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Dive into the research topics where Werner Wittkowski is active.

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Featured researches published by Werner Wittkowski.


Neurosignals | 1999

Melatonin in Epilepsy: First Results of Replacement Therapy and First Clinical Results

J.-D. Fauteck; H. Schmidt; Alexander Lerchl; G. Kurlemann; Werner Wittkowski

At a single evening dose of 5–10 mg, melatonin (MLT), the pineal gland hormone, can exert a positive effect on the frequency of epileptic attacks in children with sleep disturbances of various etiologies. We have shown that the sleep behavior can be normalized and an existing epilepsy can be favorably influenced. Pretherapeutic MLT secretion profiles can provide new information concerning the origin and treatment of these disturbances. In vitro experiments suggest that this effect might be the result of the interaction between MLT and MLT-specific receptors in the neocortex. Due to its favorable safety profile, MLT can be liberally administered in the specified doses and be considered as a useful antiepileptic drug.


Cell and Tissue Research | 1988

Photoperiod-dependent changes in TSH-like immunoreactivity of cells in the hypophysial pars tuberalis of the Djungarian hamster, Phodopus sungorus

Werner Wittkowski; M. Bergmann; Klaus Hoffmann; F. Pera

SummaryCertain secretory cells in the hypophysial pars tuberalis of the Djungarian hamster display marked circannual structural alterations. The present investigation deals with the immunohistochemical properties of this cell group. A distinct TSH-like immunoreactivity was found in secretory cells of this type in the pars tuberalis of animals exposed to long photoperiods, whereas under short photoperiods the TSH-like immunoreactivity was nearly absent. In the pars distalis, the number and distribution of TSH-positive cells did not differ significantly between animals maintained under long and under short photoperiods. LH-and FSH-positive cells could not be detected in the pars tuberalis, but they are clearly present in the pars distalis of both groups of hamsters. Our immunocytochemical results suggest that photoperiodic stimuli influence the secretory activity of TSH-like immunoreactive cells in the pars tuberalis. A connection with the neuroendrocrine-thyroid axis is discussed.


Brain Research | 2002

Long-term effects of St. John's wort and hypericin on monoamine levels in rat hypothalamus and hippocampus.

Veronika Butterweck; Tobias M. Böckers; Brigitte Korte; Werner Wittkowski; Hilke Winterhoff

Hypericum perforatum L. (St. Johns wort) is one of the leading psychotherapeutic phytomedicines and, because of this, great effort has been devoted to clarifying its mechanism of action. Chronic effects of St. Johns wort and hypericin, one of its major active compounds, on regional brain amine metabolism have not been reported yet. We used a high-performance liquid chromatography system to examine the effects of short-term (2 weeks) and long-term (8 weeks) administration of imipramine, Hypericum extract or hypericin on regional levels of serotonin (5-HT), norepinephrine, dopamine and their metabolites in the rat brain. We focused our interest on the hypothalamus and hippocampus, as these brain regions are thought to be involved in antidepressant drug action. Imipramine (15 mg/kg, p.o.), Hypericum extract (500 mg/kg, p.o.), and hypericin (0.2 mg/kg, p.o.) given daily for 8 weeks significantly increased 5-HT levels in the hypothalamus (P<0.05). The 5-HT turnover was significantly lowered in both brain regions after 8 weeks of daily treatment with the Hypericum extract (both P<0.05). Consistent changes in catecholamine levels were only detected in hypothalamic tissues after long-term treatment. Comparable to imipramine, Hypericum extract as well as hypericin significantly decreased 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the hypothalamus (P<0.01). Our data clearly show that long-term, but not short-term administration of St. Johns wort and its active constituent hypericin modify levels of neurotransmitters in brain regions involved in the pathophysiology of depression.


International Review of Cytology-a Survey of Cell Biology | 1998

Cell and molecular biology of the pars tuberalis of the pituitary.

