Search results for " synapse"
showing 10 items of 44 documents
Reduction in the Motoneuron Inhibitory/Excitatory Synaptic Ratio in an Early-Symptomatic Mouse Model of Amyotrophic Lateral Sclerosis
2010
Excitotoxicity is a widely studied mechanism underlying motoneuron degeneration in amyotrophic lateral sclerosis (ALS). Synaptic alterations that produce an imbalance in the ratio of inhibitory/excitatory synapses are expected to promote or protect against motoneuron excitotoxicity. In ALS patients, motoneurons suffer a reduction in their synaptic coverage, as in the transition from the presymptomatic (2-month-old) to early-symptomatic (3-month-old) stage of the hSOD1(G93A) mouse model of familial ALS. Net synapse loss resulted from inhibitory bouton loss and excitatory synapse gain. Furthermore, in 3-month-old transgenic mice, remaining inhibitory but not excitatory boutons attached to mot…
Cytoskeletal stabilization of inhibitory interactions in immunologic synapses of mature human dendritic cells with natural killer cells
2011
Abstract Human mature dendritic cells (DCs) can efficiently stimulate natural killer (NK)–cell responses without being targeted by their cytotoxicity. To understand this important regulatory crosstalk, we characterized the development of the immunologic synapse between mature DCs and resting NK cells. Conjugates between these 2 innate leukocyte populations formed rapidly, persisted for prolonged time periods and matured with DC-derived f-actin polymerization at the synapse. Polarization of IL-12 and IL-12R to the synapse coincided with f-actin polymerization, while other activating and inhibitory molecules were enriched at the interface between DCs and NK cells earlier. Functional assays re…
Endothelial Nitric Oxide Synthase Regulates T Cell Receptor Signaling at the Immunological Synapse
2006
The role of nitric oxide (NO) in T cells remains controversial, and the origin and localization of endogenous NO and whether it regulates lymphocyte activation are unclear. We show here that, within minutes of binding to antigen, T cells produce NO via endothelial nitric oxide synthase (eNOS). This process required increased intracellular Ca2+ and phosphoinositide3-kinase activity. By using an eNOS-green fluorescent fusion protein and fluorescent probes to detect NO, we show that eNOS translocates with the Golgi apparatus to the immune synapse of T helper cells engaged with antigen-presenting cells (APC), where it was fully activated. Overexpression of eNOS prevented the central coalescence…
eNOS S-nitrosylates β-actin on Cys374 and regulates PKC-θ at the immune synapse by impairing actin binding to profilin-1.
2017
The actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C-¿ (PKC-¿) at the central supramolecular activation cluster (c-SMAC) of the IS. eNOS translocated with the Golgi to the IS and partially colocalized with F-actin around the c-SMAC. This resulted in reduced actin polymerization and centripetal retrograde flow of ß-actin and PKC-¿ from the lamellipodium-like distal (d)-SMAC, promoting PKC-¿ activation. Furthermore, eNOS-derived NO S-nitrosylated ß-…
Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants
2020
Mice lacking GAD1 show neonatal mortality, but the human phenotype associated with GAD1 disruption is poorly characterized. Neuray et al. describe six patients with biallelic GAD1 mutations, presenting with early-infantile onset epilepsy, neurodevelopmental delay, muscle weakness and non-CNS manifestations.
Effects of Presynaptic Mutations on a Postsynaptic Cacna1s Calcium Channel Colocalized with mGluR6 at Mouse Photoreceptor Ribbon Synapses
2008
Purpose Photoreceptor ribbon synapses translate light-dependent changes of membrane potential into graded transmitter release via L-type voltage-dependent calcium channel (VDCC) activity. Functional abnormalities (e.g., a reduced electroretinogram b-wave), arising from mutations of presynaptic proteins, such as Bassoon and the VDCCalpha1 subunit Cacna1f, have been shown to altered transmitter release. L-type VDCCalpha1 subtype expression in wild-type and mutant mice was examined, to investigate the underlying pathologic mechanism. Methods Two antisera against Cacna1f, and a Cacna1f mouse mutant (Cacna1fDeltaEx14-17) were generated. Immunocytochemistry for L-type VDCCalpha1 subunits and addi…
Ribbon synapses of the mammalian retina contain two types of synaptic bodies--ribbons and spheres.
1989
The present paper reports that the synaptic bodies of the retinal ribbon synapses in rat, guinea pig, golden hamster and mouse are a heterogeneous population of organelles. In addition to the well-known synaptic ribbons sensu stricto which consist of a platelike electron-dense central structure surrounded by electron-lucent synaptic vesicles, there are what is termed synaptic spheres, in which the core is not platelike, but round to oval. In rat retinae procured at day, ribbons outnumbered spheres by a factor of 4. At night spheres were not seen in photoreceptor cells. Spheres, like ribbons, may lie some distance from the synaptic site, perhaps indicating transit from their site of origin t…
Synaptic vesicle alterations in rod photoreceptors of synaptophysin-deficient mice.
2001
Abstract The abundance of the integral membrane protein synaptophysin in synaptic vesicles and its multiple possible functional contributions to transmitter exocytosis and synaptic vesicle formation stand in sharp contrast to the observed lack of defects in synaptophysin knockout mice. Assuming that deficiencies are compensated by the often coexpressed synaptophysin isoform synaptoporin, we now show that retinal rod photoreceptors, which do not synthesize synaptoporin either in wild-type or in knockout mice, are affected by the loss of synaptophysin. Multiple pale-appearing photoreceptors, as seen by electron microscopy, possess reduced cytoplasmic electron density, swollen mitochondria, an…
The atypical dopamine transport inhibitor, JHW 007, prevents amphetamine-induced sensitization and synaptic reorganization within the nucleus accumbe…
2013
Benztropine (BZT) analogs, a family of agents with high affinity for the dopamine transporter have been postulated as potential treatments in stimulant abuse due to their ability to attenuate a wide range of effects evoked by psychomotor stimulants such as cocaine and amphetamine (AMPH). Repeating administration of drugs, including stimulants, can result in behavioral sensitization, a progressive increase in their psychomotor activating effects. We examined in mice the sensitizing effects and the neuroplasticity changes elicited by chronic AMPH exposure, and the modulation of these effects by the BZT derivative and atypical dopamine uptake inhibitor, JHW007, a candidate medication for stimu…
Mouse photoreceptor synaptic ribbons lose and regain material in response to illumination changes
2004
Abstract Chemical synapses equipped with ribbons are tonically active, high-output synapses. The ribbons may play a role in the trafficking of synaptic vesicles. Recent findings in retinal rod cells of BALB/c mice indicate that ribbons are large and smooth in the dark phase, and, due to the formation and release of protrusions, small during the light phase. As a consequence of these changes, ribbons may traffick fewer vesicles in the light than in the dark phases. The aim of the present study was to find out whether the above ribbon changes in this mouse strain are strictly illumination-dependent and which signalling processes may be involved. Here, we show that ribbons form protrusions and…