Biomedical subjects

K Obst-Pernberg

Publications and source records attributed to K Obst-Pernberg.

5 recordsLinked to original sources

PubMed2001

Granule cell raphes in the developing mouse cerebellum.

The cerebellar cortex of many vertebrates shows a striking parasagittal compartmentation that is thought to play a role in the establishment and maintenance of functional cerebellar connectivity. Here, we demonstrate the existence of multiple parasagittal raphes of cells in the molecular layer of the developing cerebellar cortex of postnatal mouse. The histological appearance and immunostaining profile of the raphe cells suggest that they are migrating granule cells. We therefore conclude that the granule cell raphes previously described in birds also exist in a mammalian species. The raphes in mouse are visible on nuclear stains from around birth to postnatal day 6 and are frequently found at the boundaries of Purkinje cell segments that differentially express cadherins ("early-onset" parasagittal banding pattern). A similar relation between the raphe pattern and various markers for the early-onset banding pattern has been found in the chicken cerebellum. One of the cadherins mapped in the present study (OL-protocadherin) continues to be expressed in specific Purkinje cell segments until at least postnatal day 14. At this stage of development, the borders of the OL-protocadherin-positive Purkinje cell segments coincide with the borders of Purkinje cell segments that express zebrin II, a marker for the "late-onset" parasagittal banding pattern which persists in the adult cerebellum. These findings demonstrate that the early-onset banding pattern, as reflected in the complementary arrangement of raphes/Purkinje cell segments, and the late-onset pattern of zebrin II expression share at least some positional cues during development.

Animals↗

PubMed2001

Expression of R-cadherin and N-cadherin by cell groups and fiber tracts in the developing mouse forebrain: relation to the formation of functional circuits.

The expression of R-cadherin and N-cadherin was mapped in the postnatal forebrain of the mouse by immunohistochemistry and in situ hybridization. Results show that the two molecules are expressed in specific and restricted patterns in numerous brain nuclei, gray matter areas and cortical layers that are widely distributed throughout the mouse forebrain at postnatal day 1. The expression pattern of R-cadherin is clearly distinct from that of N-cadherin, but overlap is observed in many areas. In many cortical areas, the two cadherins have a laminar-specific distribution that varies from region to region. In addition, immunohistochemical data revealed expression of R-cadherin protein and N-cadherin protein in the neuropil of many brain regions as well as in the axons that travel in fiber tracts such as the olfactory tract, the anterior commissure, the corpus callosum, the stria terminalis and the fornix. Often, subsets of axons within the same fiber tract differentially express R-cadherin and N-cadherin, with partial overlap of expression. The targets of the cadherin-immunoreactive fiber bundles often contain neuropil as well as cell bodies of neurons that also express the same type(s) of cadherin, suggesting that R-cadherin and N-cadherin may be involved in target recognition and the establishment of connections. Specifically, the expression of R-cadherin and N-cadherin is related to the maturation of thalamocortical sensory pathways, corticofugal pathways, and pathways associated with the hippocampal complex, the piriform cortex, and the amygdala. It is also related to the development of the cell groups associated with these pathways.Together, the results from the present study indicate the possibility that the selective adhesion of neural structures that express the same type(s) of cadherin contributes to the formation of gray matter areas, neural circuits and functional connections in the postnatal forebrain of the mouse.

Aging↗

PubMed2000

Transgenic activation of Ras in neurons promotes hypertrophy and protects from lesion-induced degeneration.

Ras is a universal eukaryotic intracellular protein integrating extracellular signals from multiple receptor types. To investigate its role in the adult central nervous system, constitutively activated V12-Ha-Ras was expressed selectively in neurons of transgenic mice via a synapsin promoter. Ras-transgene protein expression increased postnatally, reaching a four- to fivefold elevation at day 40 and persisting at this level, thereafter. Neuronal Ras was constitutively active and a corresponding activating phosphorylation of mitogen-activated kinase was observed, but there were no changes in the activity of phosphoinositide 3-kinase, the phosphorylation of its target kinase Akt/PKB, or expression of the anti-apoptotic proteins Bcl-2 or Bcl-X(L). Neuronal Ras activation did not alter the total number of neurons, but induced cell soma hypertrophy, which resulted in a 14.5% increase of total brain volume. Choline acetyltransferase and tyrosine hydroxylase activities were increased, as well as neuropeptide Y expression. Degeneration of motorneurons was completely prevented after facial nerve lesion in Ras-transgenic mice. Furthermore, neurotoxin-induced degeneration of dopaminergic substantia nigra neurons and their striatal projections was greatly attenuated. Thus, the Ras signaling pathway mimics neurotrophic effects and triggers neuroprotective mechanisms in adult mice. Neuronal Ras activation might become a tool to stabilize donor neurons for neural transplantation and to protect neuronal populations in neurodegenerative diseases.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2000

Specification of neuropeptide Y phenotype in visual cortical neurons by leukemia inhibitory factor.

Building the complex mammalian neocortex requires appropriate numbers of neurochemically specified neurons. It is not clear how the highly diverse cortical interneurons acquire their distinctive phenotypes. The lack of genetic determination implicates environmental factors in this selection and specification process. We analysed, in organotypic visual cortex cultures, the specification of neurons expressing neuropeptide Y (NPY), a potent anticonvulsant. Endogenous brain-derived neurotrophic factor and neurotrophin 4/5 play no role in early NPY phenotype specification. Rather, the decision to express NPY is made during a period of molecular plasticity during which differentiating neurons with the potential to express NPY compete for the cytokine leukemia inhibitory factor which is produced in the cortex, but is negatively regulated by thalamic afferences. The neurons that fail in this competition are parvalbuminergic basket and chandelier neurons, which express NPY transiently, but will not acquire a permanent NPY expression. They switch into a facultative NPY expression mode, and remain responsive to the neurotrophins which modulate NPY expression later in development.

Animals↗

PubMed1999

Cadherins and synaptic specificity.

Cadherins are a family of cell-cell adhesion molecules that regulate morphogenesis in a variety of organs during development. In this review, we summarize recent evidence that cadherins may be involved in synaptogenesis in the vertebrate central nervous system. The first cadherin identified in synapses was N-cadherin, which is a major glycoprotein in postsynaptic density preparations. Electron microscopic studies have shown that this molecule is present at the synaptic cleft, bordering the transmitter release zone. To date, several other cadherins have also been found in synaptic junctions. Some cadherins have been observed in distinct subsets of synapses. The homophilic binding properties of cadherins may provide a molecular basis for the adhesive interactions between opposing synaptic membranes, and cadherins may promote a stable locking-in of pre- and postsynaptic membranes. Thus, cadherins may play a role in the formation and maintenance of synapses. Cadherin expression in synapses has been studied during development, regeneration, and activity-dependent plasticity. Moreover, it has been shown that each cadherin is expressed in specific neural circuits. In this context, we discuss the possibility that the differential expression of cadherins in the nervous system provides an adhesive framework for synaptic specificity.

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