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D L Price

Publications and source records attributed to D L Price.

At least 271 records · Page 15Linked to original sources
PubMed1985

Aluminum intoxication: a disorder of neurofilament transport in motor neurons.

In the rabbit, intrathecal administration of aluminum salts (AlCl3) induces accumulation of neurofilaments in nerve cells of the central nervous system. In motor neurons, the spatial pattern of neurofilamentous accumulation following aluminum intoxication suggests a defect in the axonal transport of neurofilament proteins. To test this hypothesis, we examined the distribution of radioactive cytoskeletal proteins in sciatic nerves of intoxicated and control animals. In the nerves of aluminum-injected animals, there was a 40% reduction in the relative amount of radioactive neurofilament proteins compared to tubulin. These results suggest that an abnormality in neurofilament transport may be important in the pathogenesis of the neurofibrillary pathology induced by aluminum intoxication.

Aluminum↗
PubMed1985

Glutamic acid decarboxylase-like immunoreactive neurites in senile plaques.

In the neocortex of an aged (26-year-old) rhesus monkey, a small percentage of abnormal neurites within some senile plaques (defined by the presence of amyloid) were immunoreactive for glutamic acid decarboxylase. This suggests that gamma-aminobutyric acid-synthesizing neurons may contribute to plaque formation in the aged brain.

Aging↗
PubMed1985

Cholinergic neurons in the telencephalon of the reptile Caiman crocodilus.

Choline acetyltransferase (ChAT) immunohistochemistry was used to characterize the distribution of cholinergic neurons in the telencephalon of the reptile, Caiman crocodilus. ChAT-positive cell bodies were observed within the small-celled portion of the ventrolateral area of the telencephalon (VLA s.c.), a region previously considered comparable to the mammalian caudate nucleus and putamen. A large field of cholinergic neurons was observed within the ventral paleostriatum (VP), a region comparable to the substantia innominata and ventral pallidum of mammals. Cholinergic neurons were also observed within cranial motor nuclei of the brainstem, within the isthmic nucleus and within portions of the lateral reticular formation of the pons and medulla. A rich plexus of cholinergic fibers was observed within the intermediate and deep layers of the optic tectum. The results of this study indicate that many aspects of cholinergic system organization are similar in caiman and mammals, and suggest a common derivation of these systems from ancestral forms.

Acetylcholinesterase↗
PubMed1985

Neurotransmitter receptor alterations in Huntington's disease: autoradiographic and homogenate studies with special reference to benzodiazepine receptor complexes.

In vitro receptor autoradiography was used to construct semiquantitative maps of subtypes of muscarinic cholinergic (labeled with [3H]N-methylscopolamine), benzodiazepine ([3H]flunitrazepam), gamma-aminobutyric acid ([3H]muscimol), dopamine, and serotonin ([3H]spiperone) receptors in frontal cortex, parietal cortex, caudate, putamen, and globus pallidus in tissue sections from 5 patients with clinically well-evaluated Huntington's disease and 5 controls matched with respect to age, sex, and postmortem delay. Homogenates were prepared from the remaining cortical and striatal tissue and used to characterize pharmacologically these same receptors, as well as histamine, adenosine, and nitrendipine receptors. Neuronal loss and gliosis were assessed in the contralateral formalin-fixed caudate and putamen. All binding sites measured (except serotonin) were reduced relative to control values in striatum primarily because of changes in the number of receptors rather than in affinity. Autoradiographic studies generally revealed that these changes were greater in the caudate than the putamen, paralleling the more severe neuropathological changes present in the caudate. In addition, autoradiographic studies demonstrated an increase in gamma-aminobutyric acid-related receptors in the globus pallidus. In the cortex, receptor alterations were limited to an increase in the number of benzodiazepine receptors in the frontal cortex which was most prominent in superficial cortical layers.

Autoradiography↗
PubMed1985

Abnormalities of the nucleus basalis in Down's syndrome.

