Kenneth E Miller

Kenneth E Miller
Oklahoma State University - Center for Health Sciences · Anatomy and Cell Biology

Ph.D.

About

66
Publications
2,688
Reads
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1,561
Citations
Introduction
Skills and Expertise
Additional affiliations
July 2002 - present
January 1993 - July 2002
July 1987 - December 1988
University of Miami
Position
  • Research Assistant

Publications

Publications (66)
Article
Easy-to-use and inexpensive techniques are needed to determine the site-specific production of inflammatory mediators and neurotrophins during skin injury, inflammation, and/or sensitization. The goal of this study is to describe an epidermal-dermal separation protocol using thermolysin, a proteinase that is active at 4 °C. To illustrate this proce...
Article
Pseudo-unipolar cell bodies of somatosensory primary neurons are located in the dorsal root ganglia (DRG). The somatic and peripheral domains of DRG neurons are often studied in sensory pain research to understand molecular mechanisms involved in the activation of pain and maintenance of inflammation. Adjuvant-induced arthritis (AIA) is an inflamma...
Article
Immunohistochemistry (IHC) is a valuable tool in clinical and biological research for evaluating proteins and other antigens in spatially bound tissue. In neuroinflammatory pain research, primary afferent neurons of the dorsal root ganglion (DRG) are studied to understand molecular signaling mechanisms involved in nociception (pain) and inflammatio...
Article
Full-text available
Prior research has found that cognitive benefits of physical exercise and brain health in older adults may be enhanced when mental exercise is interactive simultaneously, as in exergaming. It is unclear whether the cognitive benefit can be maximized by increasing the degree of mental challenge during exercise. This randomized clinical trial (RCT),...
Poster
Nerve growth factor (NGF) is a molecule which regulates the maturation of developing sensory neurons in the peripheral nervous system (PNS) and acts as neurotrophin for a subset of nociceptive (pain-producing) sensory neurons. NGF has two known receptors, TrkA and p75NTR. The peripheral terminals of the primary afferents keep constant communication...
Article
Full-text available
The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the pr...
Article
Full-text available
Glutamate is a neurotransmitter used at both the peripheral and central terminals of nociceptive primary sensory neurons, yet little is known concerning regulation of glutamate metabolism during peripheral inflammation. Glutaminase (GLS) is an enzyme of the glutamate-glutamine cycle that converts glutamine into glutamate for neurotransmission and i...
Article
Glutamate is an excitatory neurotransmitter, produced by its synthetic enzyme, glutaminase (GLS), and packaged by vesicular transporters (VGluT2) into synaptic vesicles. Primary sensory peripheral nerve and spinal synaptic terminals release glutamate during nociceptive (pain) signaling. In post-incisional and inflammation models in rats, GLS and VG...
Article
Glutamate is an excitatory neurotransmitter, released by primary sensory peripheral nerve and spinal synaptic terminals during nociceptive (pain) signaling. The primary source of neurotransmitter, glutamate, is provided from its synthetic enzyme, glutaminase (GLS). Neurotransmitter glutamate is packaged into synaptic vesicles in nociceptive neurons...
Article
Full-text available
Many medial septal neurons of the basal forebrain are dependent on nerve growth factor (NGF) from the hippocampus for survival and maintenance of a cholinergic phenotype. When deprived of their source of NGF by axotomy, medial septal neuronal cell bodies atrophy and lose their cholinergic markers. This is similar to what is observed in the basal fo...
Article
Full-text available
Following inflammation, primary sensory neurons in the dorsal root ganglion (DRG) alter the production of several proteins. Most DRG neurons are glutamatergic, using glutaminase as the enzyme for glutamate production, but little is known about glutaminase following inflammation. In the present study, adjuvant-induced arthritis (AIA) was produced in...
Article
Full-text available
Stereotaxic administration of L-cysteine (CySH) into the rat substantia nigra pars compacta (SNC) evokes a dose-dependent fall of striatal levels of dopamine. This, together with decreased tyrosine hydroxylase immunoreactivity in the striatum and SNcand decreased nigral staining for Niss1 substance indicate that CySH is a dopaminergic neurotoxin. T...
Article
Nerve growth factor (NGF) antagonism has long been proposed as a chronic pain treatment. In 2010, the FDA suspended clinical trials using tanezumab, a humanized monoclonal anti-NGF antibody, to treat osteoarthritis due to worsening joint damage in 16 patients. Increased physical activity in the absence of acute pain which normally prevents self-har...
Article
