The hypothalamic hormone oxytocin: from gene expression to signal transduction.
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Animals↗
Biomedical subjects
E Mohr
Publications and source records attributed to E Mohr.
Statistical analysis of the incidence of positives in the examination of parasitological specimens.
Results of the examination of 2,000 parasitological specimens were analyzed for differences between results obtained by a technologist working in parasitology only and those obtained by general microbiologists who were also performing other laboratory work. The relative share of specimens determined to be positive by the specialist was approximately twice as high as the relative share determined by the general microbiologists.
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Heterogeneity in Alzheimer's disease: progression rate segregated by distinct neuropsychological and cerebral metabolic profiles.
In an attempt to define possible subgroups of Alzheimer's disease, 21 patients satisfying current clinical diagnostic criteria for this disorder were divided on the basis of progression rates of symptoms. Thirteen patients with relatively rapid intellectual deterioration did not differ from eight patients showing slow progression with respect to global intellectual performance, sex, or age at onset of symptoms. Neuropsychological testing revealed that although the two groups were indistinguishable in verbal or visuospatial functions associated with the parietotemporal cortex, the more rapidly deteriorating group had significantly greater impairment in executive functions attributed to the frontal lobe. PET scans showed equivalent reductions in glucose metabolism in the parietotemporal cortex, but patients with relatively fast progression had significantly greater hypometabolism frontally. These results suggest an association between relatively severe frontal lobe involvement and a rapid clinical course that might have important implications for the development of treatment strategies for patients with Alzheimer's disease.
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Deprenyl in Parkinson's disease: mechanisms, neuroprotective effect, indications and adverse effects.
Deprenyl is a synthetic, selective inhibitor of the monoamine oxidase-B enzyme system. The mechanism of its beneficial effect in early and advanced Parkinson's disease is not settled. Increased striatal dopamine accumulation, sensitization of surviving dopamine neurons with increased dopamine production and reduced nigro-striatal toxicity may all contribute. The standard daily dose of deprenyl is 10 mg. Selectivity may be lost at higher doses. Deprenyl is especially indicated in untreated patients, improving up to 50 percent of patients with mild motor fluctuations. Major symptomatic benefit also occurs in occasional levodopa treated patients. Adverse effects are common, however. Increase dyskinesias, confusion and hallucinations, nausea and postural hypotension may necessitate drug withdrawal or the use of low dose regimens. Caution should be exercised with older patients, those with ulcer disease, which may be worsened by deprenyl, and individuals with active ischemic heart disease where the safety of this drug is not yet clear.
Humans↗
[Evaluation of the postoperative "state of health" using the example of the body core temperature rhythms of sheep].
A postoperative (p.op.) estimation of "healthiness"--especially an estimation of duration of possible existing changes, caused by surgical treatment--is important not only for the ongoing of the healing up process. A re-activation of treated farm or laboratory animals which is set up too early might produce reduction of efficiency or falsification of experimental results. Investigations on p.op. de-synchronisation have proved that "healthiness" means--besides the absence of clinical symptoms--also stable relations among the circadian rhythms. As the ultradian rhythms (wavelength less than 24 h) which exist beside the circadian ones depend on endogenic and exogenic factors much more than the circadian rhythms do, the aim of this study was to investigate strength and especially duration of changes p.op. in using core temperature rhythms of sheep as example, by setting great value on investigating ultradian rhythms. The core temperatures of 5 Merino-mixed sheep were permanently measured for 4 weeks p.op. by special radiotelemetric equipment, under controlled circumstances. All recorded data have been expertised "macroscopically" and Fourier-analysis was employed for judging phase shift and intensity of existing rhythms. Though no signs for systemic disturbances could be found and the recorded temperature always was in between the physiological range, important shifts of phases and variations in intensities in the ultradian scope as well as in the circadian one occurred. The "normal" or final phase relations and the constant daily pattern of intensities in sheep were reached 16 days p.op. earliest.
