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D L Price

Publications and source records attributed to D L Price.

At least 289 records · Page 16Linked to original sources
PubMed1985

Alzheimer's disease and related dementias: selective involvement of specific neuronal systems.

The brains of individuals with dementia due to Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS) exhibit similar neuropathological features, including neuritic plaques, neurofibrillary tangles, and the loss of specific populations of neurons. In addition, these brains show similar transmitter-specific neurochemical alterations. Recent evidence indicates that several pathological and neurochemical changes are related to diseases involving projection systems innervating the telencephalon. At least two transmitter-specific circuits, cholinergic neurons in the basal forebrain and noradrenergic neurons in the locus coeruleus, are selectively affected in many patients with these disorders. This review focuses on these systems because they provide particularly useful examples of the ways in which multidisciplinary studies can provide new clinical-pathological-chemical correlations. Strategies used in these studies are applicable to a wide variety of other neurodegenerative diseases affecting specific populations of neurons. Modern neuropathological approaches to these diseases should eventually allow investigators to directly relate pathogenic processes involving transmitter-specific neuronal populations, whose projections, physiological properties, and functions are known, with the clinical manifestations occurring in human disorders of behavior and cognition.

Aging↗
PubMed1984

Somatostatinergic neurites in senile plaques of aged non-human primates.

Using a polyclonal antibody directed against somatostatin, normal somatostatin-positive neurons and fibers were seen in the amygdala and periamygdaloid cortex of both young and aged macaques. In addition, immunoreactive structures, identical in appearance to neurites demonstrated by silver impregnation methods, were seen in the amygdala of one aged monkey that exhibited numerous senile plaques. Some of these immunoreactive neurites were associated with deposits of amyloid, as seen with thioflavin-T stains, suggesting that these were neurites of senile plaques. This study provides direct evidence for abnormalities in peptidergic neurons in brains of aged non-human primates.

Aging↗
PubMed1984

Evidence for cholinergic neurites in senile plaques.

In the neocortices and amygdalae of young and aged macaques, cholinergic axons were identified by means of a monoclonal antibody to bovine choline acetyltransferase. Many fine, linear, immunoreactive profiles were seen in these animals. In the older animals, some cholinergic axons showed multifocal enlargements along their course. In some instances, neurites with choline acetyltransferase immunoreactivity were associated with deposits of amyloid (visualized with thioflavin T fluorescence). The appearance of these amyloid-associated abnormal cholinergic processes was similar to that of neurites in senile plaques, as shown by conventional silver impregnation techniques. Cholinergic systems thus give rise to some of the neurites within senile plaques.

Aging↗
PubMed1984

Parkinson's disease: depletion of substantia nigra neurotensin receptors.

Neurotensin receptor autoradiography reveals dense binding in normal human substantia nigra. In nigra from patients with Parkinson's disease, nigral receptor binding is only about one-third of control values. 'Saturation' analysis suggests that these changes result from receptor loss. These results support a neurotensin-dopamine interaction in human nigro-striatal circuits.

Adult↗
PubMed1984

Acetylcholinesterase-immunoreactive axonal network in monkey visual cortex.

Immunocytochemistry with antibodies to human erythrocyte acetylcholinesterase (AChE) was used to demonstrate axons containing this enzyme in the visual cortex (area 17) of macaques. AChE-positive fibers were most dense in layers I, IIIB, IV, and VIB of Hassler and Wagner (I, IVA, IVC, and VIB of Brodmann) with three strata of more sparsely distributed fibers (layers II-IIIA, IIIC, and V-VIA of Hassler and Wagner [II-III, IVB, and V-VIA of Brodmann]). Layer I contained the most dense plexus of AChE-positive axons, oriented horizontally. Horizontally oriented axons were also located in layers IIIB, IIIC, IV, and V of Hassler and Wagner (IVA, IVB, IVC, and V of Brodmann). Layer VIB contained axons of variable orientation, apparently afferent to cortex. Moderately stained neuronal perikarya were occasionally encountered in layer VIB and superficial white matter, but no intensely stained neurons were seen.

Acetylcholine↗
PubMed1984

Autosomal dominant inheritance of hereditary canine spinal muscular atrophy.

