655 research outputs found
Minireview: recent progress in gonadotropin-releasing hormone neuronal migration
Neurons that synthesize GnRH are critical brain regulators of the reproductive axis, yet they originate outside the brain and must migrate over long distances and varied environments to get to their appropriate positions during development. Many studies, past and present, are providing clues for the types of molecules encountered and movements expected along the migratory route. Recent studies provide real-time views of the behavior of GnRH neurons in the context of in vitro preparations that model those in vivo. Live images provide direct evidence of the changing behavior of GnRH neurons in their different environments, showing that GnRH neurons move with greater frequency and with more alterations in direction after they enter the brain. The heterogeneity of molecular phenotypes for GnRH neurons likely ensures that multiple external factors will be found that regulate the migration of different portions of the GnRH neuronal population at different steps along the route. Molecules distributed in gradients both in the peripheral olfactory system and basal forebrain may be particularly influential in directing the appropriate movement of GnRH neurons along their arduous migration. Molecules that mediate the adhesion of GnRH neurons to changing surfaces may also play critical roles. It is likely that the multiple external factors converge on selective signal transduction pathways to engage the mechanical mechanisms needed to modulate GnRH neuronal movement and ultimately migration
Influence of Organic Solvents on Secondary Brain Damage after Experimental Traumatic Brain Injury
Many compounds tested for a possible neuroprotective effect after traumatic brain injury (TBI) are not readily soluble and therefore organic solvents need to be used as a vehicle. It is, however, unclear whether these organic solvents have intrinsic pharmacological effects on secondary brain damage and may therefore interfere with experimental results. Thus, the aim of the current study was to evaluate the effect of four widely used organic solvents, dimethylsulfoxide (DMSO), Miglyol 812 (Miglyol(R)), polyethyleneglycol 40 (PEG 40), and N-2-methyl-pyrrolidone (NMP) on outcome after TBI in mice. A total of 143 male C57Bl/6 mice were subjected to controlled cortical impact (CCI). Contusion volume, brain edema formation, and neurological function were assessed 24 h after TBI. Test substances or saline were injected intraperitoneally (i.p.) 10 min before CCI. DMSO, Miglyol, and PEG 40 had no effect on post-traumatic contusion volume after CCI;NMP, however, significantly reduced contusion volume and brain edema formation at different concentrations. The use of DMSO, Miglyol, and PEG 40 is unproblematic for studies investigating neuroprotective treatment strategies as they do not influence post-traumatic brain damage. NMP seems to have an intrinsic neuroprotective effect that should be considered when using this agent in pharmacological experiments;further, a putative therapeutic effect of NMP needs to be elucidated in future studies
Glycolipids of the mouse peritoneal macrophage. Alterations in amount and surface exposure of specific glycolipid species occur in response to inflammation and tumoricidal activation
We have characterized the major glycolipid constituents of the mouse peritoneal macrophage, and have demonstrated that alterations in the amount and in the accessibility of specific glycolipid species to galactose oxidase/NaB3H4 labeling, an indicator of glycolipid surface exposure, occur in response to inflammation and as a consequence of activation to a tumoricidal state. The key findings are: (a) Asialo GM1, a major neutral glycolipid constituent of all macrophage populations examined, is accessible to galactose oxidase/NaB3H4 labeling on the surface of TG-elicited and BCG-activated macrophages but not on resident macrophages; (b) GM1 is the predominant ganglioside constituent of the mouse macrophage. Resident macrophages contain two distinct GM1 species, as determined by cholera toxin binding, while TG-elicited and BCG-activated macrophages contain an additional GM1 species. Differences in the relative amounts of these GM1 species, as well as in their accessibility to galactose oxidase/NaB3H4 labeling, exist among the macrophage populations. These observations suggest that both a chemical and spatial reorganization of surface glycolipids occurs in response to inflammation and tumoricidal activation
{beta}3GnT2 Maintains Adenylyl Cyclase-3 Signaling and Axon Guidance Molecule Expression in the Olfactory Epithelium