In addition to using glutamate as a neurotransmitter at central synapses, many primary sensory neurons release glutamate from peripheral terminals. Primary sensory neurons with cell bodies in dorsal root or trigeminal ganglia produce glutaminase, the synthetic enzyme for glutamate, and transport the enzyme in mitochondria to peripheral terminals. V...
Article
We have demonstrated the synthesis of insulin by neurons within the central nervous system in vivo and in vitro. We showed that neuronal insulin induces neuronal differentiation and axonal growth. In insulin type 1 and type 2 diabetes mellitus, one major complication is nervous system neuropathy. Lack of insulin has been postulated to be the cause...
Article
In inflamed tissue, the levels of the excitatory amino acid glutamate are increased. Glutamate sensitizes peripheral axons of primary afferent neurons during inflammation leading to decreased firing threshold and hyperexcitability. One proposed source of glutamate is the primary afferent. Antagonizing glutamate receptors on peripheral axons of prim...
Article
Full-text available
Most, if not all, dorsal root ganglion (DRG) neurons use the neurotransmitter glutamate. There are, however, conflicting reports of the percentages of DRG neurons that express glutaminase (GLS), the enzyme that synthesizes glutamate, ranging from 30% to 100% of DRG neurons. Defining DRG neuron populations by the expression of proteins like GLS, whi...
Article
We have shown recently that glial cells of the peripheral nervous system contain substrates and enzymes related to the glutamine cycle, e.g. glutamine, glutamine synthetase, and glutamate dehydrogenase (Miller et al., Brain Res 2002: 945: 202–11). The present study used immunohistochemistry to determine the cellular distribution of glutamine and gl...
Article
Full-text available
Dorsal root ganglia (DRG) neurons connect the spinal cord and uterine cervix, and are activated at parturition with subsequent stimulation of secondary neurons in the spinal dorsal horn and autonomic areas. Neuropeptide neurotransmitters and receptors have been studied in these areas, but amino acid transmitters, e.g., glutamate, an excitatory neur...
Article
The purpose of this study was to examine how upper thoracic spinal neurons responded to activation and desensitization of cardiac transient receptor potential vanilloid-1 (TRPV1)-containing afferent fibers. Extracellular potentials of single T3 spinal neurons were recorded in pentobarbital-anesthetized, paralyzed, and ventilated male rats. To activ...
Article
Complications of diabetes mellitus within the nervous system are peripheral and central neuropathy. In peripheral neuropathy, defects in neurofilament and microtubules have been demonstrated. In this study, we examined the effects of insulin deficiency within the brain in insulin knockout mice (I-/-). The I-/- exhibited hyperphosphorylation of tau,...
Article
A number of studies have implicated the interactions of the excitatory amino acid L-glutamate (Glu) with its ionotropic and metabotropic receptors as important components of the mechanism underlying the dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium [MPP(+)]. Furthermore, microdialysis experiments have demonstrated that perfusion of rela...
Article
beta-Arrestin-1 (betaArr1) plays a major role in the desensitization and internalization of G protein-coupled receptors. We previously localized betaArr1 in the sensory neurons of rat lumbar 4 and 5 dorsal root ganglia (DRG) and reported the predominant presence of betaArr1 in the small-diameter DRG neurons that are often implicated with nociceptio...
Article
Some evidence shows that the upper cervical spinal cord might play an important role in propriospinal processing as a sensory filter and modulator for visceral afferents. The aims of this study were to determine (1). the responses of C(1)-C(2) spinal neurons to gastric distension and (2). the relative contribution of vagal and spinal visceral affer...
Article
The purposes of this study were to examine responses of superficial (depth <300 microm) and deeper thoracic spinal neurons to chemical stimulation of cardiac afferents and effects of descending influences on these neurons. Extracellular potentials of single T(3)-T(4) neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male...
Article
Supporting glial cells of the peripheral nervous system include satellite cells of dorsal root ganglia and Schwann cells of peripheral nerves. In the central nervous system, glial cells contain enzymes related to the tricarboxylic acid and glutamine cycles: pyruvate carboxylase, glutamate dehydrogenase, and glutamine synthetase. The present study u...
Article
Electrical stimulation of vagal afferents or cardiopulmonary sympathetic afferent fibers excites C(1)--C(2) spinal neurons. The purposes of this study were to compare the responses of superficial (depth <0.35 mm) and deeper C(1)--C(2) spinal neurons to noxious chemical stimulation of cardiac afferents and determine the relative contribution of vaga...
Article