Hereditary canine spinal muscular atrophy ( HCSMA ) is a motor neuron disease in Brittany spaniels. Three phenotypes are recognized (accelerated, intermediate, and chronic) and are distinguished on the basis of rate of progression and age at onset. Breeding studies within a kindred of more than 125 dogs (Brittany spaniel and beagle-Brittany outcrosses ) have established an autosomal dominant inheritance for HCSMA . Pups homozygous for the trait have accelerated disease whereas heterozygous dogs have intermediate or chronic disease. The reason for the two phenotypes in heterozygotes is under study. HCSMA provides a unique opportunity to study the genetic and pathophysiological mechanisms of a motor neuron disease, and findings may have broad relevance to investigations of autosomal dominant degenerative disorders of the central nervous system.

Animals↗
PubMed1984

Acetylcholinesterase activity in senile plaques of aged macaques.

A modified acetylcholinesterase (AChE)-histochemical technique, which demonstrates axonal morphology to a high degree, was used to examine the neocortices of aged monkeys. This approach disclosed slender linear axonal profiles in young animals. In older monkeys, there was a variety of abnormalities of AChE-containing fibers, including multifocal distensions of individual fibers and aggregations of neurite-sized, AChE-rich swellings. Combined with thioflavin-T staining to visualize amyloid, this histochemical technique showed that some of these AChE-containing fibers were present in proximity to deposits of amyloid. This association suggests that abnormal AChE-rich axons participate in the formation of some senile plaques in the neocortices of aged nonhuman primates. While it is probable that many of these AChE-rich fibers are axons of cholinergic neurons residing in the basal forebrain, it is also likely that some of these fibers are derived from noncholinergic neuronal populations known to synthesize AChE. Immunocytochemical strategies can be used to assess the involvement of other systems, including cholinergic, noradrenergic, dopaminergic, somatostatinergic, and serotonergic neurons in the formation of senile plaques in the brains of aged nonhuman primates.

Acetylcholinesterase↗
PubMed1984

Control of axonal caliber by neurofilament transport.

The role of neurofilaments, the intermediate filaments of nerve cells, has been conjectural. Previous morphological studies have suggested a close relationship between neurofilament content and axonal caliber. In this study, the regenerating neuron was used as a model system for testing the hypotheses that neurofilaments are intrinsic determinants of axonal caliber, and that neurofilament content is controlled by the axonal transport of neurofilaments. This system was chosen because previous studies had shown that, after axotomy, axonal caliber was reduced within the proximal stump of the regenerating nerve and, because the relative amount of neurofilament protein undergoing axonal transport in regenerating axons was selectively reduced. The relationship between axonal caliber and neurofilament number was examined in a systematic fashion in both regenerating and control motor axons in rat L5 ventral root. Reconstruction of the spatial and temporal sequences of axonal atrophy in the proximal stump after axotomy showed that reductions in axonal caliber were first detected in the most proximal region of the root and subsequently progressed in a proximal-to-distal direction at a rate of 1.7 mm/day, which is identical to the rate of neurofilament transport in these neurons. Quantitative ultrastructural studies showed that these reductions in caliber correlated with a proportional decrease in the number of axonal neurofilaments but not microtubules. These results support the hypotheses that neurofilament content is a major intrinsic determinant of axonal caliber and that neurofilament content is controlled by the axonal transport of neurofilaments. On this basis, we suggest a role for neurofilaments in the control of axonal volume.

Animals↗
PubMed1984

Topography of the magnocellular basal forebrain system in human brain.

In primates, the large neurons in the nucleus basalis of Meynert (nbM), nucleus of the diagonal band of Broca (dbB), and medial septum are part of a cholinergic system with direct projections to amygdala, hippocampus, and cortex. Recent evidence indicates that neurons of this system selectively degenerate in individuals with Alzheimer's disease (AD) and suggests that degeneration of these cells contributes to the loss of presynaptic cortical cholinergic markers which occurs in these patients. The present report describes the topographical distribution of these large intensely basophilic, basal forebrain neurons in human brain. Rostrally, neurons of this magnocellular system are present in the medial septum and the dorsal and ventral parts of the nucleus of the dbB. The largest number occur in the nbM, which is situated in the substantia innominata below the globus pallidus. Caudally, large nbM-type neurons are found along the ventral and lateral edges of the globus pallidus. Neurons of this type are also encountered in the white matter below the putamen and nucleus accumbens, at the edges of the anterio commissure, in the white matter laminae of the globus pallidus and within and at the medial edge of the genu of the interal capsule. Directions for dissection of this system in human brain are given in an Appendix.