Werner Wittkowski; Jürgen Bockmann; Michael R. Kreutz; Tobias M. Böckers

The pars tuberalis of the adenohypophysis is mainly composed of a special type of endocrine cells, pars tuberalis-specific cells, lining the primary capillary plexus of the hypophysial portal system. Dense expression of melatonin receptors and marked changes in morphological appearance, production pattern, and secretory activity during annual cycle show that these cells are highly sensitive to changes in photoperiod. This leads to the hypothesis that the pars tuberalis is involved in the transmission of photoperiodic stimuli to endocrine targets. Several investigations support the theory that pars tuberalis-specific cells are multipotential cells exerting a modulatory influence on the secretory activity of the pars distalis. Specifically, there is accumulating evidence that seasonal modulation of prolactin secretion, independent of hypothalamic input, is due to melatonin-regulated activity of pars tuberalis-specific cells. The exact nature of secretory products and their effects within neuroendocrine regulation, however, remain rather enigmatic. Accordingly, molecular mechanisms regulating gene expression under the influence of photoperiod, respectively, circulating melatonin levels are still incomplete. Recent cloning of melatonin receptor genes and new data on intracellular signal transduction will probably lead to new insights on melatonin action and pars tuberalis-specific cell physiology.


Cellular and Molecular Life Sciences | 2005

Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment

Paolo Zatta; Michelangelo Raso; P. Zambenedetti; Werner Wittkowski; Luigi Messori; F. Piccioli; P. L. Mauri; Mariano Beltramini

Abstract.Recent reports describe successful treatment using copper chelation therapy in neurodegenerative animal models. However, the success claimed for chelation therapy in neurodegenerative diseases is still rather controversial. To acquire new information on copper metabolism/homeostasis, we utilized cuprizone, a very sensitive and selective copper-chelating agent with well-known neurotoxic properties, as a relevant chemical model in mice. Upon cuprizone treatment, mice developed a pronounced astrocytosis, with brain oedema and spongiosis characterised by vacuolisations of the neuropil predominantly in the white matter. In addition, cuprizone treatment severely altered copper and zinc homeostasis in the central nervous system (CNS) as well as in all other tissues examined, with increasing metal ion concentrations particularly in the CNS. Concomitant with this increase in the Cu and Zn concentration in the brain, metallothionein-I and -II were also highly immunoreactive in astrocyte, consistent with the astrocytosis and demyelination observed in our and other laboratories.


Cell and Tissue Research | 1984

Influence of photoperiod on the ultrastructure of the hypophysial pars tuberalis of the Djungarian hamster, Phodopus sungorus.

Werner Wittkowski; Maria Hewing; Klaus Hoffmann; M. Bergmann; Jörg Fechner

SummaryConspicuous cytological differences are found between specific secretory cells of the hypophysial pars tuberalis of Djungarian hamsters exposed to long and short photoperiods. The cells differ with respect to the shapes of perikarya and nuclei and show diverse amounts of secretory granules, lysosome-like bodies and glycogen.


Neuroscience Letters | 1994

The adult human cerebellum is a target of the neuroendocrine system involved in the circadian timing

Jan-Dirk Fauteck; Alexander Lerchl; Markus Bergmann; Morten Møller; Franco Fraschini; Werner Wittkowski; Bojidar Stankov

In an investigation aimed at comprehensive mapping of the adult human brain with respect to receptor sites for the pineal hormone melatonin, we consistently observed specific binding in the cerebellum. Autoradiography and in vitro binding analysis with 125I-labeled melatonin were used to examine the location and the properties of these binding sites. In all cerebellar lobes, highest-density specific binding was localized to the external zone of the molecular layer. The binding was rapid, saturable, displaceable, specific and of high affinity. Physiological concentrations of NaCl decreased the affinity, while presence of calcium ions promoted it. The non-hydrolyzable GTP analog, GTP gamma S, inhibited binding in a dose-dependent manner and provoked a shift towards low affinity. The results strongly suggest that these binding sites may be functional melatonin receptors, and indicate that the adult human cerebellum is a target of melatonin, the pineal hormone involved in the control of the circadian timing.


Cell and Tissue Research | 1989

Ultrastructural localization of thyrotropin (TSH)-like immunoreactivity in specific secretory cells of the hypophyseal pars tuberalis in the Djungarian hamster, Phodopus sungorus

M. Bergmann; Werner Wittkowski; Klaus Hoffmann

SummarySpecific secretory cells in the hypophyseal pars tuberalis of Djungarian hamsters maintained under different photoperiods were investigated immunocytochemically by means of the colloidal gold technique using antibodies against rat thyrotropin (TSH). Secretory cells of animals kept under long photoperiods (LD16:8) showed positive staining of secretory granules (diameters 90–130 nm), whereas other intracellular structures were free of immunoreactivity. In animals kept under short photoperiods (LD8:16) secretory cells displayed increased numbers of secretory granules, but these organelles were devoid of immunoreactivity. In contrast, immunoreactivity of thyrotropes in the pars distalis did not differ between the two groups of animals investigated. The present results confirm earlier light-microscopical studies that in the pars tuberalis specific secretory cells show TSH-like immunoreactivity; however, they differ in their reactivity pattern from classical thyrotropes in the pars distalis.


