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.

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.

Cerebrospinal fluid somatostatin and neuropeptide Y. Concentrations in aging and in dementia of the Alzheimer type with and without extrapyramidal signs.

Cerebrospinal fluid somatostatin and neuropeptide Y concentrations were measured in 26 healthy normal subjects, 27 patients with dementia of the Alzheimer type (DAT), and seven patients with DAT with extrapyramidal signs (EDAT). In healthy normal subjects, there was no significant correlation between age and either somatostatin or neuropeptide Y concentration. However, the concentrations of both peptides correlated significantly with each other.

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.

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.

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.

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.

[Effect of the treatment with adrenocorticotropic hormone on the 2,3-diphosphoglycerate level in the erythrocytes of patients with multiple sclerosis].

The reported study was carried out in 20 patients with multiple sclerosis (12 women, 8 men) aged 23 to 54 years, with disease duration from 3 to 20 years. The patients were treated with the preparation ACTH-Polfa 2000 mg for one treatment course. The patients were divided into subgroups considering the age, disease duration, clinical form and clinical course of the disease.

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.

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.

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.

Anticonvulsant evaluation of some 3-oxo and 3-thiosemicarbazono analogues of 1-aryl-1-ethylthio-nonanes and related compounds.

A number of 3-oxo and 3-thiosemicarbazono analogues of 1-aryl-1-ethylthio-nonanes and related compounds were synthesized. Solutions of the thiosemicarbazones in deuterochloroform were shown by PMR spectroscopy to exist principally in the anti configuration at equilibria except when an ortho-methoxy group was present in the aryl ring. In this case intramolecular hydrogen bonding probably accounts principally for the presence of equal amounts of anti and syn isomers.

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.

Vasopressin in Alzheimer's disease: a study of postmortem brain concentrations.

Vasopressin (AVP) and its analogues are reported to improve learning- and memory-related performance in experimental animals, and perhaps also in humans. Memory impairment is a clinical hallmark of the dementing disorder, Alzheimer's disease. We have examined AVP concentrations in postmortem brain tissue from 12 patients with histologically confirmed Alzheimer's disease and 13 control subjects.

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.

Neuropeptides in Alzheimer's disease. Clinical implications.

Since the isolation and sequencing of the enkephalins in the mid-1970s, there has been an explosion of knowledge concerning putative peptide neurotransmitters in the brain. This article focuses on selected developments in neuropeptide research that may have bearing on our understanding of and clinical approach to the dementing degenerative disorder Alzheimer's disease (AD), a cardinal feature of which is impairment of memory.

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 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.

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.

CSF vasopressin concentration is reduced in Alzheimer's disease.

The concentration of arginine vasopressin (AVP) was measured in cerebrospinal fluid (CSF) by radioimmunoassay. Serial dilution curves and reversed-phase high-pressure liquid chromatography (HPLC) showed that the material measured behaved identically to authentic vasopressin. Levels of CSF AVP were reduced by 37% in Alzheimer's disease, but were normal in Huntington's disease, normal-pressure hydrocephalus, and several other neurologic disorders.

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.

Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid.

Huntington's disease (HD) is an autosomal dominant neurological disorder characterized by progressive chorea, cognitive impairment and emotional disturbance. The disease usually occurs in midlife and symptoms progress inexorably to mental and physical incapacitation. It has been postulated that an excitotoxin is involved in the pathogenesis of HD.

Alpha 1-adrenergic receptor activation releases vasopressin and oxytocin from perfused rat hypothalamic explants.

Norepinephrine and the alpha-agonist phenylephrine in concentrations of 10(-5) to 10(-3) M prompted the release of radioimmunoassayable vasopressin (up to 150 pg/min) and oxytocin (up to 20 pg/min) from intraarterially perfused explants of rat basal forebrain. Drug effects were markedly reduced or abolished in the presence of the non-specific alpha-antagonists phentolamine and phenoxybenzamine, and the specific alpha 1-antagonist prazosin. In concert with recent in vivo and in vitro electrophysiological observations, these data imply that endogenous noradrenergic pathways to magnocellular neurosecretory cells are excitatory, mediated through activation of their alpha 1-receptors, thereby enhancing the release of both vasopressin and oxytocin in the neurohypophysis.