One of the most striking manifestations of Down's syndrome is profound mental retardation. Furthermore, after 35 years of age, many patients with Down's syndrome develop clinical and pathological features of Alzheimer's disease. Since brains of patients with Alzheimer's disease show significant loss of neurons in the nucleus basalis of Meynert (nbM), we sought to establish normal standards of nbM neurons in persons with Down's syndrome and to determine whether reductions in the number of neurons occur with increasing age. The number and size of neurons in the nbM were measured in selected sagittal sections from 5 patients with Down's syndrome and 5 age-matched controls. The patients (age range, 16 to 56 years) had 29% fewer nbM neurons than controls, and the oldest patient had the lowest cell count of all subjects. The size of nbM neurons did not differ significantly between the two groups. Our results show that the nbM contains fewer neurons in young persons with Down's syndrome than in normal controls and suggest that the number of these nerve cells may be further reduced in older persons with Down's syndrome.

Adolescent↗
PubMed1985

Catecholaminergic neurites in senile plaques in prefrontal cortex of aged nonhuman primates.

Immunocytochemical studies, using a polyclonal antibody directed against tyrosine hydroxylase, identified catecholaminergic axons in prefrontal cortex of young and aged nonhuman primates. Aged monkeys, who showed cortical senile plaques in silver stains, had swollen tyrosine hydroxylase-immunoreactive axons in neocortex. Some of these abnormal processes were associated with deposits of amyloid (visualized by thioflavin-T fluorescence) and were similar in appearance to neurites demonstrated by silver impregnation methods. This study provides evidence for structural abnormalities in catecholaminergic axons/nerve terminals in the neocortices of aged primates.

Adrenergic Fibers↗
PubMed1985

Noncollateral projections of basal forebrain neurons to frontal and parietal neocortex in primates.

To test the hypothesis that axons of the basal forebrain cholinergic system collateralize to innervate widely separated areas of cortex, two distinct, retrogradely transported fluorescent dyes were injected into discrete neocortical regions of three macaques. In two monkeys, True Blue was injected into parietal cortex and Nuclear Yellow into frontal cortex; in a third monkey, placement of the dyes was reversed. Following these large (3-10 microliters total) injections, neurons single labeled with either Nuclear Yellow or True Blue were seen throughout most of the ipsilateral nucleus basalis of Meynert and nucleus of the diagonal band of Broca. Neurons projecting to either frontal or parietal cortex were most heavily concentrated in the anteromedial aspect of the basal forebrain. A small number of labeled neurons was also seen in the contralateral basal forebrain. Cells single labeled with either True Blue or Nuclear Yellow were frequently adjacent to one another, but in no case was a neuron labeled with both dyes. Thus, individual neurons of the basal forebrain complex do not appear to innervate both frontal and parietal lobes of monkeys. This finding is consistent with recent studies in rodents which suggest that basal forebrain neurons innervate relatively small, restricted cortical fields.

Animals↗
PubMed1985

Changes in neurofilament transport coincide temporally with alterations in the caliber of axons in regenerating motor fibers.

The delivery of neurofilaments via axonal transport has been proposed as an important mechanism for regulating axonal caliber. If this hypothesis is correct, alterations in axonal caliber should appear coincident with changes in the delivery of neurofilaments to the axon. The purpose of this study was to determine whether alterations in the caliber of axons in the proximal stumps of transected motor fibers precede, coincide with, or occur substantially later than changes in the delivery of neurofilaments via axonal transport. Between 3 d and 12 wk after crushing the sciatic nerves of 7-wk-old rats, lumbar motor neurons were labeled by the intraspinal injection of [35S]methionine. In neurons labeled between 3 d and 6 wk after axotomy, the relative amount of neurofilament protein in the slow component, as reflected by the ratio of the radioactivities of the 145-kD neurofilament protein to tubulin, was reduced to 30-40% of the control value. Moreover, as determined by immunoreactivity on blots, the amounts of neurofilament protein and tubulin in these nerve fibers were reduced fourfold and twofold, respectively. Thus, changes in the ratio of labeled neurofilament protein to tubulin correlated with comparable changes in the quantities of these proteins in nerve fibers. This decrease in the quantity of neurofilament proteins delivered to axons coincided temporally with reductions in axonal caliber. After regeneration occurred, the delivery of neurofilament proteins returned to pre-axotomy levels (i.e., 8 wk after axotomy), and caliber was restored with resumption of normal age-related radial growth of these axons. Thus, changes in axonal caliber coincided temporally with alterations in the delivery of neurofilament proteins. These results suggest that the majority of neurofilaments in these motor fibers continuously move in the anterograde direction as part of the slow component of axonal transport and that the transport of neurofilaments plays an important role in regulating the caliber of these axons.

