the rat urinary bladder were examined. Results suggest that a small number of NADPH-diaphorase-positive perikarya are present within the bladder wall and within adjacent small ganglia. In addition, NADPH-diaphorase-positive nerve fibers were observed in the adventitial and muscular layers, subjacent to the urothelium and as perivascular fibers. After injection of the retrograde tracer fluorogold (FG) into the bladder wall, numerous FG-labeled perikarya in the major pelvic ganglia and the T13-L2, L6 and S1 dorsal root ganglia were NADPH-diaphorase positive. However, none of the FG-labeled perikarya in the inferior mesenteric ganglia were NADPH-diaphorase positive. The prevalence of NADPH-diaphorase-positive perikarya and fibers suggests that NO may serve a role in bladder function.

Amino Acid Oxidoreductases↗
PubMed1992

Effects of spinal cord transection and MK-801 on CGRP immunostaining in the rat urinary bladder.

Numerous studies have demonstrated that lesions in the CNS can alter the density of sensory nerve processes in peripheral organs. In the present study, rat spinal cords were transected at the second lumbar segmental level and the density of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the urinary bladder was examined. Additional rats had spinal cord transections followed by 12 days of treatment with the N-methyl-D-aspartate receptor antagonist, MK-801. In the bladders of control rats, CGRP-immunoreactive fibers were present as thick nerve trunks, perivascular plexi, and a fine meshwork of varicose nerve fibers. Twelve days following a spinal cord transection, the density of CGRP-immunoreactive nerve fibers was markedly reduced; occasional fibers appeared primarily as nonvaricose fine fibers. In bladders from rats receiving a spinal cord transection and MK-801 treatment, CGRP-immunoreactive fibers were abundantly distributed throughout the detrusor muscle; these fibers exhibited numerous varicosities as well as some enlarged terminal varicosities. These data demonstrate that (i) an upper motor neuron-type lesion markedly decreases the density of CGRP-immunoreactive peripheral afferent nerve processes and (ii) following a spinal cord transection, MK-801 appears to enhance the density of CGRP immunostaining in the bladder.

Animals↗
PubMed1992

CGRP-immunoreactive primary afferent nerve fibers in the rat urinary bladder: effects of dorsal rhizotomy and MK-801.

A transection lesion of the suprasacral spinal cord results in a decreased density of calcitonin gene-related peptide (CGRP)-immunoreactive (I) primary afferent nerve fibers in the rat urinary bladder. The fiber density can be restored by postsurgical treatment with the N-methyl-D-aspartate receptor antagonist MK-801. We are attempting to determine the level of the primary afferent neuron at which MK-801 might have a restorative effect on CGRP immunostaining. Thus, the purpose of this study was to determine if MK-801 had a similar restorative effect on immunostaining for CGRP in bladder nerves after a direct lesion of the sacral afferent system, i.e., rhizotomy of the L6 and S1 dorsal roots. To assess the effect of the lesion, the mean length and number of bladder CGRP-I nerve fibers, as well as the number of CGRP-I perikarya in the L6 and S1 dorsal root ganglia (DRG), were measured following bilateral L6 and S1 dorsal rhizotomies. Both the mean length and the numbers of CGRP-I bladder fibers were significantly decreased by the lesion. However, the number of CGRP-I primary afferent perikarya in the L6 and S1 DRG was unchanged from control values. Rats which received rhizotomies and subsequent treatment with MK-801 did not exhibit restoration of the density of CGRP-I bladder fibers nor an alteration in the number of CGRP-I primary afferent perikarya. These data suggest that MK-801-induced restoration of bladder CGRP-I primary afferent nerve fibers may rely on an intact central process.

Afferent Pathways↗
PubMed1991

Parathyroid hormone-related protein inhibits stimulated uterine contraction in vitro.

The effect of parathyroid hormone-related protein (PTHrP) fragments 1-34, 38-64, and 67-86 on acetylcholine-stimulated rat uterine contraction was examined in vitro. In addition, the possibility that PTHrP-(38-64) or (67-86) influenced relaxation caused by PTHrP-(1-34) was also investigated. Contraction of uterine horns was stimulated with 10(-6) or 10(-5) M acetylcholine. PTHrP-(1-34) reduced the magnitude of acetylcholine-stimulated uterine contraction. This effect was dose related over a concentration range of 10(-9)-10(-6) M. Neither PTHrP-(38-64) or PTHrP-(67-86) at concentrations of 10(-8)-10(-6) M affected uterine contraction stimulated by 10(-6) M acetylcholine. These fragments did not affect the relaxation caused by 10(-7) M PTHrP-(1-34). These results demonstrate that (1) PTHrP-(1-34) at 10(-6) M influences contraction of the rat myometrium and (2) the muscle relaxant activity of PTHrP is associated with the first 34 N-terminal amino acids.

Acetylcholine↗
PubMed1991

Intraspinal sprouting of calcitonin gene-related peptide containing primary afferents after deafferentation in the rat.