In the olfactory epithelium (OE), odorant receptor stimulation generates cAMP signals that function in both odor detection and the regulation of axon guidance molecule expression. The enzyme that synthesizes cAMP, adenylyl cyclase 3 (AC3), is coexpressed in olfactory sensory neurons (OSNs) with poly-N-acetyllactosamine (PLN) oligosaccharides determined by the glycosyltransferase beta3GnT2. The loss of either enzyme results in similar defects in olfactory bulb (OB) innervation and OSN survival, suggesting that glycosylation may be important for AC3 function. We show here that AC3 is extensively modified with N-linked PLN, which is essential for AC3 activity and localization. On Western blots, AC3 from the wild-type OE migrates diffusely as a heavily glycosylated 200 kDa band that interacts with the PLN-binding lectin LEA. AC3 from the beta3GnT2(-/-) OE loses these PLN modifications, migrating instead as a 140 kDa glycoprotein. Furthermore, basal and forskolin-stimulated cAMP production is reduced 80-90% in the beta3GnT2(-/-) OE. Although AC3 traffics normally to null OSN cilia, it is absent from axon projections that aberrantly target the OB. The cAMP-dependent guidance receptor neuropilin-1 is also lost from beta3GnT2(-/-) OSNs and axons, while semaphorin-3A ligand expression is upregulated. In addition, kirrel2, a mosaically expressed adhesion molecule that functions in axon sorting, is absent from beta3GnT2(-/-) OB projections. These results demonstrate that PLN glycans are essential in OSNs for proper AC3 localization and function. We propose that the loss of cAMP-dependent guidance cues is also a critical factor in the severe axon guidance defects observed in beta3GnT2(-/-) mice
Quantitative analysis of neutral glycosphingolipids from human lymphocyte subpopulations
Stromal cell-derived factor-1 (chemokine C-X-C motif ligand 12) and chemokine C-X-C motif receptor 4 are required for migration of gonadotropin-releasing hormone neurons to the forebrain
Gonadotropin-releasing hormone (GnRH) neurons migrate from the vomeronasal organ (VNO) in the nasal compartment to the basal forebrain in mice, beginning on embryonic day 11 (E11). These neurons use vomeronasal axons as guides to migrate through the nasal mesenchyme. Most GnRH neurons then migrate along the caudal branch of the vomeronasal nerve to reach the hypothalamus. We show here that stromal cell-derived factor-1 [SDF-1, also known as chemokine C-X-C motif ligand 12 (CXCL12)] is expressed in the embryonic nasal mesenchyme from as early as E10 in an increasing rostral to caudal gradient that is most intense at the border of the nasal mesenchyme and the telencephalon. Chemokine C-X-C motif receptor 4 (CXCR4), the receptor for SDF-1, is expressed by neurons in the olfactory epithelium and VNO. Cells derived from these sensory epithelia, including migrating GnRH neurons and ensheathing glial precursors of the migrating mass (MM), also express CXCR4, suggesting that they may use SDF-1 as a chemokine. In support of this, most GnRH neurons of CXCR4-/- mice fail to exit the VNO at E13, and comparatively few GnRH neurons reach the forebrain. There is also a significant decrease in the total number of GnRH neurons in CXCR4-/- mice and an increase in cell death within the VNO relative to controls. The MM is smaller in CXCR4-/- mice, suggesting that some MM cells also require SDF-1/CXCR4 function for migration and survival
Compartmentation in mammalian cerebellum: Zebrin II and P-path antibodies define three classes of sagittally organized bands of Purkinje cells.
Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance
<p>Abstract</p> <p>Background</p> <p>The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a small number of targets in the olfactory bulb such that each glomerulus is made up of axon terminals expressing just one odorant receptor. It is thought that this precision in axon targeting is required to maintain highly refined odor discrimination. We previously showed that β3GnT2<sup>−/−</sup> mice have severe developmental and axon guidance defects. The phenotype of these mice is similar to adenylyl cyclase 3 (AC3) knockout mice largely due to the significant down-regulation of AC3 activity in β3GnT2<sup>−/−</sup> neurons.</p> <p>Results</p> <p>Microarray analysis reveals that nearly one quarter of all odorant receptor genes are down regulated in β3GnT2<sup>−/−</sup> mice compared to controls. Analysis of OR expression by quantitative PCR and <it>in situ</it> hybridization demonstrates that the number of neurons expressing some odorant receptors, such as mOR256-17, is increased by nearly 60% whereas for others such as mOR28 the number of neurons is decreased by more than 75% in β3GnT2<sup>−/−</sup> olfactory epithelia. Analysis of axon trajectories confirms that many axons track to inappropriate targets in β3GnT2<sup>−/−</sup> mice, and some glomeruli are populated by axons expressing more than one odorant receptor. Results show that mutant mice perform nearly as well as control mice in an odor discrimination task. In addition, <it>in situ</it> hybridization studies indicate that the expression of several activity dependent genes is unaffected in β3GnT2<sup>−/−</sup> olfactory neurons.</p> <p>Conclusions</p> <p>Results presented here show that many odorant receptors are under-expressed in β3GnT2<sup>−/−</sup> mice and further demonstrate that additional axon subsets grow into inappropriate targets or minimally innervate glomeruli in the olfactory bulb. Odor evoked gene expression is unchanged and β3GnT2<sup>−/−</sup> mice exhibit a relatively small deficit in their ability to discriminate divergent odors. Results suggest that despite the fact that β3GnT2<sup>−/−</sup> mice have decreased AC3 activity, decreased expression of many ORs, and display many axon growth and guidance errors, odor-evoked activity in cilia of mutant olfactory neurons remains largely intact.</p
- …