The amino acid taurine serves many functions in the nervous system serving as inhibitory neurotransmitter/neuromodulator, neurotrophin, antioxidant, and osmolyte. Taurine levels are increased following brain injury and glucocorticoid administration. Thus, the purpose of this study was to examine spinal taurine concentrations following spinal cord i...
Article
The glial enzyme glutamine synthetase (GS) is critical for central nervous system catabolism of glutamate and glutamine production. Upregulation of GS is a hallmark of reactive astrocytosis, although such induction following spinal cord injury (SCI) has not been reported. This study's purpose was to determine if GS activity is increased following S...
Article
We have shown that stimulation of cardiopulmonary sympathetic afferent fibers activates relays in upper cervical segments to suppress activity of lumbosacral spinal cells. The purpose of this study was to determine if chemical excitation (glutamate) of upper cervical cell bodies changes the spontaneous activity and evoked responses of lumbosacral s...
Article
Intraocular co-grafts of rat fetal spinal cord and dorsal root ganglia were used to examine the enhanced survival, growth, and differentiation of sensory neurons by nerve growth factor. E14 lumbar spinal segments were implanted into the anterior eye chamber of capsaicin-pretreated rats. Two weeks later, an E14 dorsal root ganglion was implanted bes...
Article
Physiological studies indicate that neurons in the upper cervical spinal cord have descending projections to the lumbosacral spinal cord and mediate inhibition of dorsal horn neurons activated from afferent input. In the present study, retrograde tracing techniques were used to examine the distribution of propriospinal neurons in C1-C2 spinal segme...
Article
Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors, including rhodopsin and beta2-adrenergic receptor. Unlike in human and cow, splice variants of this protein family in rat have not been studied extensively, and there has been no report on their existence a...
Article
The descending serotonergic system provides a powerful inhibitory input to the dorsal horn of the spinal cord. Little is known about the chemical identity of the spinal neurons that the serotonergic system innervates, although spinal enkephalinergic neurons are likely candidates. This study investigated the apposition of serotonin-immunoreactive va...
Article
Retrograde, transneuronal tracing with Bartha's strain of pseudorabies virus was used in rats to identify spinal cord, brainstem and hypothalamic loci of uterine-related neurons that could function in the regulation of uterine activity. Based on the premise that estrogen might influence such uterine-related neurons, the existence of estrogen recept...
Article
Neurogenic inflammation involves primary afferent nerve fibers that release the transmitters, substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP) and possibly nitric oxide (NO), from their peripheral terminals. These transmitters bind to receptors to (1) induce vasodilation, (2) Increase postcapillary venule permeability al...
Article
In the CNS, the amino acid glutamate serves multiple functions. It is a major excitatory neurotransmitter as well as an important carbon source for both neuronal and astrocytic metabolism. Glutamate levels are normally maintained by a biochemical pathway known as the "glutamine cycle". One neuronal enzyme, glutaminase (GT), and two glial enzymes, g...
Article
Effects of electrically stimulating the left stellate ganglion to activate cardiopulmonary sympathetic afferent (CPSA) fibers were determined on C1-C3 dorsal horn neurons in anaesthetized rats. Fifty-two of 53 dorsal horn neurons affected by CPSA stimulation were excited and one neuron was inhibited. In 6 experiments, dorsal columns and ventrolater...
Article
The presence of estrogen receptor protein and estrogen receptor messenger RNA was revealed in peripheral ganglionic neurons of the rat. The pelvic parasympathetic autonomic ganglion and lumbosacral dorsal root sensory ganglia were examined for estrogen receptor-containing neurons because they have known projections to the uterus and uterine cervix....
Article
Autonomic and sensory nerves supply the vasculature, epithelium and myometrium of the uterus. These fibers course in the pelvic and hypogastric nerves. However, recent physiological and behavioral data suggests the vagus nerves also supply the uterus and serve as additional routes for uterine information to reach the CNS. This study tested for anat...
Article
This study was directed to identify neurons in the spinal cord and brainstem that could participate in circuits for innervation of the uterus and be responsive to estrogen. Transsynaptic retrograde axonal tracing, using pseudorabies virus (PRV), in combination with estrogen receptor (ER) immunohistochemistry was used to examine the location of cell...
Article