The occurrence of sprouting in the spinal cord in response to denervation has been a subject of debate. To test for sprouting of primary afferent fibers after denervation, rats were unilaterally deafferented for 35 days (chronic side) by dorsal rhizotomies performed from T2 to T8 and T10 to L5, thus isolating or sparing the T9 root. The contralateral T9 root was spared by a similar surgery 5 days (acute side) prior to sacrifice. The survival time on the chronic side presumably allows intraspinal sprouting of T9 primary afferents to occur whereas the time on the acute side does not. To test for sprouting of primary afferents, it is necessary to identify these nerve processes. Calcitonin gene-related peptide (CGRP) immunoreactivity has been localized to a subpopulation of primary afferent nerve processes and their terminals within the dorsal horn. Therefore, immunohistochemical methods were used to determine the distribution of CGRP immunoreactivity in laminae I and II on both sides of the spinal cord. Using image analysis, there was an increase of 153 to 704% in the density of CGRP immunoreaction product on the chronic side compared to the acute side in the spared segment. This difference is statistically significant. Furthermore, the increased density on the chronic side extended two segments cranial and two segments caudal to the spared root segment. No difference was found in the laminar distribution between sides. These data support the hypothesis of primary afferent sprouting following spinal cord denervation.

Animals↗
PubMed1991

Origin of galanin-immunoreactive nerve fibers in the rat paracervical autonomic ganglia and uterine cervix.

Retrograde axonal tracing with fluorogold in conjunction with immunohistochemistry was used to examine the source of galanin-immunoreactive nerve fibers in the paracervical ganglia and uterine cervix of the female rat. Immunohistochemistry revealed galanin-immunoreactive neuron somata in lumbosacral dorsal root ganglia and around the central canal of the lumbosacral spinal cord (lamina X). Injection of fluorogold into the paracervical ganglia resulted in labelled cells in dorsal root ganglia and the sacral parasympathetic nucleus of the spinal cord; but fluorogold-labelled, galanin-immunoreactive cells were found only in dorsal root ganglia. Injection of the tracer in the cervix resulted in labelled cells in the paracervical ganglia and dorsal root ganglia; however, fluorogold-labelled, galanin-immunoreactive cells were again evident only in dorsal root ganglia. It is suggested that the galanin-immunoreactive nerve fibers and varicosities in the paracervical ganglia and uterine cervix are sensory fibers from spinal dorsal root ganglia. The galanin-immunoreactive varicosities in the ganglia could play a role in the modulation of pelvic visceral activity, while those in the musculature of the cervix could influence contractility.

Animals↗
PubMed1991

Projection of nodose ganglion cells to the upper cervical spinal cord in the rat.

Afferent fibers mediating pain from myocardial ischemia classically are believed to travel in sympathetic nerves to enter the thoracic spinal cord. After sympathectomies, angina pectoris still may radiate to the neck and inferior jaw. Sensory fibers from those regions are thought to enter the central nervous system through upper spinal cord segments. We postulated that axons from nodose ganglion cells might project to cervical cord segments. The purpose of this study was to determine the density and pathway of vagal afferent innervation to the upper cervical spinal cord. Following an injection of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the upper cervical spinal cord, approximately 5.8% of cells in the nodose ganglion contained reaction product. Cervical vagotomy did not diminish the density of WGA-HRP labeled cells in the nodose ganglion. However, a spinal cord hemisection cranial to the injection site eliminated labeling of nodose cells. These data indicate that a portion of vagal afferent neurons project from the nodose ganglion to the upper cervical spinal cord. In addition, vagal afferent fibers reach the spinal cord via a central route rather than through dorsal root ganglia.

Animals↗
PubMed1991

Effects of MK-801 on rat primary afferent neurons and fibers.

Recent evidence suggests that glutamate and its N-methyl-D-aspartate (NMDA) receptor may participate in regulating neurite morphology and peptide expression. A previous study from this laboratory showed that treatment with the NMDA receptor antagonist, MK-801, induced an apparent increase in the density of calcitonin gene-related peptide (CGRP)-immunoreactive primary afferent fibers in the dorsal spinal cord of the rat. The present study was undertaken to extend this work by: 1) quantifying the MK-801-induced increase in CGRP immunostaining in the dorsal grey commissure/medial dorsal horn region and 2) examining the effect of MK-801 on the number of CGRP-immunoreactive primary afferent cell bodies in lumbar dorsal root ganglia. Following 7 days of MK-801 treatment, a significant increase (p less than 0.001) in CGRP immunostaining was observed in the dorsal grey commissure/medial dorsal horn. However, after MK-801 treatment, no significant difference was noted in the numbers of CGRP-immunoreactive primary afferent cell bodies in dorsal root ganglia. These data suggest that MK-801 produces significant alterations in the intraspinal projection of CGRP-immunoreactive fibers without inducing immunocytochemically detectable CGRP within a new population of primary afferent neurons.

Afferent Pathways↗
PubMed1991

Effects of ethanol exposure on myelination and axon numbers in the L2 dorsal root of the neonatal rat.

