Biomedical subjects

S Steinlechner

Publications and source records attributed to S Steinlechner.

At least 19 recordsLinked to original sources

PubMed2006

Morphological basis for the spectrum of clinical deficits in spinocerebellar ataxia 17 (SCA17).

Spinocerebellar ataxia 17 (SCA17) is a rare genetic disorder characterized by cerebellar, extrapyramidal, pyramidal as well as psychiatric signs. The pathoanatomical basis of this disorder is still not well known. A total of 12 patients and 12 age- and sex-matched controls were examined by in vivo MRI voxel-based morphometry (VBM). Besides general patterns of disease-related brain atrophy, characteristic syndrome-related morphological changes in SCA17 patients were studied. In comparison with normal controls, SCA17 patients showed a pattern of degeneration of the grey matter centred around mesial cerebellar structures, occipito-parietal structures, the anterior putamen bilaterally, the thalamus and other parts of the motor network, reflecting the cerebellar, pyramidal and extrapyramidal signs. A correlation analysis revealed a clear association between the clinical cerebellar, extrapyramidal and psychiatric scores and degeneration in specific areas. Two degeneration patterns were found as follows: regarding motor dysfunction, atrophy of the grey matter involved mainly the cerebellum and other motor networks, in particular the basal ganglia. In contrast, correlations with psychiatric scores revealed grey matter degeneration patterns in the frontal and temporal lobe, the cuneus and cingulum. Most interestingly, there was a highly significant correlation between the clinical Mini-Mental State Examination scores and atrophy of the nucleus accumbens, probably accounting for the leading psychiatric signs.

Adult↗

PubMed2006

Stress-induced hyperthermia in the rat: comparison of classical and novel recording methods.

Stress causes a rise in body temperature in laboratory animals (stress-induced hyperthermia). However, the direct effect of common stressors in animal research, i.e. transportation between holding and test rooms or isolation of animals, on body temperature has not been investigated to its full extent. To address this question, it is important to have a reliable and simple monitoring technique, which does not induce stress itself. In the present study, we investigated stress-related changes in body temperature of F344/Hw rats after (1) moving the cage within the holding room, (2) moving the cage from the holding room to another test room and (3) social deprivation (isolation). A combination of two different body temperature recording methods was used to clarify their accuracy and stress-inductive character: rectal temperature recording and peritoneal implanted temperature sensors (Thermochron iButtons).The results demonstrate that (1) different stressors induce a significant rise in body temperature, (2) which is detectable for more than 60 min and (3) it is of importance to standardize temperature recording methods in order to avoid confounding effects of the recording method itself. Furthermore, Thermochron iButtons are more accurate and reliable for body temperature studies than rectal recordings.

Animals↗

PubMed2005

[Treatment of sialorrhea with botulinum toxin: an overview].

Hypersalivation (sialorrhea) is a common complaint of patients with neurodegenerative disorders such as Parkinson's disease or amyotrophic lateral sclerosis and a frequently disabling side effect of atypical antipsychotic drugs. Conventional treatment including oral anticholinergic or antihistamine medication is often limited by adverse effects and lack of efficacy. Over the past few years, several studies reported decreased drooling after injections of botulinum toxin into the salivary glands. This review describes the current state of treatment of sialorrhea with botulinum toxin.

Botulinum Toxins↗

PubMed2001

Evidence for microvesicular storage and release of glycine in rodent pinealocytes.

Prompted by previous studies suggesting a regulatory role for the inhibitory amino acid gamma-aminobutyric acid (GABA) within the mammalian pineal gland, we carried out a study of rat and gerbil pineal organs to elucidate whether there is evidence for a vesicular storage and release of GABA and/or glycine. Immunohistochemistry revealed the presence of the vesicular inhibitory amino acid transporter in pinealocytes. Moreover, we found that, in addition to glutamate and aspartate, cultured pinealocytes also released glycine upon stimulation by depolarizing concentrations of KCl, whereas the content of GABA in the culture medium did not exceed the detection limit either under control conditions or following KCl application. Therefore, we propose that glycine is a further component of the paracrine signaling system within the pineal organ which is based on the compartment of synaptic-like microvesicles (SLMVs) inside pinealocytes.

Amino Acid Transport Systems↗

PubMed1999

Interstrain differences in activity pattern, pineal function, and SCN melatonin receptor density of rats.

