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Biomedical subjects

J C Hedreen

Publications and source records attributed to J C Hedreen.

At least 55 records · Page 3Linked to original sources
PubMed1988

Pathology in brainstem regions of individuals with primary dystonia.

Examination of brains from four individuals with the clinical diagnosis of primary dystonia revealed histopathologic abnormalities in two cases. A 29-year-old man with a 15-year history of dystonia musculorum deformans (DMD) had numerous neurofibrillary tangles (NFT) and mild neuronal loss within the locus ceruleus; occasional NFT were also recognized in the substantia nigra pars compacta, pedunculopontine nucleus, and dorsal raphe nucleus. A 68-year-old man with a 35-year history of Meige syndrome had moderate-to-severe neuronal loss in several brainstem nuclei, including the substantia nigra pars compacta, locus ceruleus, raphe nuclei, and pedunculopontine nucleus. Infrequent NFT were also noted in substantia nigra. An examination of these and other brain regions in a 10-year-old boy with a 6-year history of DMD and a 50-year-old woman with a 3-year history of spasmodic torticollis did not disclose similar abnormalities.

Adult↗
PubMed1988

Sigma receptors in post-mortem human brains.

The pharmacological profile and regional distribution of sigma receptors in human autopsy brains were determined using [3H]-haloperidol as the ligand, in the presence of 50 nM spiperone to block binding to D2 dopamine sites. Specific binding in the cerebellum was to a single and saturable class of receptors with Kd = 0.95 +/- 0.12 nM and maximum binding = 358 +/- 13 fmol/mg of protein. Inhibition studies of the nondopamine [3H]haloperidol binding site in human cerebellar membranes revealed stereospecific binding and a pharmacological profile similar to that of specific sigma binding sites characterized in rodent brains using [3H]haloperidol, N-[3H]allylnormetazocine and di-o-[3H]-tolylguanidine as radioligands. The densities of sigma sites in the brain were highest in the cerebellum, nucleus accumbens and cerebral cortex. A post-mortem simulation study was performed with guinea pig brains due to the concern that sigma receptors might deteriorate in the human brain before assay. The results showed that this site was remarkably stable and insensitive to long periods of cooling or freezing.

Adult↗
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

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

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

Morphologic and neurochemical studies of embryonic brain development in murine trisomy 16.

Telencephalic and diencephalic/brainstem regions from embryonic trisomy-16 mice (Ts16) between gestational days 15-18 were analyzed for alterations of morphologic and neurochemical parameters and compared to phenotypically normal littermates. Mean trisomic wet weights from both regions were significantly diminished (greater than 20%) and total protein content was reduced. Ratios of the thickness of the ventricular (germinal) zone to the thickness of the whole cortex were increased, suggesting a delay in neuronal differentiation. Pre- and postsynaptic markers for GABAergic, cholinergic, catecholaminergic and serotonergic transmitter systems were compared. A significant impairment of the trisomic brain catecholaminergic and serotonergic system development was observed, based upon regional reductions in norepinephrine, dopamine and serotonin content. Choline acetyltransferase activity in the diencephalon/brainstem was reduced by 21-26% in contrast to normal levels within the cerebral hemispheres. Presynaptic GABAergic markers were not affected in the Ts16 embryos. It is concluded that although a genetic imbalance involving chromosome 16 in the mouse embryo produces a delay in neurogenesis, it has a more selective effect on the catecholaminergic, serotonergic and cholinergic systems than on GABAergic neurons.

Amino Acids↗
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

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↗
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

Topographic analysis of the innervation of the rat neocortex and hippocampus by the basal forebrain cholinergic system.

The basal forebrain-cortex connections of the rat were topographically mapped by retrograde tracer methods; and their contribution to the cholinergic innervation of the cortex was assessed by excitotoxin lesions placed in the rostral and caudal aspects of the complex. Discrete injections of tracer into frontal cortex labeled the prominent multipolar acetylcholinesterase (AchE)-positive cells of the ventromedial globus pallidus. Injections of tracer into the parietal cortex labelled cells in the ventral globus pallidus, the underlying substantia innominata, and the lateral hypothalamus. Separate injections of Fast Blue and Nuclear Yellow in the frontal and in the parietal cortex resulted in double-labeled cells in the ventral globus pallidus, which indicates that at least some of these cells may possess collateralizing axons. The cingulate cortex is innervated predominantly by neurons in the nucleus of the horizontal limb of the diagonal band. The occipital cortex was also shown to receive a projection primarily from the nucleus of the horizontal limb of the diagonal band. The hippocampal formation is innervated primarily by cells located in the vertical limb of the diagonal band and in the medial septum. Consistent with the results of the retrograde tracing studies, excitotoxin lesions affecting the diagonal band and medial septum decreased choline acetyltransferase (CAT) activity up to 40% on the occipital cortex and by 64% in the hippocampus, but did not affect CAT activity in the rostral neocortex. In contrast, ibotenate lesions of the caudal ventral globus pallidus and substantia innominata caused decreases in CAT activity in the frontal cortex of up to 65% without affecting enzyme activity in the hippocampal formation. The results of the present study provide details on the topographic organization of the cortical projections originating in the basal forebrain complex and indicate that these neurons are the predominant source of cortical cholinergic innervation.

Acetylcholine↗
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

The nucleus basalis in Huntington's disease.

The nucleus basalis of Meynert (nbM) provides most of the cholinergic input to the cerebral cortex. The loss of cortical choline acetyltransferase (CAT) activity in Alzheimer's disease (AD) and senile dementia of the Alzheimer's type (SDAT) appears to be related to a severe depopulation of the nbM in this dementia. In Huntington's disease (HD), by contrast, there is no loss of cortical CAT activity. The present quantitative study indicates that (1) there is no significant loss of neurons from the nbM in HD, and (2) that the previously described cytologic changes in the neurons of this nucleus in HD patients do not differ significantly from controls. These findings are consistent with the working hypothesis that the types of dementia associated with reductions of neocortical CAT activity are characterized by dysfunction or death of neurons in the nbM, but dementing disorders with normal neocortical CAT activity manifest no major abnormalities in this cholinergic nucleus of the basal forebrain.

Aged↗
PubMed1983

Pick's disease (lobar sclerosis): depletion of neurons in the nucleus basalis of Meynert.

The nucleus basalis of Meynert (nbM) has been implicated in the pathogenesis of the presynaptic cholinergic deficiency in the cerebrum of patients with Alzheimer's disease. To further define the role of this cholinergic basal forebrain nucleus in dementia, we examined the nbM in two patients with lobar sclerosis, or Pick's disease (PD). The brains of both of these patients showed substantial reductions in the number of nerve cells in many neuronal populations, including the nbM. Our observations of the changes in the nbM are correlated with previous investigations of cholinergic markers in PD.

Basal Ganglia↗