Endocrinology | 1997

Initial Expression of the Common α-Chain in Hypophyseal Pars Tuberalis-Specific Cells in Spontaneous Recrudescent Hamsters1

T. M. Böckers; J. Bockmann; A. Salem; P. Niklowitz; A. Lerchl; M. Huppertz; Werner Wittkowski; M. R. Kreutz

When exposed to short-day conditions, hamsters and other long-day breeders undergo gonadal regression. With chronic exposure to short days, however, the animals become photorefractory and gonadal recrudescence occurs. The underlying mechanism for this insensitivity is still unknown. There is growing evidence, however, that specific cells of the pituitary pars tuberalis (PT) mediate these photoperiod/nonphotoperiod-dependent changes as a direct or indirect“ Zeitgeber” for the endocrine system. We investigated messenger RNA (mRNA)/protein formation for several hypophyseal hormones (β-TSH, β-LH, PRL, common α-chain) in the pars distalis (PD) and PT of female Djungarian hamsters in long photoperiod (LP) and after 18, 28, and 38 weeks of short photoperiod (SP). As indicated by gonadal and body weight, the hamsters displayed gonadal regression after 18 and 28 weeks of SP; after 38 weeks of SP, all animals showed recrudescence. At 18 and 28 weeks of SP, only PRL mRNA and protein levels were significantly reduced...


Cell and Tissue Research | 1990

Changes in TSH-immunoreactivity in the pars tuberalis and pars distalis of the fetal rat hypophysis following maternal administration of propylthiouracil and thyroxine

T.M. Böckers; Hildegard Sourgens; Werner Wittkowski; Andrea Jekat; Franz Pera

SummaryThe pars tuberalis (pt) of the adenohypophysis is unique in its close spatial relationship to the neurohemal contact area of the median eminence. The morphology of pt-specific secretory cells does not resemble cell types of the pars distalis (pd); the functional role of these cells within the endocrine system is still unknown. One group of young mature female Wistar rats received propylthiouracil (PTU), a second group thyroxine (T4) (10 mg/l each in drinking water) from about 3 weeks prior to the expected pregnancy and throughout the experiment. On gestation day 20, the fetuses were obtained by laparatomy. Serial sections from the rostral portion of the pt and from the pd were immunostained using the peroxidase-antiperoxidase method. TSH concentrations were determined by RIA in serum and pituitaries; T4 was measured in serum. An antiserum against rat (r) TSH revealed a moderate positive reaction of nearly all cells of the pt in the control group. In both experimental groups the pt-specific cells showed weak or no immunoreactivity. Sections of all groups were negative with anti(r)-LH,-GH,-PRL. In contrast to controls, only a few immature TSH-cells could be found in sections of the pd in the T4-group, while concentrations of TSH in blood and hypophysis were very low. TSH-cells in the PTU-group were enlarged and less intensely stained. TSH-concentrations were decreased in the hypophysis, blood levels were elevated. All sections of the pd-specific cell populations showed positive immunoreactions with anti(r)-LH,-GH,-PRL. The present results suggest that pt-specific secretory cells of the fetal rat possess TSH immunoreactivity but do not resemble the thyrotropes of the pd. Marked differences in immunoreactivity displayed by the experimental groups indicate that pt-specific cells respond to changes in the fetal thyroid status and are a component of the thyroid-regulating system in addition to the thyrotropes of the pd. This novel aspect of pt function is discussed in connection with recent results concerning melatonin receptors found in the pt and the inhibitory influence of the pineal gland exerted on the thyroid gland.

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J. Bockmann

University of Münster

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Michael R. Kreutz

Leibniz Institute for Neurobiology

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Tobias M. Böckers

Leibniz Institute for Neurobiology

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M. Bergmann

University of Münster

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