We investigated the possibility that strain-dependent differences in the diurnal pattern of wheel running activity rhythms are also reflected in the melatonin profiles. The inbred rat strains ACI/Ztm, BH/Ztm, and LEW/Ztm. LEW were examined for diurnal [12:12-h light-dark (LD)] wheel running activity, urinary 6-sulphatoxymelatonin (aMT6s) excretion, melatonin concentrations of plasma and pineal glands, and melatonin receptor density in the suprachiasmatic nuclei (SCN). ACI rats displayed unimodal activity patterns with a high level of activity, whereas BH and LEW rats showed multimodal activity patterns with ultradian components and reduced activity levels. In contrast, the individual daily profiles of aMT6s excretion and mean melatonin synthesis followed a unimodal time pattern in all three strains, suggesting that different output pathways of the SCN are responsible for the temporal organization of locomotor activity and pineal melatonin synthesis. In addition, melatonin synthesis at night and SCN melatonin receptor density at day were significantly higher in BH and LEW rats than in ACI rats. These results support the hypothesis of a long-term stimulating effect of melatonin on its own receptor density in the SCN.

Animals↗

PubMed1997

Expression of synaptic membrane proteins in gerbil pinealocytes in primary culture.

Pinealocytes of various mammalian species contain abundant synaptic-like microvesicles (SLMVs) which are considered the endocrine equivalent of neuronal synaptic vesicles. Although the pinealocytes may thus be a suitable cellular model for experimental in vitro studies of SLMVs, nothing is known about the presence of SLMVs in isolated pinealocytes maintained under tissue culture conditions. In the present investigation, we prepared dissociated primary cultures of gerbil pinealocytes to study the expression and distribution of protein components of synaptic vesicles/SLMVs and the presynaptic plasmalemma in pinealocytes kept in vitro. Using immunofluorescence microscopy, we found that cultured pinealocytes readily expressed all synaptic membrane proteins investigated, i.e., synaptophysin, synaptotagmin I, synaptobrevin II, syntaxin I and SNAP-25. Punctuate immunoreactivity for the vesicle-associated proteins could be detected throughout the cell bodies of pinealocytes and was also distributed into all of their processes which began to develop within the first days in culture. Outgrowing processes exhibited growth cone-like structures which were enriched in synaptic vesicle-associated proteins. After 1 week in vitro, pinealocytes had frequently formed an elaborate network of long interwoven processes. Accumulations of synaptic vesicle-associated proteins were observed in varicosities and terminal swellings of the processes. The vesicle-rich process swellings often established synaptic-like process swellings often established synaptic-like contacts with somata and processes of other pinealocytes. Some of the pinealocyte processes possessed additional axon-like properties as demonstrated by their lack of immunoreactivity for the somato-dendritic marker MAP2 and the transferrin receptor. The comparison of the staining patterns for synaptophysin and the endocytotic marker transferrin receptor by confocal laser scanning microscopy revealed a largely differential intracellular distribution of the two proteins. This may indicate that a substantial fraction of pinealocyte SLMVs by-passes the early endosomal-related recycling pathway of SLMVs. Herewith, we have shown that isolated gerbil pinealocytes maintained in primary culture can acquire morphological and neurochemical traits which closely mimick those observed in vivo. In particular, these cultures permit experimental studies of the compartment of pinealocyte SLMVs which seem to make up a major secretory pathway for paracrine intrapineal communication.

Animals↗

PubMed1997

Creatinine is an appropriate reference for urinary sulphatoxymelatonin of laboratory animals and humans.

In our studies on diurnal 6-sulphatoxymelatonin (aMT6s) rhythms in various species, we have sometimes obtained fluctuating patterns. In most of these, the volume of individual urine fractions was not accurately measured because of methodological problems. Here, we report a simple method to overcome these problems by using urinary creatinine to estimate urine volume. The benefit of this method is demonstrated in two representative examples of the diurnal aMT6s rhythms of rats, domestic pigs and humans. Because the human urine fractions were collected accurately, the qualitative pattern of the aMT6s rhythm was not altered by using urinary creatinine as a substitute for urine volume. The total creatinine excretion (urine volume x creatinine concentration) was constant within a small range and showed no diurnal rhythm. In rats and pigs, the highly variable aMT6s concentrations relative to urine volume throughout the 24-hr period were changed drastically by referring to creatinine. All aMT6s patterns became stable and qualitatively similar to those of the rest of the group. From these results it can be concluded that creatinine is an adequate substitute for urine volume and a beneficial parameter with which to overcome technical problems with urine collection from laboratory animals or unknown urine volumes in human studies.

Adult↗

PubMed1996

6-Sulphatoxymelatonin secretion in different locomotor activity types of the blind mole rat Spalax ehrenbergi.