Acetylcholinesterase↗
PubMed1984

Neurofilamentous axonal swellings as a normal finding in the spinal anterior horn of man and other primates.

To define the nature and extent of axonal swellings in the normal spinal anterior horn, we studied the spinal cords of patients five days to 83 years of age from a general autopsy population. Axonal swellings were routinely found in the anterior horn of the cervical and lumbosacral spinal cord. The swellings measure 5-50 micron in diameter and are most numerous at the anterior edge of the anterior horn. They first appear about five months of age and appear to increase in number until about 20 years of age, with no increment thereafter. Ultrastructurally, they are filled with neurofilaments and surrounded by a thin myelin sheath. Most are probably aberrant components of motor axons. Identical axonal swellings, in the same anatomical site, were found in the spinal cords of cynomolgus and rhesus monkeys. On the basis of their natural history and morphologic features, they should be distinguished from the neuroaxonal dystrophy of aging. The largest of them resemble the neurofilamentous axonal swellings of early onset motor neuron disease but occur in much smaller numbers. Moreover, location on the proximal axon could not be demonstrated for any of these swellings. An awareness of this normal phenonemon is essential for the interpretation of axonal swellings in the spinal cord.

Adolescent↗
PubMed1984

Synaptic neurochemical alterations associated with neuronal degeneration in an inherited cerebellar ataxia of Gordon Setters.

Canine Inherited Ataxia (CIA) is an autosomal recessive cerebellar disease of Gordon Setters associated with degeneration of Purkinje and granule cells. To define specific biochemical correlates of neuronal loss, synaptic neurochemical parameters were measured in three cerebellar regions (vermis, "pars intermedia," and hemisphere) at early and late stages of this disease. At one and a half years of age, affected dogs showed the most severe lesions in the "pars intermedia," with a 39% decrease in the number of Purkinje cells and a 29% decrease in granule cells. Neurochemical measurements demonstrated decreased [3H]muscimol binding and elevations in norepinephrine concentration (248% above control) and [3H]glutamate receptor binding (118% above control). At five years of age, reduction of Purkinje cells in the three cerebellar regions ranged from 65 to 91% while loss of granule cells was between 13 and 53%. [3H]Muscimol binding remained low throughout the cerebellum (38 to 59% of control) and norepinephrine concentration and [3H]glutamate binding were markedly reduced from the levels observed at one and a half years. Glutamate decarboxylase activity, [3H]QNB binding and GABA concentration were relatively unaffected. Our results indicate that neurochemical parameters associated with cerebellar neuronal systems demonstrate specific alterations in a chronic degenerative disorder. This study also indicates the importance of evaluating neurochemical measurements with regard to both spared and degenerating neuronal systems and emphasizes the role of compensatory neurochemical alterations in cerebellar degenerative disorders.

Animals↗
PubMed1983

Immunocytochemical identification of cholinergic neurons in the monkey central nervous system using monoclonal antibodies against choline acetyltransferase.

A monoclonal antibody directed against rat brain choline acetyltransferase (ChAT) was used to stain cholinergic nerve cells within the brain and spinal cord of macaques. ChAT immunoreactivity was seen in motor neurons of the brainstem and spinal cord, in large neurons of the striatum, and in large neurons in the basal forebrain (medial septum--diagonal band--nucleus basalis complex); each of these groups of neurons is believed to be cholinergic. The ability to visualize cholinergic neurons in the nervous system of primates provides a new approach to the study of cholinergic systems in health and disease.

Animals↗
PubMed1983

Alzheimer's disease: a disorder of cortical cholinergic innervation.

Great emphasis is being placed on identification of neurotransmitter systems involved in the symptomatic manifestations of neurological and psychiatric disorders. In the case of Alzheimer's disease, which now seems to be one of the most common causes of mental deterioration in the elderly, compelling evidence has been developed that acetylcholine-releasing neurons, whose cell bodies lie in the basal forebrain, selectively degenerate. These cholinergic neurons provide widespread innervation of the cerebral cortex and related structures and appear to play an important role in cognitive functions, especially memory. These advances reflect a close interaction between experimental and clinical neuroscientists in which information derived from basic neurobiology is rapidly utilized to analyze disorders of the human brain.

