Biomedical subjects

Jean-Pierre Hornung

Publications and source records attributed to Jean-Pierre Hornung.

8 recordsLinked to original sources

PubMed2006

Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice.

Serotonin [5-hydroxytryptamine (5-HT)] neurotransmission in the central nervous system modulates depression and anxiety-related behaviors in humans and rodents, but the responsible downstream receptors remain poorly understood. We demonstrate that global disruption of 5-HT2A receptor (5HT2AR) signaling in mice reduces inhibition in conflict anxiety paradigms without affecting fear-conditioned and depression-related behaviors. Selective restoration of 5HT2AR signaling to the cortex normalized conflict anxiety behaviors. These findings indicate a specific role for cortical 5HT2AR function in the modulation of conflict anxiety, consistent with models of cortical, "top-down" influences on risk assessment.

Animals↗

PubMed2006

Glutathione deficit during development induces anomalies in the rat anterior cingulate GABAergic neurons: Relevance to schizophrenia.

A series of studies in schizophrenic patients report a decrease of glutathione (GSH) in prefrontal cortex (PFC) and cerebrospinal fluid, a decrease in mRNA levels for two GSH synthesizing enzymes and a deficit in parvalbumin (PV) expression in a subclass of GABA neurons in PFC. GSH is an important redox regulator, and its deficit could be responsible for cortical anomalies, particularly in regions rich in dopamine innervation. We tested in an animal model if redox imbalance (GSH deficit and excess extracellular dopamine) during postnatal development would affect PV-expressing neurons. Three populations of interneurons immunolabeled for calcium-binding proteins were analyzed quantitatively in 16-day-old rat brain sections. Treated rats showed specific reduction in parvalbumin immunoreactivity in the anterior cingulate cortex, but not for calbindin and calretinin. These results provide experimental evidence for the critical role of redox regulation in cortical development and validate this animal model used in schizophrenia research.

Animals↗

PubMed2004

Selective neurofilament (SMI-32, FNP-7 and N200) expression in subpopulations of layer V pyramidal neurons in vivo and in vitro.

There are two main types of layer V pyramidal neurons in rat cortex. Type I neurons have tufted apical dendrites extending into layer I, produce bursts of action potentials and project to subcortical targets (spinal cord, superior colliculus and pontine nuclei). Type II neurons have apical dendrites, which arborize in layers II-IV, do not produce bursts of action potentials and project to ipsilateral and contralateral cortex. The specific expression of different genes and proteins in these two distinct layer V neurons is unknown. To distinguish between distinct subpopulations, fluorescent microspheres were injected into subcortical targets (labeling type I neurons) or primary somatosensory cortex (labeling type II neurons) of adult rats. After transport, cortical sections were processed for immunohistochemistry using various antibodies. This study demonstrated that antigens recognized by SMI-32, N200 and FNP-7 antibodies were only expressed in subcortical (type I)--but not in contralateral (type II)--projecting neurons. NR1, NR2a/b, PLCbeta1, BDNF, NGF and TrkB antigens were highly expressed in all neuronal subpopulations examined. Organotypic culture experiments demonstrated that the development of neurofilament expression and laminar specificity does not depend on the presence of the subcortical targets. This study suggests specific markers for the subcortical projecting layer V neuron subpopulations.

Animals↗

PubMed2003

Early fetal expression of GABA(B1) and GABA(B2) receptor mRNAs on the development of the rat central nervous system.

GABA(B) receptors are G-protein-coupled receptors that mediate slow onset and prolonged effects of GABA in the central nervous system (CNS). While they appear to influence developmental events, depending on where they are found at a synapse, little, if anything, is known as to the expression of GABA(B1) and GABA(B2) receptor mRNAs during the early developmental stages. We used in situ hybridization and RNase protection assays (RPA) to investigate the early fetal expression of GABA(B1) and GABA(B2) receptor mRNAs on the development of the rat CNS. Our in situ studies defined a pattern of early and strong GABA(B1) receptor mRNA expression in the spinal cord, medullar and cerebral cortex neuroepithelium of discrete brain regions on gestational day (GD) 11.5. On GD 12.5, GABA(B1) receptor mRNAs were found in the hippocampal formation, cerebral cortex, intermediate and posterior neuroepithelium, and the pontine neuroepithelium of whole brain. RPA results showed GABA(B1) receptor mRNA was intensely expressed on GD 11.5 and GD 12.5, when it was first detected in the ganglia, thalamus, and cerebellum. However, GABA(B2) receptor mRNA was not detected on GD 10.5, 11.5, or 12.5. We suggest that GABA(B1) receptor might have a role in the early fetal brain and spinal cord during pre- and post-synaptogenesis, neuronal maturation, proliferation, and migration, and may be more important than the GABA(B2) receptor in the early development of the rat CNS.

Animals↗

PubMed2003

The human raphe nuclei and the serotonergic system.