6-Sulphatoxymelatonin (aMT6S) excretion was examined in the urine of rhythmic and arrhythmic blind subterranean mole rats (Spalax ehrenbergi) to test the correlation between melatonin secretion (as represented by aMT6S) and variability in circadian locomotor activity. Activity pattern was tested in four males, first for a week under short photoperiod [light:dark (LD) 10:14], followed by 10 days in constant darkness (DD). After several months the experiment was repeated under long photoperiod (LD 14:10), followed by DD conditions. Under LD conditions all animals exhibited aMT6S excretion during the dark phase, with a decline just before the onset of light. No correlation was found between activity pattern and melatonin secretion. The animal with the highest melatonin secretion both under LD and DD had an arrhythmic locomotor pattern. The results suggest that in mole rats melatonin secretion and circadian locomotor activity are controlled by two different mechanisms. There were large differences in the aMT6S levels among individuals, suggesting the importance of duration of melatonin secretion over amplitude for gonadal development and thermoregulatory changes. During summer, i.e., before the breeding season, the animals keep a more stable aMT6S secretion than in winter, and the amplitude of secretion is higher under DD vs. LD conditions.

Activity Cycles↗

PubMed1996

Melatonin as a chronobiotic: PROS and CONS.

The pineal gland is a major component in the regulation of photoperiodic responses and hence, saisonality. All functions which appear to be controlled by the daylength can be influenced by modifying the output signal of the pineal gland, i.e. melatonin. An important property of the melatonin signal is that the duration of melatonin synthesis and release varies proportionally with the length of the night suggesting that the duration of elevated melatonin is the most important signal conveying the photoperiodic message. In addition to the temporal coordination of saisonal phenomena, melatonin appears to be involved in the control of circadian rhythms in mammals. Activity-rest cycles of rats can be entrained by infusion or injection of melatonin at appropriate times of the daily cycle. Rhythms of neuronal activity of the suprachiasmatic nuclei (SCN) of the hypothalamus can be inhibited and phase-shifted by application of melatonin. The firing rate of SCN neurones of rats can be inhibited by iontophoretic application of melatonin. These data are in good agreement with the high density of melatonin receptors found in the SCN of most--but not all-mammalian species. On the other hand, activity-rest cycles appear to be perfectly normal in animals which lack a daily melatonin rhythm. This, however, might be a laboratory artefact, and this system will probably fail when challenged in a complex situation.

Animals↗

PubMed1995

A short red light pulse during dark phase of LD-cycle perturbs the hamster's circadian clock.

In this study we investigated the influence of red light< which naturally occurs during dawn and dusk, on locomotor activity and body temperature rhythms of Djungarian hamsters (Phodopus sungarus). A single weak red light pulse given 2 h before regular lights on had acute as well as long-term effects persisting for several days following exposure. The hamsters immediately stopped their locomotor activity, accompanied by a drop in body temperature. In the following undisturbed nights (ID 16:8) the nocturnal activity stopped earlier than usual. This lasting effect of the light pulse was more pronounced than the acute effect. The activity phase compressed gradually during 3 to 5 days after the light pulse was administered while time of activity onset was almost unaffected. It took 6 to 11 days for complete recovery of the original activity phase. The maximal activity compression and the recovery period depended on the duration of the single red light pulse and its intensity. Red light pulses of 15 min duration were about twice effective as 1 min pulses; and the effect of a red light pulse of 130 mW/m2 was about 1.5 times stronger than a 30 mW/m2 red light pulse. The maximal value of activity phase compression reached in this experiment was 2.5 + 0.2 h with a recovery period of 11.1 +/- 0.3 days following a given red light pulse of 90 mW/m2 and 15 min. The "morning oscillator" seems to be persistently affected. This indicates a very high photosensitivity of the Djungarian hamster's circadian system to red light.

Animals↗

PubMed1995

Melatonin synthesis in the retina and pineal gland of Djungarian hamsters at different times of the year.