Retrograde transport of the fluorescent tracer Fluorogold was used in combination with immunohistochemical staining for the enzyme glutaminase to identify putative glutamatergic neurons belonging to the rat spinomesencephalic tract. Glutaminase-like staining in spinal projection neurons suggests that the relay of nociceptive information from the sp...
Article
The co-localization of glutaminase and calcitonin gene-related peptide (CGRP) was examined with immunohistochemistry in the rat dorsal root ganglion (DRG). The majority of the DRG neurons were immunoreactive for glutaminase and all DRG neurons that contained CGRP also contained glutaminase. These results indicate that some DRG neurons release gluta...
Article
The spinal cord contains mu, delta and kappa opioid receptors which mediate the antinociceptive effects of opioid agonists administered onto the spinal cord. In this study, we characterized the binding sites for highly-selective mu, delta and kappa opioid radioligands and quantified the distribution of opioid binding sites in rat lumbosacral spinal...
Article
The caudal neurosecretory complex (CNc) of poecilids has previously been shown to receive serotonergic inputs. In the present study, immunohistochemical techniques were applied at the light and electron microscopic levels to characterize serotonergic terminals in the neuroendocrine nucleus. A dense plexus of varicose fibers observed in the rostral...
Article
The caudal neurosecretory complex (CNc) of poecilids has previously been shown to receive serotonergic inputs. In the present study, immunohistochemical techniques were applied at the light and electron microscopic levels to characterize serotonergic terminals in the neuroendocrine nucleus. A dense plexus of varicose fibers observed in the rostral...
Article
Full-text available
A double-peroxidase procedure was used to study the ultrastructural relationships between terminals and fibers containing three putative neurotransmitters and retrogradely identified sympathetic preganglionic neurons (SPNs) located in the intermediolateral cell column (IML) of the rat. SPNs with axons in the cervical sympathetic trunk were retrogra...
Article
The purpose of the present study was to quantify the extent to which several peptides and serotonin coexist with substance P or somatostatin in selected lumbar dorsal root ganglia of the cat. The technique for the simultaneous visualization of two antigens by immunofluorescence was used to investigate the coexistence of neuropeptides in the lumbar...
Article
This study examined the number of met-enkephalin, dynorphin A 1-8, and neurotensin immunoreactive (IR) neurons in the marginal zone (lamina I) at one thoracic (T8:cat,T9:rat), one midlumbar (L5:cat,L4:rat), and one lower lumbar or sacral (S1:cat,L6:rat) spinal cord segment in the cat and rat. Marginal zone IR neurons ranged 10-70 microns in diamete...
Article
Glutamate has been shown to be a neurotransmitter in the central nervous system of vertebrates, and it has been hypothesized that glutamate is functional as a neurotransmitter in the spinal cord dorsal horn. A monoclonal antibody to fixative-modified glutamate was used in this study to examine the light microscopic and ultrastructural profiles of g...
Article
The central gray region (lamina X) of the lumbar spinal cord in cat was examined by electron microscopy. This region consisted of three morphological zones. Medially, the first zone was comprised of ependyma which surrounded the central canal. The ependyma in the cat spinal cord was similar to most vertebrate spinal ependyma. Secondly, a subependym...
Article
This study compared the distribution of methionine enkephalin-, dynorphin A 1–8-, and neurotensin-immunoreactive (IR) perikarya in laminae I and IV–VII of selected segments of lumbar spinal cord of cat(L5) and rat(4). Immunoreactive neurons for each peptide were found throughout the dorsal horn and dorsal lamina VII but were quantified only within...
Article
Luteinizing hormone releasing hormone (LHRH)-like immunoreactivity was observed in neurosecretory neurons at mesencephalic levels of the poecilid brain. This nucleus of peptide producing neurons has been shown to project to the spinal cord neurosecretory complex in this species. LHRH-like immunoreactivity was localized in fibers and terminals surro...
Article
Brain stem projections to the neurons in the caudal neurosecretory complex (CNC) of Poecilia sphenops (molly) have been studied with HRP retrograde tracing. Using light microscopic procedures, HRP-labelled neurons were located in the reticular nucleus of the medulla (RMN) and in the vicinity of the nucleus of the medial longitudinal fascicle (NMLF)...
Article
Neurons in the dorsal tegmentum of the midbrain of the teleosts Poecilia sphenops and P. latipinna were examined by use of electron microscopy. A nucleus of neurosecretory neurons was identified in the subependymal region just dorsal to the medial longitudinal fascicle. This nucleus has been called the dorsal tegmental magnocellular nucleus (DTMN)....

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