Animals↗
PubMed1985

Canine inherited ataxia: ultrastructural observations.

Canine Inherited Ataxia is inherited as an autosomal recessive trait in Gordon Setters. This animal model shares features with certain human cerebellar degenerations and offers the opportunity to examine brain tissue at various stages during the evolution of disease. The present investigation focuses on the morphometric and ultrastructural changes of cerebellar neurons. Purkinje and granule cells are the principal intrinsic neurons at risk. The size of Purkinje cells decreases, axonal degeneration is an important feature of the pathology, and synaptic abnormalities occur in the cerebellar glomeruli and deep nuclei of the cerebellum. The sequence and nature of synaptic changes in the molecular layer suggest that the degenerative process begins in Purkinje cells and that granule cells may be secondarily affected.

Afferent Pathways↗
PubMed1985

Neurobiological studies of transmitter systems in aging and in Alzheimer-type dementia.

Dysfunction and death of specific neuronal systems are important processes occurring in aging and in Alzheimer's and in Parkinson's disease. The neuropathology and neurochemistry of some of the neuronal systems at risk in these settings are subjects of active research; the nature and consequences of these cellular pathologies have begun to be clarified. The availability of animal models (including aged monkeys, macaques with cholinergic deficiencies, and monkeys with MPTP-induced nigrostriatal pathology, all of which recapitulate certain features of human aging or disease) allow the opportunity to assess the efficacies of new pharmacotherapies, neural grafts, and trophic factors. These approaches can be monitored by behavioral testing and, in some instances, by in vivo imaging methods, which can in turn be correlated with morphologic and chemical analyses of brain. Demonstration of the efficacy of these procedures in nonhuman primates would have profound implications on the development of new therapies designed to alleviate the effects of aging and disease on the human brain.

Acetylcholinesterase↗
PubMed1985

Alzheimer's disease.

Significant progress has been made in identifying changes in cholinergic, monoaminergic, and peptidergic neurotransmitter systems in the brains of individuals with Alzheimer's disease. Moreover, neurobiological approaches are beginning to reveal the relationships between these neurotransmitter abnormalities and histological hallmarks of the disease, i.e. neurofibrillary tangles, senile plaques, and loss of specific populations of nerve cells. However, to date, the clinical consequences of these specific neurotransmitter changes remain to be elucidated, the cause of this disorder has not been identified, and no effective therapy is yet available.

Alzheimer Disease↗
PubMed1985

A modified histochemical technique to visualize acetylcholinesterase-containing axons.

An improved histochemical method for light microscopic demonstration of acetylcholinesterase (AChE) has been developed. Axonal, dendritic, and perikaryal staining are well delineated, both in areas of low AChE content, such as cerebral cortex, and in areas of high AChE content, such as neostriatum. Axonal staining, including arborizations, stands out against a clear background devoid of diffuse reaction product.

Acetylcholinesterase↗
PubMed1985

Parkinson's disease: loss of neurons from the ventral tegmental area contralateral to therapeutic surgical lesions.

Decreased numbers of pigmented neurons of the dopaminergic nigrostriatal system are the most striking pathology in the brains of individuals with Parkinson's disease (PD), but it is clear that neurons in the locus ceruleus, vagal nuclei, and nucleus basalis of Meynert are also affected in this disease. Because neurochemical evidence suggested that the mesolimbic dopaminergic system originating in the ventral tegmental area (VTA) may also be involved, the present study was designed to evaluate the mesolimbic dopamine system in PD by counting pigmented neurons in the VTA contralateral to therapeutic lesions placed in the basal ganglia or thalamus. In PD, VTA neurons were depleted to 36 to 55% of control values. Moreover, the VTA showed excessive free pigment, a marker for death of pigmented neurons. These changes may be important in disorders of movement or mentation occurring in PD.

Adult↗
PubMed1985

Slow axonal transport in acrylamide neuropathy: different abnormalities produced by single-dose and continuous administration.