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[Recording the feeding behavior of freely moving animals using the example of freely diving Weddell seals (Leptonychotes weddellii)].
During the antarctic summer 1990, the pattern of food intake in comparison to diving-activity was investigated on adult Weddell seals. Diving depths were recorded by a time-depth recorder (TDR). The TDR is a free programmable electronic datalogger, which can store data on up to 5 channels. It was fixed on the fur of the seal, ensuring that no longer lasting irritation of the animal was caused. The pattern of food-intake was monitored by measuring the jaw-movements, using strain gauges for recording the deformation of the muscles by mastication. After electronic amplification and filtering, the frequency of jaw-activity within a measuring period was recorded one channel of the TDR. By simultaneously observing the diving depths, these data may lead to conclusions about chewing patterns of the seal in water depths where they catch prey. The graph of these data and the mathematical evaluation by Fourier analysis and Plexogramme show a close correlation between diving depth and jaw-activity.
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Neuropsychological and glucose metabolic profiles in asymmetric Parkinson's disease.
Patients with predominantly unilateral parkinsonian signs may provide a unique opportunity to evaluate the cerebral representation of cognitive functions characteristically affected in idiopathic Parkinson's disease. Twenty hemiparkinsonian patients (ten left and ten right) and 10 healthy controls, matched for age and education, were studied with neuropsychological tests and positron emission tomography. Both right and left hemiparkinsonians evidenced impairments in visuospatial and verbal episodic memory function, but had no deficits in executive abilities, compared to controls. None of the neuropsychological test scores distinguished right from left hemiparkinsonians. Glucose metabolic profiles were identical for the three groups in all cortical areas assessed; in the subcortex however, lenticular hypermetabolism contralateral to the predominant side of motor involvement was evident in the left hemiparkinsonian group. Correlational analysis revealed that higher glucose metabolic rates in the basal ganglia of these hemiparkinsonians were associated with lower visuospatial test scores. In frontal and parietal cortex, decreasing glucose metabolism was positively associated with neurobehavioral function; in temporal cortex, measures of attention and memory decreased with increasing glucose metabolic rates.
Adult↗
Axonal transport of neuropeptide encoding mRNAs within the hypothalamo-hypophyseal tract of rats.
Hypothalamic vasopressin and oxytocin transcripts have been detected in the posterior pituitary suggesting either transcription of the respective genes in pituicytes or axonal mRNA transport from the hypothalamus to the nerve terminals of the posterior pituitary. The concept of axonal mRNA transport is supported firstly, by Northern blot and in situ hybridization analysis indicating that vasopressin and oxytocin mRNAs are also present in the neural stalk; secondly, by intron analysis and transcription run on experiments demonstrating the absence of primary vasopressin and oxytocin transcripts in non-neuronal cells of the posterior pituitary; thirdly, by embryonic developmental studies showing that appearance of vasopressin transcripts in the hypothalamus and the pituitary anlage is correlated. Furthermore, during axonal transport the respective mRNAs are subject to specific modification at the poly(A) tails.
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Visuospatial cognition in Huntington's disease.
The notion of specificity of visuospatial dysfunction in Huntington's disease (HD) was evaluated in a sample of afflicted patients as a function of symptom duration, age at onset, and overall dementia severity. Factor analytic procedures indicated that overall visuospatial processing capacity (factor 1) as well as the ability for spatial manipulation (factor 3) was markedly affected in HD patients. In contrast, consistency of spatial judgment (factor 2) appeared to remain relatively intact in these patients. Age at onset seemed to have no relationship with any of these variables, whereas dementia severity demonstrated a significant relationship with overall visuospatial processing capacity. Most importantly, duration of symptoms was significantly associated with the declining ability to mentally perform spatial manipulations. The observation of circumscribed visuospatial impairment in HD patients may have important consequences for the further understanding of the neurobehavioral consequences of this disorder.
Adult↗
Functional characterization of estrogen and glucocorticoid responsive elements in the rat oxytocin gene.
