Biomedical subjects

M F Mazurek

Publications and source records attributed to M F Mazurek.

At least 55 records · Page 3Linked to original sources

PubMed1988

Somatostatin and neuropeptide Y concentrations in pathologically graded cases of Huntington's disease.

Somatostatin and neuropeptide Y concentrations have previously been reported to be increased in the basal ganglia in Huntington's disease (HD). In the present study we have extended these findings by examining both somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) in cases of HD, which were graded according to the severity of pathological degeneration in the striatum. In addition, we surveyed a large number of subcortical nuclei and cortical regions for alterations. Both SLI and NPYLI were significantly increased about threefold in the caudate, putamen, and the nucleus accumbens. Increases in mild and severe grades were similar, which is consistent with a relative but not absolute sparing of striatal aspiny neurons in which somatostatin and neuropeptide Y are colocalized. Significant increases of NPYLI were also found in the external pallidum, subthalamic nucleus, substantia nigra compacta, claustrum, anterior and dorsomedial thalamus, bed nucleus of the stria terminalis, and locus ceruleus. SLI was significantly increased in the external pallidum, red nucleus, and locus ceruleus. Measurements of both neuropeptides were made in 24 regions of the cerebral cortex. Significant increases in both NPYLI and SLI were found in the frontal cortex (Brodmann areas 6, 8, 9, 10, 11, and 45) and temporal cortex (Brodmann area 21), whereas NPYLI was also increased in Brodmann areas 12, 20-22, 25, and 42. Alterations in the cerebral cortex were as pronounced in cases with mild striatal pathological changes as in those with severe striatal pathological changes. These alterations may occur early in HD and could reflect a selective sparing of somatostatin-neuropeptide Y cortical neurons combined with cortical atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1988

Somatostatin and neuropeptide Y immunoreactivity in Parkinson's disease dementia with Alzheimer's changes.

Somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were measured in postmortem brain tissue from 12 control patients and 13 demented Parkinsonian patients who had Alzheimer-type cortical pathology. Twenty-two cortical regions were examined. Significant reductions in cortical SLI were found in 17 regions, while significant reductions in cortical NPYLI were found in nine regions. The reductions in SLI were typically 50-60%, while NPYLI reductions were 20-30%. These findings are similar to those in Alzheimer's disease (AD) and are consistent with a previous report of a dissociation between reductions in SLI and NPYLI in Parkinson's disease (PD) with dementia.

Aged↗

PubMed1988

A detailed examination of substance P in pathologically graded cases of Huntington's disease.

Substance P concentrations have been found to be reduced in the basal ganglia in Huntington's disease (HD). In order to further examine this finding in the present study we measured substance P-like immunoreactivity (SPLI) in cases of HD which had been graded as to the severity of pathological changes in the striatum. Marked significant reductions of SPLI were found in all striatal nuclei which were significantly correlated with the percentage of neuronal loss in the varying pathologic grades. Similar changes were found in the projection sites of striatal substance P neurons, the globus pallidus interna and the substantia nigra. These changes are consistent with a loss of striatal substance P containing projection neurons in HD. Significant reductions in SPLI were also found in the external pallidum, bed nucleus of the stria terminalis and the subthalamic nucleus. Small significant increases in SPLI (20-30%) were found in 3 frontal cortical regions (Brodmann areas 6, 8 and 9). The finding of neurochemical changes in the subthalamic nucleus is of particular interest since lesions in this nucleus are known to result in chorea and therefore might contribute to the chorea which is a cardinal symptom of HD.

Aged↗

PubMed1988

Hypophysiotrophic function of vasopressin and oxytocin.

We have investigated the effects of lesioning the hypothalamic paraventricular nucleus (PVN) on the secretion of two corticotropin-releasing neurohormones, vasopressin (VP) and oxytocin (OT), at the median eminence. The experimental model was the median eminence incubated in vitro, the secretion of neurohormones was stimulated by adding 48 mM KCl to the incubation medium. In addition, immunohistochemical staining was performed to correlate the changes in neuropeptide secretion with the distribution of VP and OT immunoreactive elements in the median eminence. Lesioning of the PVN abolished the KCl-induced release of VP 1 week after hypothalamic surgery. After a longer period of postoperative survival (6 weeks), VP release was restored towards normal. The secretion of OT was reduced by 50% at 1 week after lesioning and rose to 400% of control at six weeks. The changes in VP and OT release at the median eminence largely correlated with the immunohistochemical distribution of VP and OT immunopositive nerve fibers in the external zone of the median eminence. Most importantly, 6 weeks after the PVN lesion a dense network of OT immunoreactive varicosities was observed around primary portal capillaries, where normally OT fiber density is very low. These results demonstrate the functional and structural plasticity of VP- and OT-ergic neuronal systems that project to the median eminence. Furthermore, when taken together with earlier studies on the regulation of corticotropin secretion in long-term PVN-lesioned rats, the data indicate an important role for OT in the regulation of pituitary-adrenocortical function in PVN-lesioned rats.