Daily profiles of melatonin content in the retina of Djungarian hamsters were measured throughout the course of a year. Peak levels of retinal melatonin were found at various times of the day at different seasons. In a subsequent study we determined concurrently daily profiles of nine indole metabolites (tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophol, N-acetylserotonin, melatonin, 5-methoxyindoleacetic acid and 5-methoxytryptophol) in samples of hamster retina and pineal gland at the four different seasons. Measurements were made using HPLC coupled to a coulometric electrode detection system. Large seasonal variations in the levels and daily rhythm amplitudes of the different indole metabolites were found in the pineal glands. Due to technical problems and unknown interfering substances only tryptophan and serotonin could be determined in the retinas at all four seasons. Despite this, the ability to measure levels of several metabolites in the same sample and in different tissues of the same animals permitted more accurate comparisons of the components involved in melatonin synthesis. Our data suggest that the level of retinal melatonin is regulated and controlled locally within the retina itself. However, long-term feedback mechanisms from other sources of melatonin are not excluded but are rather likely.

Animals↗

PubMed1993

Cold exposure and food restriction facilitate physiological responses to short photoperiod in Djungarian hamsters (Phodopus sungorus).

We investigated the influence of ambient temperature (Ta) and food availability on seasonal timing and extent of physiological responses to short photoperiod (SP), in particular daily torpor, in Djungarian hamsters (Phodopus sungorus). Exposure of hamsters to cold temperature (Ta = 5 degrees C), relative to warm Ta (23 degrees C), resulted in: 1) a significant advance (P < 0.05) of the first occurrence of torpor among cold-exposed hamsters (days 52-97 vs. days 83-99 in SP); 2) a higher (P < 0.01) incidence of torpor (48% vs. 20% torpid animals/day); 3) a higher (P < 0.05) degree of molt into the winter pelt; and 4) an accelerated reduction of body weights (P < 0.001). However, within SP/cold-Ta exposed groups, individual hamsters clearly showed different tendencies for torpor (torpor on 0-95% of days observed). Therefore, we evaluated the effects of small changes in Ta on torpor frequency and extension by subjecting the same SP-adapted individuals to varying temperatures. Lowering of Ta from 15 degrees C to 10 degrees C and 5 degrees C caused significant (P < 0.05) increases in the incidence of torpor (20%, 33%, and 40%, respectively) and lower minimal body temperatures during hypothermia (P < 0.05). When the same animals were subjected to 24-48 h lasting periods of food restriction (60% of the ad libitum intake), torpor frequency further increased 1.8- to 2.6-fold at all Tas. These results show that Ta and food availability are effective in modifying both seasonal timing and extent of photoperiodically controlled adaptations. This integration of multiple environmental cues, combined with a pronounced within-species variability of winter adjustments, indicates that Djungarian hamsters are capable of flexible physiological responses towards unpredictable climatic changes in the environment.

Animals↗

PubMed1991

Cold prevents the light induced inactivation of pineal N-acetyltransferase in the Djungarian hamster, Phodopus sungorus.

In the Djungarian hamster seasonal acclimatization is primarily controlled by photoperiod, but exposure to low ambient temperature amplifies the intensity and duration of short day-induced winter adaptations. The aim of this study was to test, whether the pineal gland is involved in integrating both environmental cues. Exposure of hamsters to cold (0 degrees C) reduces the sensitivity of the pineal gland to light at night and prevents inactivation of N-acetyltransferase (NAT). The parallel time course of NAT activity and plasma norepinephrine content suggests that circulating catecholamines may stimulate melatonin synthesis under cold load.

Acetyltransferases↗

PubMed1991

Role of the sympathetic innervation in the cold-induced activation of 5'-deiodinase in brown adipose tissue of the Djungarian hamster.

The importance of the sympathetic innervation in the regulation of 5'-deiodinase activity in the interscapular brown adipose tissue (BAT) of the Djungarian hamster was studied. Interscapular BAT of Djungarian hamsters was either unilaterally or bilaterally denervated, and thereafter the animals were maintained at thermoneutral temperature or exposed to 0 degree C for 24 h. Denervation reduced the norepinephrine content to 2-10% of the level in the control groups. Unilateral denervation was as effective as bilateral denervation in depressing the norepinephrine content of the interscapular BAT. Cold exposure for 24 h resulted in a pronounced 5'-deiodinase activation. Denervation reduced, but did not completely prevent, the cold-induced increase in 5'-deiodinase activity. The basal level of 5'-deiodinase activity at thermoneutral temperature was not reduced by denervation. We conclude that cold-induced activation of BAT 5'-deiodinase primarily depends on the intact sympathetic innervation.

Adipose Tissue, Brown↗

PubMed1990

Tryptophan administration inhibits nocturnal N-acetyltransferase activity and melatonin content in the rat pineal gland. Evidence that serotonin modulates melatonin production via a receptor-mediated mechanism.

