0000000000148072
AUTHOR
Isabella Spiwoks-becker
showing 12 related works from this author
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…
Evidence for synergistic and complementary roles of Bassoon and darkness in organizing the ribbon synapse
2012
Abstract Ribbon synapses are tonically active high-throughput synapses. The performance of the ribbon synapse is accomplished by a specialization of the cytomatrix at the active zone (CAZ) referred to as the synaptic ribbon (SR). Progress in our understanding of the structure–function relationship at the ribbon synapse has come from observations that, in photoreceptors lacking a full-size scaffolding protein Bassoon ( Bsn Δ Ex 4 / 5 ), dissociation of SRs coincides with perturbed signal transfer. The aim of the present study has been to elaborate the role of Bassoon as a structural organizer of the ribbon synapse and to differentiate it with regard to the ambient lighting conditions. The ul…
An improved anatomical MRI technique with suppression of fixative fluid artifacts for the investigation of human postmortem brain phantoms
2016
PURPOSE Phantoms are often used to assess MR system stability in multicenter studies. Postmortem brain phantoms best replicate human brain anatomy, allowing for a combined assessment of the MR system and software chain for data analysis. However, a wash-out of fixative fluid affecting T1 values and thus T1-weighted sequences such as magnetization-prepared 180 degrees radiofrequency pulses and rapid gradient-echo (MP-RAGE) has been reported for brain phantoms, hampering their immediate use. The purpose of this study was the creation of anatomical data that provide the characteristics of conventional data while avoiding this artifact. THEORY AND METHODS Two brain phantoms were scanned at seve…
Transcriptome comparison of murine wild-type and synaptophysin-deficient retina reveals complete identity
2005
Loss of synaptophysin, one of the major synaptic vesicle membrane proteins, is surprisingly well tolerated in knockout mice. To test whether compensatory gene transcription accounts for the apparent lack of functional deficiencies, comparative transcriptome analyses were carried out. The retina was selected as the most suitable tissue since morphological alterations were observed in mutant photoreceptors, most notably a reduction of synaptic vesicles and concomitant increase in clathrin-coated vesicles. Labeled cRNA was prepared in triplicate from retinae of age- and sex-matched wild-type and mutant litter mates and hybridized to high-density microarray chips. Only three differentially expr…
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…
A human post-mortem brain model for the standardization of multi-centre MRI studies
2015
Multi-centre MRI studies of the brain are essential for enrolling large and diverse patient cohorts, as required for the investigation of heterogeneous neurological and psychiatric diseases. However, the multi-site comparison of standard MRI data sets that are weighted with respect to tissue parameters such as the relaxation times (T1, T2) and proton density (PD) may be problematic, as signal intensities and image contrasts depend on site-specific details such as the sequences used, imaging parameters, and sensitivity profiles of the radiofrequency (RF) coils. Water or gel phantoms are frequently used for long-term and/or inter-site quality assessment. However, these phantoms hardly mimic t…
Unique clockwork in photoreceptor of rat
2010
In mammals, the retina contains a clock system that oscillates independently of the master clock in the suprachiasmatic nucleus and allows the retina to anticipate and to adapt to the sustained daily changes in ambient illumination. Using a combination of laser capture micro-dissection and quantitative PCR in the present study, the clockwork of mammalian photoreceptors has been recorded. The transcript amounts of the core clock genes Clock, Bmal1, Period1 (Per1), Per3, Cryptochrome2, and Casein kinase Ie in photoreceptors of rat retina have been found to undergo daily changes. Clock and Bmal1 peak with Per1 and Per3 around dark onset, whereas Casein kinase Ie and Cryptochrome2 peak at night…
Influence of photoperiodic history on clock genes and the circadian pacemaker in the rat retina
2006
The influence of seasonal lighting conditions on expression of clock genes and the circadian pacemaker was investigated in the rat retina. For this purpose, the 24-h profiles of nine clock genes (bmal1, clock, per1, per2, per3, dec1, dec2, cry1 and cry 2) and the arylalkylamine N-acetyltransferase gene as an indicator of the circadian pacemaker output were compared between light-dark periods of 8 : 16 and 16 : 8 h. The photoperiod influenced the daily patterns of the amount of transcript for per1, per3, dec2 and arylalkylamine N-acetyltransferase. This indicates that photoperiodic information modulates clock gene expression in addition to the circadian pacemaker of the retina. Under constan…
Plasticity of retinal ribbon synapses.
1996
Ribbon synapses differ from conventional chemical synapses in that they contain, within the cloud of synaptic vesicles (SV's), a specialized synaptic body, most often termed synaptic ribbon (SR). This body assumes various forms. Reconstructions reveal that what appear as rod- or ribbon-like profiles in sections are in fact rectangular or horseshoe-shaped plates. Moreover, spherical, T-shaped, table-shaped, and highly pleomorphic bodies may be present. In mammals, ribbon synapses are present in afferent synapses of photoreceptors, bipolar nerve cells, and hair cells of both the organ of Corti and the vestibular organ. Synaptic ribbons (SR's) are also found in the intrinsic cells of the third…
Phosphodiesterase 10A in the Rat Pineal Gland: Localization, Daily and Seasonal Regulation of Expression and Influence on Signal Transduction
2010
The cyclic nucleotide phosphodiesterase 10A (PDE10A) is highly expressed in striatal spiny projection neurons and represents a therapeutic target for the treatment of psychotic symptoms. As reported previously [J Biol Chem 2009; 284:7606–7622], in this study PDE10A was seen to be additionally expressed in the pineal gland where the levels of PDE10A transcript display daily changes. As with the transcript, the amount of PDE10A protein was found to be under daily and seasonal regulation. The observed cyclicity in the amount of PDE10A mRNA persists under constant darkness, is blocked by constant light and is modulated by the lighting regime. It therefore appears to be driven by the master cloc…
Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin I
2011
Synaptic transmission relies on effective and accurate compensatory endocytosis. F-BAR proteins may serve as membrane curvature sensors and/or inducers and thereby support membrane remodelling processes; yet, their in vivo functions urgently await disclosure. We demonstrate that the F-BAR protein syndapin I is crucial for proper brain function. Syndapin I knockout (KO) mice suffer from seizures, a phenotype consistent with excessive hippocampal network activity. Loss of syndapin I causes defects in presynaptic membrane trafficking processes, which are especially evident under high-capacity retrieval conditions, accumulation of endocytic intermediates, loss of synaptic vesicle (SV) size cont…
Phosphodiesterase10A: abundance and circadian regulation in the retina and photoreceptor of the rat.
2011
Phosphodiesterase10A (PDE10A) is a dual specific cyclic nucleotide phosphodiesterase that is specifically enriched in striatum and which has gained attention as a therapeutic target for psychiatric disorders. The present study shows that PDE10A is also highly expressed in retinal neurons including photoreceptors. The levels of PDE10A transcript and protein display daily rhythms which could be seen in preparations of the whole retina. Corresponding changes in PDE10A mRNA were seen in photoreceptors isolated using laser microdissection. This suggests that the expressional control of the photoreceptor Pde10a gene contributes to the observed cyclicity in the amount of retinal PDE10A. The daily …