Expression of the gene encoding the oxytocin precursor occurs in the hypothalamus and, to a lesser extent, in a number of peripheral organs, the tissue-specific regulatory mechanisms of which are largely unknown. By DNA sequence analysis several elements upstream of the transcriptional start point of the rat oxytocin gene were identified matching the consensus sequence of enhancers inducible by estrogen or glucocorticoids, respectively. Their general transactivating capacities were investigated using heterologous gene constructs and revealed that the rat oxytocin gene harbours two functional estrogen responsive elements near the transcription initiation site, one of which is conserved in the respective human gene. In addition, one enhancer conferring glucocorticoid responsiveness to a reporter gene is located at nucleotide residues -2449 to -2464. These data might indicate a steroid hormone-mediated influence on oxytocin gene expression in the central nervous system and/or the periphery.
Animals↗
Rat vasopressin and oxytocin genes are linked by a long interspersed repeated DNA element (LINE): sequence and transcriptional analysis of LINE.
Sequence analysis of the rat vasopressin and oxytocin gene family reveals that the two genes are linked by a long interspersed repeated DNA element (LINE) giving rise to seven long open reading frames encoding hypothetical proteins of 99 to 556 amino acid residues. Furthermore, although both DNA strands of LINEs serve as templates for transcription, transcripts initiated at the 3' end are more abundant than those started from the 5' end. The LINEs are transcribed preferentially in brain tissues as analyzed by Northern blot, in situ hybridization, and RNase protection experiments. The data show that most LINEs are transcribed at their entire length and that a major fraction of respective RNAs does not enter the cytoplasm but remains in the cell nucleus.
Amino Acid Sequence↗
Differential memory and executive functions in demented patients with Parkinson's and Alzheimer's disease.
Selected aspects of verbal memory and executive function were compared in 11 demented Parkinson's disease (PD) patients and 11 Alzheimer's disease (AD) patients with equally severe dementia, with 11 healthy controls matched for age and education. Semantic and episodic memory were impared in all patients compared with controls, but to a relatively greater degree in AD patients than in those with PD. In contrast, demented PD patients were relatively more compromised on executive tasks. These findings, taken in the context of the neuropathological and neurochemical overlap between demented PD and AD patients, suggest that differences in neurobehavioural patterns in patients with these diseases are relative, rather than absolute.
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Nootropic drugs in Alzheimer's disease: symptomatic treatment with pramiracetam.
The cognitive-enhancing effects of pramiracetam in animal models of learning and memory are characterized by an inverted U-shaped dose-response curve. We evaluated antidementia efficacy of this drug in 10 patients with probable Alzheimer's disease employing a 2-phase, placebo-controlled, enrichment-type trial design. Eight patients evidenced a best dose in the dose-finding phase, but in the subsequent replication phase only two again improved to a similar degree. PETs with fluorodeoxyglucose obtained in two individuals showed no definite change. Doses up to 4,000 mg pramiracetam are unlikely to confer symptomatic benefit to Alzheimer's disease patients.
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Clinical trials in dementia: learning effects with repeated testing.
The possible confounding role of learning effects during multiple test administration in clinical trials in demented subjects remains uncertain. Seventeen mildly to severely affected patients with Alzheimer's disease (AD) and 16 controls were evaluated with an extensive neuropsychological battery of manually administered and computerized tests. Subjects received 3 weekly sessions using alternate test forms, to mimic a baseline, placebo, and drug condition. Mean scores of AD patients as a group showed no stable improvement, but more subtle learning effects were suggested by an association of dementia severity and change scores in verbal and visual learning. Controls evidenced consistent learning in 3 of 9 tests. These results suggest that clinical trials data from AD patients, especially those with moderately severe impairment, are not contaminated by learning. Degree of cognitive impairment may be related to learning capacity, suggesting caution for learning effects in controls and possibly in patients with mild AD.