In the rat pineal gland, the activity of serotonin N-acetyltransferase (NAT) and the concentration of melatonin are normally high at night; conversely, the concentration of serotonin (5-HT), the precursor of melatonin, is low. Since tryptophan administration increases the concentration of pineal 5-HT at night, we examined its effect of melatonin production. Nighttime tryptophan loading led to substantial increases in pineal 5-hydroxytryptophan, 5-hydroxyindole acetic acid (5-HIAA), and 5-HT but a highly significant reduction in NAT activity in comparison to saline-injected controls. In contrast to other measured indoles, melatonin levels also were significantly diminished by tryptophan loading. Nocturnally high pineal norepinephrine levels were unaltered by tryptophan administration. The idea that high concentrations of 5-HT could lead to substrate inhibition of NAT activity was not supported by kinetic analysis of control NAT levels versus tryptophan-inhibited NAT activity under varied substrate concentrations. Hypotheses to explain these results include the possibility that tryptophan inhibition of melatonin synthesis is mediated by the release of 5-HT from the pinealocyte and its subsequent autocrine action on melatonin production.

5-Hydroxytryptophan↗

PubMed1990

Inhibition of 5'-deiodination of thyroxine suppresses the cold-induced increase in brown adipose tissue messenger ribonucleic acid for mitochondrial uncoupling protein without influencing lipoprotein lipase activity.

Young adult male and female Djungarian hamsters were exposed to ambient temperatures of 23 or 0 C for 12 h; half of the animals in each group were treated with iopanoic acid to suppress the peripheral conversion of T4 to the thermotropically active thyroid hormone T3 by the enzyme 5'-deiodinase (5'D). Brown adipose tissue (BAT) mRNA for uncoupling protein (UCP), BAT lipoprotein lipase (LPL) activity, and 5'D activity were measured at the conclusion of the study. A temperature of 0 C produced large rises in 5'D and LPL activities and a similar large increase in UCP mRNA within the 12-h exposure period. When 5'D activity was inhibited with iopanoic acid, mRNA for UCP was reduced, while LPL activity was unaffected. The results show that the optimal production of mRNA for BAT UCP depends on the availability of T3; however, T3 is not required for the cold-induced activation of LPL activity in BAT.

Adipose Tissue, Brown↗

PubMed1989

Melatonin, serotonin, 5-hydroxyindole-3-acetic acid and N-acetyltransferase in the pineal of the European hamster (Cricetus cricetus) kept under natural environmental conditions: lack of a day/night rhythm in melatonin formation in spring and early summer.

In female European hamsters killed in spring and early summer, pineal melatonin content exhibited no day/night rhythm. Absolute levels measured were relatively low, being on the order of daytime levels detected in other hamster species. An absence of day/night changes in the activity of N-acetyltransferase was also observed. However, a marked rhythm in pineal serotonin (5-HT) was found, an abrupt large increase being observed at the beginning of the light period. The day/night rhythm of pineal 5-HIAA content is similar to that of 5-HT. This absence of rhythm in pineal melatonin formation might mean that in the European hamster it is not melatonin but another substance that is of importance in photoperiodism. An absence of melatonin rhythm, however, could also be simply a peculiar pattern of melatonin production observed at a given period of the year. In this case, melatonin would be able to transduce photoperiodic information in the European hamster, as in other photoperiodic species.

Acetyltransferases↗

PubMed1989

Photoperiod and thermoregulation in vertebrates: body temperature rhythms and thermogenic acclimation.

Evidence has recently begun to accumulate that photoperiodic responses of mammals and birds may affect the control of energy balance and thermoregulation. Exposure to short photoperiod can lower the set point for body temperature regulation in birds and mammals, as well as the voluntarily selected body temperature in ectothermic lizards. This decrease is accompanied by a reorganization of circadian or ultradian rhythms of body temperature, particularly an increase in periods spent at rest with minimum body temperatures. Short photoperiod is also used as an environmental cue for induction of seasonal torpor or facilitation of hibernation. During winter, cold tolerance of small mammals is improved by an increase of nonshivering thermogenesis in brown fat. Thermogenic capacity of brown fat (respiratory enzymes, mitochondria, uncoupling protein) is enhanced in response to short photoperiod. This response is mediated via an increase in the activity of sympathetic innervation in brown fat. Moreover, an exposure to short photoperiod prior to low temperatures may act in preparing brown fat for facilitated thermogenesis during acclimation to cold. This shows that photoperiodic control not only affects energy balance indirectly via the control of reproduction or body mass, but may directly interact with central control of thermoregulation and may influence the process of acclimatization.

Activity Cycles↗