Search Results - (Author, Cooperation:T. M. Boeckers)

2012-06-16

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Adaptor Proteins, Signal Transducing/*genetics ; Animals ; Autistic Disorder/*genetics/pathology ; Behavior, Animal/*physiology ; Dendritic Spines/genetics ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/*genetics ; Psychomotor Agitation/*genetics/pathology ; Receptors, Ionotropic Glutamate/metabolism ; Synapses/metabolism ; Up-Regulation ; Vocalization, Animal/physiology

1365-2826

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Hypophyseal pars tuberalis (PT)-specific cells are known to exhibit remarkable seasonal changes in morphology especially in photoperiodic animals like the Djungarian hamster Phodopus sungorus. Their high density of melatonin-receptors leads to the supposition that fluctuations in circulating melatonin levels are a crucial factor for the morphological alterations induced by photoperiodic signals. To prove this hypothesis the nocturnal elevation of melatonin in long photoperiods was prolonged by late afternoon administration of melatonin. We investigated whether this treatment induces cytological changes usually observable under short photoperiod. Electron microscopy revealed that in contrast to hamsters maintained in long photoperiods PT-specific cells of hamsters injected with melatonin or those kept in short photoperiods appear inactive, containing a relatively high number of secretory granules, sparse endoplasmatic reticulum, irregularly outlined and invaginated cell nuclei and a high amount of glycogen. Furthermore immunoreactivity for the common α-chain of glycoprotein hormones and β-TSH was significantly weaker in hamsters kept in short photoperiods or daily injected with melatonin than untreated or vehicle injected controls in long photoperiod. These results demonstrate that an exogenous prolongation of the elevated nocturnal melatonin levels causes a similar morphological appearance of PT-specific cells as observed in short photoperiods. It is tempting to speculate that the melatonin signal is a direct ‘Zeitgeber’ for the transduction of photoperiodic information to the secretory activity in this cell type.

Electronic Resource

1460-9568

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Recently emerging evidence suggests important roles for inositol polyphosphates and inositol phospholipids in neuronal Ca2+ signalling, membrane vesicle trafficking and cytoskeletal rearrangement. A prerequisite for a detailed physiological characterization of the signalling of both potential second messengers inositol-(1,3,4,5)-tetrakisphosphate (InsP4) and phosphatidylinositol-3,4,5-trisphosphate (PtdlnsP3) in the nervous system is the precise cellular localization of their receptors. Based on the cDNA sequence of a recently cloned brain-specific receptor with high affinity for both InsP4 and PtdlnsP3 (InsP4–PtdlnsP3R), p42IP4/centaurin-α, we localized the mRNA and the protein in rat brain. In situ hybridization revealed a widespread expression of the InsP4–PtdlnsP3R with prominent labelling in cerebellum, hippocampus, cortex and thalamus, which moreover is developmentally regulated. Using peptide-specific antibodies, the immunoreactivity was localized in the adult brain in the vast majority of neuronal cell types and probably also in some glial cells. Prominent immunoreactivity was found in axonal processes and in cell types characterized by extensive neurites. In the hypothalamus a subpopulation of parvocellular neurons in the peri- and paraventricular nuclei was most heavily labelled. This was confined by strong immunoreactivity in the lamina externa of the median eminence in close proximity to portal plexus blood vessels. Electron microscopy revealed that the InsP4-PtdlnsP3R was frequently associated with presynaptic vesicular structures. Further studies should identify the role of the InsP4-PtdlnsP3R in cellular neural processes.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The ProSAP/Shank family of multidomain proteins of the postsynaptic density (PSD) can either directly or indirectly interact with NMDA-type and metabotropic glutamate receptors and the actin-based cytoskeleton. In a yeast two hybrid screen utilizing a proline-rich domain that is highly conserved among the ProSAP/Shank family members, we isolated several cDNA clones coding for the insulin receptor substrate IRSp53. The specificity of this interaction was confirmed in transfected COS cells. Co-immunoprecipitation of IRSp53 and ProSAP2 solubilized from rat brain membranes indicates that the interaction occurs in vivo. The C-terminal SH3 domain of IRSp53 is responsible for the interaction with a novel proline-rich consensus sequence of ProSAP/Shank that was characterized by mutational analysis. IRSp53 is a substrate for the insulin receptor in the brain and acts downstream of small GTPases of the Rho family. Binding of Cdc42Hs to IRSp53 induces actin filament assembly, reorganization and filopodia outgrowth in neuronal cell lines. Our data suggest that IRSp53 can be recruited to the PSD via its ProSAP/Shank interaction and may contribute to the morphological reorganization of spines and synapses after insulin receptor and/or Cdc42Hs activation.

Electronic Resource

1432-1106

Epilepsy ; Melatonin ; Low Mg2+ ; Epileptiform field potentials ; Human

Springer Online Journal Archives 1860-2000

Medicine

Abstract Scizure susceptibility waxes and wanes in an apparently circadian manner in many epileptic patients. Fluctuations of melatonin concentration with highest levels during the night and lowest levels in the early morning could be involved in this phenomenon. Therefore, the action of melatonin on epileptic activity was tested. The experiments were carried out on human temporal neocortical slices cut from tissue resected for surgical treatment of epilepsy. Autoradiographic studies were performed on parallel slices with 100–120 pmol 2-[125I]iodomelatonin/l in the absence or presence of unlabelled melatonin. High-affinity binding sites of melatonin could be demonstrated in layers II–V of the temporal cortex. The binding was saturable, specific and occurred with low capacity. In electrophysiological studies, epileptiform field potentials were elicited by omission of Mg2+ from the superfusate and recorded from layers II–V. The frequency of occurrence of epileptiform field potentials was reduced to 0.5 of the initial value with application of melatonin (10 and 100 nmol/l) in each case. This effect was reversible upon washing. The findings favour the hypothesis that melatonin depresses epileptiform neuronal activity through specific neocortical receptors.

Electronic Resource