Aged↗
Rats with physically disconnected hypothalamo-pituitary tracts no longer contain vasopressin-oxytocin gene transcripts in the posterior pituitary lobe.
In rats, vasopressin- and oxytocin-encoding mRNAs are present in the posterior but absent in the anterior lobe of the pituitary gland. RNase protection experiments indicate that in the posterior pituitary and hypothalamus identical transcriptional start points are used. Furthermore, the two transcripts from posterior pituitary and hypothalamus show identical nucleotide sequences. Animals operated by paired electrical lesions in such a way that connections between the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus and the posterior pituitary lobe are destroyed continue to express the vasopressin and oxytocin gene in the hypothalamus but not in the posterior pituitary. Operated animals subjected to chronic intermittent salt loading for 6 days similarly contain vasopressin and oxytocin encoding transcripts in the hypothalamus but not in the posterior pituitary.
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Sequence analysis of the promoter region of the rat vasopressin gene.
The vasopressin gene is highly transcribed in magnocellular neurons of the supraoptic (SON) and paraventricular nucleus (PVN) in the rat hypothalamus. In order to identify cis-acting elements involved in the expression of the vasopressin gene, approximately 1 kb upstream of the transcription start site has been sequenced. Several putative regulatory elements have been detected, including a glucocorticoid response element (CRE), a cAMP response element (CRE), and four AP2 binding sites. In gel shift assays performed with a labelled DNA fragment corresponding to nucleotide residues -214 to -36 and nuclear proteins extracted from SON-derived tissue enriched in magnocellular neurons, three specific protein-DNA complexes have been detected. Complex formation is effectively competed by addition of an excess of unlabelled fragment.
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Regional cerebral blood flow and cognitive function in Huntington's disease and schizophrenia. A comparison of patients matched for performance on a prefrontal-type task.
Matching patients with etiologically distinct but clinically overlapping cognitive disorders on performance of a regionally specific neuropsychological task is a novel and potentially powerful approach to highlighting differences in the pathophysiological mechanisms of impaired cognition. We used this strategy to compare patients with Huntington's disease (HD) and schizophrenia (SC), disorders that share similarities in cognitive impairment. Patients were matched on the basis of performance on the Wisconsin Card Sorting test of "prefrontal" function, after which neuropsychological test data and regional cerebral blood flow data were determined while patients who performed the Wisconsin Card Sorting test were examined. Patients with HD performed worse on visuospatial tasks and recall memory than did patients with SC, although Wechsler Adult Intelligence Scales-Revised IQ and Wechsler Memory Scale memory quotients were equivalent. These differences could not be attributed to differences on the index task, the Wisconsin Card Sorting Test. Patients with HD and SC exhibited a double dissociation in regional cerebral blood flow. The patients with SC had relatively low frontal and high parietal flows, while patients with HD exhibited the reverse of this pattern. Thus, the regional cerebral blood flow and neuropsychological findings in this study appeared to demonstrate that the single final common cognitive impairment of executive function in HD and SC is associated with two markedly dissimilar pathophysiological states.
Adult↗
Variations of core-temperature rhythms in unrestrained sheep.
Variations of core-temperature rhythms occurring during a "normal" day (24-hour period without extraordinary challenges for organism) were studied in 5 male sheep. To record the influence of the metabolic processes in different organic systems, core temperatures were measured at various locations at the same time. To minimise any influences due to measurement or behavior (e.g., effects of isolation), a telemetric system was used for registration and animals were kept without restraint in their habitual herd. Particularly biphasic circadian rhythms were found, and feeding schedule as zeitgeber is discussed. Beyond that, independent from point of measurement short-time rhythms with wavelengths of 140 and 90 min were found. Therefore, an origin in the central nervous system can be supposed. Rhythms with wavelengths of 3 hours, 75 min and 1 hour were not stable throughout a whole 24-hour period and did not occur at all measurement points in the same intensity. A comparison of anatomical placements of the various measurement points leads to the realization of distinct organic functions as sources for these rhythms.
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