Animals↗

PubMed1988

Galanin-like immunoreactivity is unchanged in Alzheimer's disease and Parkinson's disease dementia cerebral cortex.

Galanin is a recently isolated neuropeptide that is of particular interest in dementing disorders because of its known colocalization with choline acetyltransferase in magnocellular neurons of the basal nucleus of Meynert. These neurons degenerate in Alzheimer's disease, and there is a corresponding deficiency of cortical choline acetyltransferase activity. In the present study, galanin-like immunoreactivity was measured in the postmortem cerebral cortex and hippocampus of 10 controls and 14 patients who had had Alzheimer's disease. Significant reductions of choline acetyltransferase activity (50-60%) were found in all regions examined; however, there was no significant effect on concentrations of galanin-like immunoreactivity. Similar measurements were made in postmortem tissues of 12 control and 13 demented Parkinsonian patients who had had Alzheimer-type cortical pathology. Choline acetyltransferase activity was again significantly decreased in all regions examined but there were no significant reductions in galanin-like immunoreactivity. Experimental lesions of the fornix in rats produced parallel significantly correlated reductions of both choline acetyltransferase activity and galanin-like immunoreactivity in the hippocampus. Galanin-like immunoreactivity in the human hypothalamus consisted of two molecular-weight species on gel-permeation chromatography, and two forms were resolved by reverse-phase HPLC. The paradoxical preservation of galanin-like immunoreactivity, despite depletion of the activity of choline acetyltransferase, with which it is colocalized, is as yet unexplained. Recent studies have shown that galanin inhibits both acetylcholine release in the hippocampus and memory acquisition; therefore, preserved galanin may exacerbate the cholinergic and cognitive deficits that accompany dementia.

Aged↗

PubMed1987

The regional distribution of somatostatin and neuropeptide Y in control and Alzheimer's disease striatum.

Somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were measured in subdissections of both normal and Alzheimer's disease (AD) striatum at 5 coronal levels. Concentrations of both neuropeptides were relatively homogeneously distributed in the coronal and anterior-posterior planes except for a trend towards increased concentrations in the tail of the caudate and the posterior putamen. The nucleus accumbens showed 2-3-fold higher concentrations of both SLI and NPYLI than the rest of the striatum. There were no significant differences between control and AD brains. The high concentrations of SLI and NPYLI in the nucleus accumbens suggest that this region may receive somatostatin-neuropeptide Y afferents and that somatostatin and neuropeptide Y may play a role in the modulation of motor activity.

Adult↗

PubMed1987

A comparison of somatostatin and neuropeptide Y distribution in monkey brain.

The concentrations of both somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were measured in all major cortical and subcortical regions of monkey brain. High concentrations of both SLI and NPYLI were found in cerebral cortex where they were significantly correlated, supporting a colocalization of the two peptides in cortical neurons. There were no significant differences between the right and left hemispheres. Subdissections of the basal ganglia showed that concentrations of both SLI and NPYLI were 3-fold higher in the nucleus accumbens than in the remainder of the striatum, where concentrations of the peptides were evenly distributed. SLI and NPYLI levels were significantly correlated in the striatum, supporting a colocalization of the two neuropeptides in striatal neurons. Concentrations were low in the globus pallidus. Limbic system nuclei including the amygdala, bed nucleus of the stria terminalis and substantia innominata had relatively high concentrations of both SLI and NPYLI. In several subcortical regions concentrations of the neuropeptides were dissociated, suggesting separate neuronal populations. The distribution of both neuropeptides in monkey brain closely resembles that in human brain. The high levels in cerebral cortex and basal ganglia suggest that somatostatin and neuropeptide Y may play a role both in cognition and in normal motor function.

Amygdala↗

PubMed1987

Amino acid neurotransmitter abnormalities in Huntington's disease and the quinolinic acid animal model of Huntington's disease.