Previous studies have demonstrated that exposure to ethanol during development delays the rate at which axons in certain central nervous system tracts acquire myelin. This delay appears to be related to an alteration in oligodendrocyte function and not to an aberrancy in axon size or number. The present study was designed to determine if alterations similar to those observed in the central nervous system also occur in peripheral nerves, specifically the L2 dorsal root. Dams were fed either an ethanol-containing or control liquid diet 2 weeks prior to pregnancy and throughout gestation. The pups born to the pregnant dams were artificially reared from postnatal day (PD) 4 to PD 10 on a similar ethanol-containing or control diet. The pups were sacrificed on PD 10, L2 dorsal roots removed and processed for electron microscopy. The numbers of axons in various states of myelination were quantified. No difference was observed in the number of unmyelinated axons in the L2 dorsal roots from ethanol-exposed and control pups. In roots from ethanol-exposed pups, there was a significant decrease in the number of axons possessing myelin arranged in compact lamellae, but a significant increase in the number of axons surrounded by myelin lamellae in which the Schwann cell cytoplasm had not yet been extruded (noncompact). However, when the number of axons possessing noncompact myelin and a compact myelin sheath were summed, no significant difference was observed. These data suggest that the delay in myelination following ethanol exposure may be a ubiquitous phenomenon throughout the nervous system.

Abnormalities, Drug-Induced↗
PubMed1990

MK-801-induced sprouting by CGRP immunoreactive primary afferent fibers in the dorsal spinal cord of the rat.

In the present study, rats received daily injections of the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, over 30 consecutive days. The effects of MK-801 on the distribution of calcitonin gene-related peptide (CGRP)-immunoreactive fibers in the dorsal spinal cord of the rat were subsequently examined. In addition to the normal immunostaining pattern in laminae I, II and lateral V, a dense network of CGRP-immunoreactive fibers was observed along the medial border of the dorsal horn and within the dorsal grey commissure. This marked increase in immunoreactivity was virtually eliminated following dorsal rhizotomy. These observations suggest that MK-801 induces intraspinal sprouting by CGRP immunoreactive primary afferent fibers in vivo.

Afferent Pathways↗
PubMed1990

Denervation-induced intraspinal synaptogenesis of calcitonin gene-related peptide containing primary afferent terminals.

The purpose of the present study is to provide evidence that chronic spinal denervation leads to an increase in numbers of synaptic terminals from a specific population of primary afferent fibers. Rats were unilaterally deafferented for 35 days (chronic denervation) by dorsal rhizotomies performed from T2 to T8 and T10 to L5, which isolates or spares the T9 root. The contralateral T9 root was spared by similar surgery 5 days (acute denervation) prior to sacrifice. The survival time on the chronic side presumably allows sprouting of T9 primary afferents to occur, whereas the time on the acute side does not. The terminals were labeled with calcitonin gene-related peptide (CGRP), which is a compound that labels a specific population of primary afferent fibers and terminals, and stereological methods were used to determine the numbers of immunolabeled terminals in laminae I and IIo on the chronic and acute sides of the T9 spinal cord. The findings are that the chronic side had approximately twice as many terminals as the acute side. This difference is statistically significant. These findings are compatible with the hypothesis that chronic denervation leads to synaptogenesis from surviving primary afferent fibers.

Animals↗
PubMed1989

Ascending unmyelinated primary afferent fibers in the dorsal funiculus.

The primary purpose of the present study is to obtain evidence as to the destination of the recently discovered unmyelinated primary afferent fibers in the mammalian dorsal funiculus. To do this rat dorsal roots were transected unilaterally from segments T8 or T9 caudally, and the numbers of axons were determined in the C3 fasciculus gracilis in normal animals and from both sides of the rhizotomied animals. In addition, C3 fasciculus gracilis counts were done in animals that had complete T6 or T10 spinal transections. The data indicate that there is an 80% loss of unmyelinated axons ipsilaterally and a 60% loss contralaterally in the fasciculus gracilis of the rhizotomied animals. These findings are interpreted as indicating that a significant fraction of the unmyelinated fibers in the fasciculus gracilis ascend, presumably to the nucleus gracilis in the brain stem, and also that a significant number of these fibers branch. We also provide evidence for contralateral myelinated primary afferent fiber projection in the fasciculus gracilis and show that the myelinated primary afferent fibers seem to be a more diverse population than the unmyelinated primary afferent fibers in the C3 fasciculus gracilis.

Animals↗
PubMed1989

Aspartate immunoreactive axons in normal rat L4 dorsal roots.

The present study demonstrates that approximately 15% of the unmyelinated axons and 4% of the myelinated axons in the rat L4 dorsal root are immunostained for the excitatory amino acid aspartate. Thus these primary afferent axons contain enough of the antigen to be labeled. This is the first report that high concentrations of aspartate characterize a subpopulation of dorsal root axons. This allows the suggestion that aspartate is a candidate transmitter for primary afferent neurons. We emphasize that these axons are demonstrated in otherwise normal animals so that changes in percentages of labeled axons in response to various stimuli are not complicated by manipulations usually necessary to demonstrate immunoreactive compounds in the cell body.

Animals↗