Alzheimer Disease↗
PubMed1983

Basal forebrain neurons in the dementia of Parkinson disease.

Demented patients with Parkinson disease share certain neuropathological and neurochemical features with patients suffering from Alzheimer disease. Recently, loss of cholinergic neurons in the basal forebrain, particularly the nucleus basalis of Meynert, has been implicated in the pathophysiology of Alzheimer disease. The present investigations of 12 patients with Parkinson disease demonstrates that the demented patients with this disease also show a selective loss of cells in the nucleus basalis of Meynert, thus providing an important link between the dementias of Alzheimer disease and Parkinson disease.

Adult↗
PubMed1983

Amyotrophic lateral sclerosis: alterations in neurotransmitter receptors.

Loss of motor neurons is the primary pathological hallmark of amyotrophic lateral sclerosis. Drug and neurotransmitter receptors are neuronal markers and can be indicators of neuronal connectivity. Knowledge of alterations in receptors in amyotrophic lateral sclerosis should contribute to our understanding of normal spinal cord neurotransmitter systems as well as of the pathophysiology of amyotrophic lateral sclerosis. We therefore used a sensitive, light microscopic in vitro labeling receptor autoradiographic technique to map and quantitate muscarinic cholinergic, glycinergic, and benzodiazepine receptors in three levels of spinal cord from six patients with amyotrophic lateral sclerosis and six age- and sex-matched control patients. In control tissues, the receptor distributions were similar in the three levels of spinal cord and also similar to those found in previous studies with animals. In amyotrophic lateral sclerosis, major reductions in receptor densities were noted in Rexed layer IX, the region containing motor neurons. Reductions were noted in other laminae as well, particularly for muscarinic receptors. The changes in muscarinic receptors were caused solely by changes in high-affinity agonist sites. Reductions in glycine and muscarinic receptors were highly correlated with the degree of motor neuron loss found in the amyotrophic lateral sclerosis patients. The findings in this study point out the usefulness of this receptor mapping technique in understanding the changes in neuronal populations that occur in the degenerative neurological diseases.

Adult↗
PubMed1983

Cytoskeletal disorganization induced by local application of beta, beta'-iminodipropionitrile and 2,5-hexanedione.

Beta, beta'-Iminodipropionitrile and 2,5-hexanedione are neurotoxins that produce neurofilamentous axonal swellings. The swellings produced experimentally with these agents are similar in structure but different in distribution. Neither the relationships between these agents nor the mechanisms of action are known. In this study local effects on nerve fibers were compared following injection of beta, beta'-iminodipropionitrile and 2,5-hexanedione beneath the perineurium of rat sciatic nerves. Soon after injection, 2,5-hexanedione reproduced the distinctive cytoskeletal disorganization previously described with beta, beta'-iminodipropionitrile: microtubules collected into a central channel, with neurofilaments segregated in a surrounding subaxolemmal ring. Later, the beta, beta'-iminodipropionitrile-injected nerves developed local neurofilaments accumulations, reproducing the neurofilamentous axonal swellings characteristic of systemic intoxication with these agents. The results indicate that both these agents have direct local effects on the axonal cytoskeleton and probably are similar in mechanism of action. Both these agents appear to segregate neurofilaments from the rest of the axonal cytoskeleton. This segregation may prevent the normal proximal-to-distal transport of neurofilaments, resulting in the formation of neurofilamentous axonal swellings.

Animals↗
PubMed1983

Canine neuroaxonal dystrophy.

Canine neuroaxonal dystrophy, a newly recognized familial disorder in Rottweiler dogs, is characterized by progressive sensory ataxia. Two of four dogs studied clinically were autopsied and the cerebellum was mildly atrophic. Massive numbers of axonal spheroids were present in many regions of the neuraxis but were most prominent in the dorsal horn of the spinal cord and the nuclei gracilis and cuneatus. Ultrastructurally, spheroids appeared to be swellings of distal axons which were filled with accumulations of smooth membrane-bound vesicles, membranous lamellae, dense bodies, and other organelles. Neuropathological changes were similar to those identified in human neuroaxonal dystrophy.

Animals↗