Concentrations of gamma-aminobutyric acid (GABA), glutamate, aspartate, and taurine were measured in postmortem tissue from the brains of patients with Huntington's disease (HD) and in the quinolinic acid (QA) lesioned rat striatum. The aim of the study was to assess further the ability of the QA model of HD to reproduce the neurochemical features of the disease. Nine cortical and 9 subcortical regions were examined from 17 pathologically graded cases of HD and 10 controls. Significant reductions in both GABA and glutamate were found in HD striatum. The reductions were greater in the more severely affected grades of HD, and there was a gradient of amino acid loss across the striatal nuclei (caudate greater than putamen greater than nucleus accumbens) which was consistent with the known pattern of pathological involvement. Taurine and aspartate concentrations showed no significant change. GABA reductions were found in both segments of the globus pallidus (external greater than internal) and both parts of the substantia nigra (reticulata greater than compacta). In advanced cases of HD, there were significant reductions in glutamate in Brodmann cortical areas 3-1-2, 6, 9, and 17, but GABA, aspartate, and taurine were unaltered in the cortex. The QA lesions reproduced the striatal deficits of both GABA and glutamate but, in contrast to HD, there was a decrease in taurine, possibly due to species differences. Chronic QA lesions resulted in a secondary dying back of corticostriatal glutamatergic terminals, but did not produce a change in cortical glutamate concentration. This suggests that reductions in cortical glutamate in HD may reflect a primary loss of glutamatergic neurons. Our findings extend previous observations on amino acid neurotransmitters in HD and, with the exception of taurine, confirm the general applicability of the QA model.

Amino Acids↗

PubMed1987

Oxytocin in Alzheimer's disease: postmortem brain levels.

Oxytocin (OXY) injected into the hippocampus is reported to interfere with the formation of memory in experimental animals. Memory impairment is one of the distinguishing features of Alzheimer's disease. We have studied OXY immunoreactivity in postmortem brain tissue from 12 cases of histologically confirmed Alzheimer's disease and 13 controls. OXY concentration was increased 33% in the hippocampus and temporal cortex of Alzheimer brains (p less than 0.05), but normal in all other regions examined. Elevated hippocampal OXY levels may contribute to the memory disturbance associated with Alzheimer's disease.

Adult↗

PubMed1987

Substance P-like immunoreactivity is reduced in Alzheimer's disease cerebral cortex.

Substance P is an undecapeptide which has been found in human cortical neurons. We measured concentrations of this peptide in Alzheimer's disease (AD) and control postmortem tissue by radioimmunoassay. Using high-performance liquid chromatography, most of the immunoreactivity from AD or control temporal cortex comigrated with synthetic standards. Significant reductions of 20 to 40% in substance P-like immunoreactivity were found in AD cerebral cortex and hippocampus, most severe in the inferior temporal gyrus. Substance P neurons or their terminals are vulnerable to the pathophysiologic process in AD.

Aged↗

PubMed1987

Neuropeptides in Alzheimer's disease.

A large number of neuropeptides have been found in cortical neurons. They are therefore of interest in attempting to demonstrate selective vulnerability of different populations of neurons in Alzheimer's disease (AD). The most consistent neuropeptide deficit in AD is reductions in cortical concentrations of somatostatin. Lesser reductions in corticotropin-releasing factor, neuropeptide Y and substance P have been reported. Concentrations of both vasoactive intestinal polypeptide and cholecystokinin are relatively preserve. The morphologic correlate of reduced somatostatin concentrations in AD appears to be markedly distorted and reduced terminal fiber plexuses, rather than reduced numbers of neuronal perikarya. A large number of neuropeptides have been localized in senile plaques.

Alzheimer Disease↗

PubMed1986

Somatostatin immunoreactivity is reduced in Parkinson's disease dementia with Alzheimer's changes.

Somatostatin-like immunoreactivity (SLI) was measured in postmortem brain tissue from 15 control patients, 7 non-demented parkinsonian patients and 7 demented parkinsonian patients who had Alzheimer-type cortical pathology. The non-demented parkinsonian patients had normal concentrations of SLI in the cerebral cortex, hippocampus, amygdala, putamen, caudate or globus pallidus. Demented parkinsonian patients with Alzheimer-type cortical pathology had significantly reduced (approximately 40%) levels of SLI in both the frontal (Brodmann area 6) and temporal (Brodmann area 21) cortex. These findings suggest that parkinsonian dementia with Alzheimer-type pathology like Alzheimer's disease itself, is associated with reduced concentrations of cortical somatostatin.

Adult↗

PubMed1986

Reduced concentrations of arginine vasopressin and MHPG in lumbar CSF of patients with Korsakoff's psychosis.

The concentrations of arginine vasopressin (AVP), somatostatin (SS), and the primary brain metabolites of norepinephrine (MHPG), serotonin (5-HIAA), and dopamine (HVA) were measured in samples of lumbar CSF obtained from ten amnesics with Korsakoff's psychosis, four patients with a history of Korsakoff's psychosis who had recovered from the amnesic symptoms of this disease, and control subjects. Significant deficits were observed in the amnesic group for AVP and MHPG, but not for the other substances measured. Subjects who had recovered from the amnesic symptoms of Korsakoff's psychosis had increased concentrations of AVP and MHPG, but not of SS or the other monoamine metabolites.