Alterations in axonal caliber and neurofilament content have been associated with altered neurofilament transport in several models of neurofibrillary degeneration. Acrylamide intoxication provides a prototype of distal axonal degeneration, the most frequent pattern of axonal pathology in human and experimental neurotoxic injury. Neurofibrillary changes are a variable and often minor aspect of the early pathological changes observed in acrylamide intoxication, and previous studies of slow axonal transport have produced conflicting results. In this study, we have correlated slow axonal transport, specifically neurofilament transport, with structural changes in the sciatic nerve complex of rats exposed to acrylamide. To study direct toxic effects of acrylamide, young rats were given a single dose of acrylamide (75 mg/kg, i.p.). A second group received daily injections of acrylamide at a lower dose (30 mg/kg, i.p.) in order to study animals with established acrylamide neuropathy. The slow component of axonal transport was labeled by intraspinal injections of [35S] methionine. Transport of individual slow component polypeptides was compared to profiles obtained from age-matched controls. Similarly intoxicated rats were perfused for morphometric and morphological studies. Results demonstrate that two different abnormalities of the slow component of axonal transport arise at different stages during the development of experimental acrylamide neuropathy. Both patterns of altered transport have structural correlates which reflect the changes in neurofilament transport. Following a single high dose, there was a modest retardation of the leading edge of the slow component. At this time, neurofilaments accumulated in proximal axons with formation of axonal swellings. During chronic administration, when distal axonal degeneration was present, the proportion of neurofilaments in the slow component was markedly reduced, and there was prominent loss of caliber in proximal axons. We suggest that these early changes represent a direct toxic effect of acrylamide on slow transport, whereas the later changes reflect reordering of slow transport as a neuronal response to toxin-induced axonal injury. This latter effect is of sufficient magnitude to obscure the acrylamide-induced retardation of slow transport.

Acrylamide↗
PubMed1985

Slowing of neurofilament transport and the radial growth of developing nerve fibers.

Several lines of evidence indicate that neurofilaments are major intrinsic determinants of axonal caliber in myelinated nerve fibers, and that the delivery of neurofilaments by slow axonal transport is an important mechanism by which neurons regulate axonal caliber. To further clarify the relationship between neurofilament transport and axonal caliber, we examined transport in developing motor fibers of rat sciatic nerve. In 3-, 10-, 12-, and 20-week-old rats, lumbar motor neurons were labeled by the intraspinal injection of radioactive amino acids, and the distributions of labeled cytoskeletal proteins within the sciatic nerve were analyzed at various times afterwards using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gel fluorography, and liquid scintillation spectroscopy. There was a progressive decline in the velocity of neurofilament transport with increasing distance along axons undergoing radial growth. By examining transport in different regions of the nerve in animals of the same age, we separated age-dependent reductions in velocity from those related to position along the nerve. The cross-sectional areas of these motor axons (in the L5 ventral root) increased linearly between 3 and 18 weeks of age. Quantitative electron microscopic analysis at 3 and 10 weeks of age revealed that neurofilament density was comparable in fibers of all calibers, indicating that the radial growth of these myelinated nerve fibers correlates with a proportional increase in neurofilament content. We propose that progressive reduction in the velocity of neurofilament transport along the nerve provides for radial growth during development.

Amino Acids↗
PubMed1985

Axonal transport of neurofilament proteins in IDPN neurotoxicity.

The neurofibrillary changes produced by IDPN are the consequence of the ability of the agent to impair the slow axonal transport of neurofilaments. The susceptibility of various neurons to this effect depends upon their neurofilament content; neurofilament-rich large caliber axons are severely affected. In motor neurons the half-velocities of neurofilament proteins are reduced 2-10 fold, while tubulin and other slow component constituents are only mildly altered. Optic nerve fibers are intermediate in vulnerability, and small neurofilament-poor fibers have little change in slow transport. The agent acts directly on the axon, and the transport defect is expressed all along the course of susceptible axons. Similar alterations in neurofilament transport have recently been found with 3,4-dimethyl-2,5-hexanedione, indicating that similar pathogenetic mechanisms can occur with toxic agents other than IDPN.

Animals↗