The raphe nuclei are distributed near the midline of the brainstem along its entire rostro-caudal extension. The serotonergic neurons are their main neuronal components, although a proportion of them lie in subdivisions of the lateral reticular formation. They develop from mesopontine and medullary primordia, and the resulting grouping into rostral and caudal clusters is maintained into adulthood, and is reflected in the connectivity. Thus, the mesencephalon and rostral pons, neurons within the rostral raphe complex (caudal linear, dorsal raphe, and median raphe nuclei) project primarily to the forebrain. By contrast, in the caudal pons and medulla oblongata, neurons within the caudal raphe complex (raphe magnus, raphe obscurus, raphe pallidus nuclei and parts of the adjacent lateral reticular formation) project to the brainstem nuclei and to the spinal cord. The median raphe and dorsal raphe nuclei provide parallel and overlapping projections to many forebrain structures with axon fibers exhibiting distinct structural and functional characteristics. The caudal group of the serotonergic system projects to the brainstem, and, by three parallel projections, to the dorsal, intermediate and ventral columns in the spinal cord. The serotonergic axons arborize over large areas comprising functionally diverse targets. Some projections form classical chemical synapses while many do not, thus contributing to the so-called paracrine or volume transmission. The serotonergic projections participate in the regulation of different functional (motor, somatosensory, limbic) systems; and have been associated with a wide range of neuropsychiatric and neurological disorders. Finally, recent experimental data support the role of serotonin in modulating brain development, such that a dysfunction in serotonergic transmission during early life could lead to long lasting structural and functional alterations.

Animals↗

PubMed2003

N-methyl-d-aspartate-triggered neuronal death in organotypic hippocampal cultures is endocytic, autophagic and mediated by the c-Jun N-terminal kinase pathway.

Acute excitotoxic neuronal death was studied in rat organotypic hippocampal slices exposed to 100 micro mN-methyl-d-aspartate. Fulgurant death of pyramidal neurons occurred in the CA1 and CA3 regions and was already detectable within 2 h of the N-methyl-d-aspartate administration. Morphologically, the neuronal death was neither apoptotic nor necrotic but had the hallmarks of autophagic neuronal death, as shown by acid phosphatase histochemistry in both CA1 and CA3 and by electron microscopy in CA1. The dying neurons also manifested strong endocytosis of horseradish peroxidase or microperoxidase, occurring probably by a fluid phase mechanism, and followed, surprisingly, by nuclear entry. In addition to these autophagic and endocytic characteristics, there were indications that the c-Jun N-terminal kinase pathway was activated. Its target c-Jun was selectively phosphorylated in CA1, CA3 and the dentate gyrus and c-Fos, the transcription of which is under the positive control of c-Jun N-terminal kinase target Elk1, was selectively up-regulated in CA1 and CA3. All these effects, the neuronal death itself and the associated autophagy and endocytosis, were totally prevented by a cell-permeable inhibitor of the interaction between c-Jun N-terminal kinase and certain of its targets. These results show that pyramidal neurons undergoing excitotoxic death in this situation are autophagic and endocytic and that both the cell death and the associated autophagy and endocytosis are under the control of the c-Jun N-terminal kinase pathway.

Animals↗

PubMed2002

Developmental and spatial expression pattern of syntaxin 13 in the mouse central nervous system.

Vesicular transport involves SNARE (soluble- N-ethylmaleimide-sensitive-factor-attachment-protein-receptor) proteins on transport vesicles and on target membranes. Syntaxin 13 is a SNARE enriched in brain, associated with recycling endosomes; its overexpression in PC12 cells promotes neurite outgrowth. This suggests an important role for receptor recycling during neuronal differentiation. Here we describe the spatiotemporal pattern of syntaxin 13 expression during mouse brain development. During early embryogenesis (E12-E15), it was found in the forebrain ventricular zone and in primary motor and sensory neurons in the brainstem, spinal cord and sensory ganglia. In the forebrain at E15, syntaxin 13 was not detected in neuroblasts in the intermediate zone of the embryonic hemispheric wall, while there was labeling in cortical neurons in deeper layers starting at E15-18, and progressively in later-generated neurons up to layer II around P6. Syntaxin 13 reached maximal expression in all brain divisions at about P7, followed by a decrease, with heterogeneous neuron populations displaying various staining intensities in adult brain. While usually restricted to the soma of neurons, we transiently detected syntaxin 13 in dendrites of pyramidal neurons during the first postnatal week. In conclusion, the developmentally regulated syntaxin 13 expression in various neuronal populations is consistent with its involvement in endocytic trafficking and neurite outgrowth.

Aging↗

PubMed2002

Distribution of postsynaptic GABA(A) receptor aggregates in the deep cerebellar nuclei of normal and mutant mice.

In the central nervous system, the aggregation of receptors is crucial for synapse formation and function. To study the role of presynaptic terminals in the maintenance of postsynaptic specializations, we analyzed the synaptic contacts between Purkinje cells and neurons of the deep cerebellar nuclei in two in vivo models: the Lurcher and Purkinje cell-deficient (PCD) mutant mice. These mutants lose their Purkinje cells at different postnatal stages. By using confocal scanner microscopy and immunohistochemistry, we studied the distribution of the alpha subunit of the gamma-aminobutyric acid (GABA)(A) receptor (GABA(A)Ralpha1) and gephyrin, one of its anchoring proteins, in relation to the distribution of presynaptic markers, glutamic acid decarboxylase (GAD), or synaptophysin. In Lurcher the distribution of GABA(A) receptor aggregates on the membrane of postsynaptic neurons was not affected by the important loss of GAD-positive terminals, whereas in PCD, the number of large GABA(A) receptor aggregates increased. In both mutants the number of aggregates of gephyrin decreased. Most of these remaining aggregates were clustered to form groups, some of which were in front of GAD-positive terminals. This study shows, for the first time, the localization of GABA(A)R alpha 1 in Lurcher and PCD mutant mice. It clearly establishes that GABA(A)R alpha 1 and gephyrin are differentially affected by deafferentation. Because the receptor aggregates are maintained while the gephyrin aggregates are lost, as a result some receptor aggregates are not associated with any gephyrin. These two postsynaptic components appeared to be regulated by different mechanisms.

Aging↗