Adult↗

PubMed1986

Somatostatin-28(1-12)-like immunoreactivity is reduced in Alzheimer's disease cerebral cortex.

A deficiency in somatostatin is the most consistently described neurochemical alteration in Alzheimer's disease (AD) attributable to intrinsic cortical neurons. Somatostatin-28 (SOM-28), an N-terminal-extended form of somatostatin, can be cleaved to form somatostatin-28(1-12)(SOM-28(1-12) ) and somatostatin-14 (SOM-14). We have measured concentrations of SOM-28(1-12)-like immunoreactivity in 8 cortical regions from 12 patients with AD and 13 controls. Significant reductions (P less than 0.001) were found in all cortical regions examined with the largest decrease in temporal lobe. Reductions were significantly correlated with decreases in somatostatin-14-like immunoreactivity in the same regions. The similar reductions of two prosomatostatin-derived peptides in AD cerebral cortex supports the contention that decreased somatostatin immunoreactivity in AD is caused by a degeneration of somatostatin cortical neurons and terminals.

Aged↗

PubMed1986

An examination of neuropeptide Y postmortem stability in an animal model simulating human autopsy conditions.

A rabbit antiserum to neuropeptide Y (NPY) was used to develop a radioimmunoassay for measuring NPY in brain tissue. By high-performance liquid chromatography, two peaks of immunoreactivity were detected in human postmortem cortex. A minor peak was seen at the void volume, while the majority of immunoreactivity comigrated with synthetic NPY standards. Using the Spokes-Koch rat model simulating human autopsy conditions, it was shown that cortical, hippocampal and striatal concentrations of NPY-like immunoreactivity are stable for up to 24 h.

Animals↗

PubMed1986

Neuropeptide Y immunoreactivity is reduced in cerebral cortex in Alzheimer's disease.

Neuropeptide Y is a 36-amino acid peptide that is found in high concentrations in cerebral cortex and is contained in cortical neurons. We measured concentrations of this peptide in postmortem tissue from patients with Alzheimer's disease and controls using a sensitive and specific radioimmunoassay. High-performance liquid chromatography showed that more than 95% of immunoreactivity co-migrated with synthetic standards in both Alzheimer's disease and control frontal cortex. Significant reductions in neuropeptide Y-like immunoreactivity were found in eleven cortical regions, the hippocampus, and the locus ceruleus. The regions particularly affected included the temporal lobe, frontal lobe, and occipital cortex. As neuropeptide Y is co-localized with somatostatin in a considerable proportion of cortical neurons, the loss of immunoreactivity may in part reflect degeneration of these neurons. Further study of the selective vulnerability of these neurons in Alzheimer's disease cortex may provide clues to the nature of the underlying disease process.

Aged↗

PubMed1986

Widespread reduction of somatostatin-like immunoreactivity in the cerebral cortex in Alzheimer's disease.

Although several studies have documented reduced concentrations of somatostatin-like immunoreactivity (SLI) in the cerebral cortex in Alzheimer's disease, there is controversy concerning the extent and importance of these changes. We measured SLI in brains obtained post mortem from 12 patients with pathologically confirmed Alzheimer's disease and from 13 neurologically normal controls. All major cortical and subcortical regions were examined. Widespread reductions of SLI in Alzheimer's disease cerebral cortex were found, with the most profound changes seen in temporal lobe; but there also were major reductions in both the frontal and occipital cortex. There were no significant reductions in subcortical regions. Characterization of SLI by high-pressure liquid chromatography showed no significant difference in profiles between Alzheimer's disease and control frontal cortex. These results suggest that the reduction in somatostatin immunoreactivity in Alzheimer's disease may be caused by degeneration of intrinsic somatostatin cortical neurons.

Acetylcholinesterase↗

PubMed1986

A postmortem study of amino acid neurotransmitters in Alzheimer's disease.

Concentrations of putative neurotransmitter amino acids were measured in postmortem brains from 10 patients with Alzheimer's disease and 10 controls. Glutamate, aspartate, taurine, gamma-aminobutyric acid (GABA), and alanine levels were examined in 9 cortical regions, hippocampus, thalamus, and basal ganglia using high-performance liquid chromatography with electrochemical detection. There were no significant alterations in aspartate, taurine, or alanine levels in any of the regions examined. Widespread significant reductions in cortical GABA concentrations were observed in the Alzheimer's brains, with the largest decreases in the temporal lobe. Overall values for glutamate concentrations in temporal and frontal cortices showed a significant 12% reduction in Alzheimer's brains, but the only individual cortical region showing a significant reduction in glutamate was the inferior temporal gyrus. These results suggest that gamma-aminobutyric acidergic neurons in Alzheimer's cerebral cortex may be selectively vulnerable to the disease process.

Aged↗