Refine
Has Fulltext
- yes (34)
Is part of the Bibliography
- yes (34)
Year of publication
Document Type
- Journal article (30)
- Doctoral Thesis (4)
Keywords
- brain (34) (remove)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (7)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (5)
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie (4)
- Neurochirurgische Klinik und Poliklinik (4)
- Pathologisches Institut (4)
- Institut für Anatomie und Zellbiologie (3)
- Institut für Psychologie (3)
- Neurologische Klinik und Poliklinik (3)
- Graduate School of Life Sciences (2)
- Klinik und Poliklinik für Anästhesiologie (ab 2004) (2)
Background: Localization of mRNAs encoding cytoskeletal or signaling proteins to neuronal processes is known to contribute to axon growth, synaptic differentiation and plasticity. In addition, a still increasing spectrum of mRNAs has been demonstrated to be localized under different conditions and developing stages thus reflecting a highly regulated mechanism and a role of mRNA localization in a broad range of cellular processes.
Results: Applying fluorescence in-situ-hybridization with specific riboprobes on cultured neurons and nervous tissue sections, we investigated whether the mRNAs for two metabolic enzymes, namely glycogen synthase (GS) and glycogen phosphorylase (GP), the key enzymes of glycogen metabolism, may also be targeted to neuronal processes. If it were so, this might contribute to clarify the so far enigmatic role of neuronal glycogen. We found that the mRNAs for both enzymes are localized to axonal and dendritic processes in cultured lumbar spinal motoneurons, but not in cultured trigeminal neurons. In cultured cortical neurons which do not store glycogen but nevertheless express glycogen synthase, the GS mRNA is also subject to axonal and dendritic localization. In spinal motoneurons and trigeminal neurons in situ, however, the mRNAs could only be demonstrated in the neuronal somata but not in the nerves.
Conclusions: We could demonstrate that the mRNAs for major enzymes of neural energy metabolism can be localized to neuronal processes. The heterogeneous pattern of mRNA localization in different culture types and developmental stages stresses that mRNA localization is a versatile mechanism for the fine-tuning of cellular events. Our findings suggest that mRNA localization for enzymes of glycogen metabolism could allow adaptation to spatial and temporal energy demands in neuronal events like growth, repair and synaptic transmission.
Monarch butterflies are famous for their annual long-distance migration. Decreasing temperatures and reduced daylight induce the migratory state in the autumn generation of monarch butterflies. Not only are they in a reproductive diapause, they also produce fat deposits to be prepared for the upcoming journey: Driven by their instinct to migrate, they depart from their eclosion grounds in the northern regions of the North American continent and start their southern journey to their hibernation spots in Central Mexico. The butterflies cover a distance of up to 4000 km across the United States. In the next spring, the same butterflies invert their preferred heading direction due to seasonal changes and start their northward spring migration. The spring migration is continued by three consecutive butterfly generations, until the animals repopulate the northern regions in North America as non-migratory monarch butterflies. The monarch butterflies’ migratory state is genetically and epigenetically regulated, including the directed flight behavior. Therefore, the insect’s internal compass system does not only have to encode the butterflies preferred, but also its current heading direction. However, the butterfly’s internal heading representation has to be matched to external cues, to avoid departing from its initial flight path and increasing its risk of missing its desired destination. During the migratory flight, visual cues provide the butterflies with reliable orientation information. The butterflies refer to the sun as their main orientation cue. In addition to the sun, the butterflies likely use the polarization pattern of the sky for orientation. The sky compass signals are processed within a region in the brain, termed the central complex (CX). Previous research on the CX neural circuitry of the monarch butterflies demonstrated that tangential central complex neurons (TL) carry the visual input information into the CX and respond to a simulated sun and polarized light. However, whether these cells process additional visual cues like the panoramic skyline is still unknown. Furthermore, little is known about how the migratory state affects visual cue processing. In addition to this, most experiments studying the monarch butterfly CX focused on how neurons process single visual cues. However, how combined visual stimuli are processed in the CX is still unknown.
This thesis is investigating the following questions:
1) How does the migratory state affect visual cue processing in the TL cells within the monarch butterfly brain?
2) How are multiple visual cues integrated in the TL cells?
3) How is compass information modulated in the CX?
To study these questions, TL neurons from both animal groups (migratory and non-migratory) were electrophysiologically characterized using intracellular recordings while presenting different simulated celestial cues and visual sceneries. I showed that the TL neurons of migratory butterflies are more narrowly tuned to the sun, possibly helping them in keeping a directed flight course during migration. Furthermore, I found that TL cells encode a panoramic skyline, suggesting that the CX network combines celestial and terrestrial information. Experiments with combined celestial stimuli revealed that the TL cells combine both cue information linearly. However, if exposing the animals to a simulated visual scenery containing a panoramic skyline and a simulated sun, the single visual cues are weighted differently. These results indicate that the CX’s input region can flexibly adapt to different visual cue conditions. Furthermore, I characterize a previously unknown neuron in the monarch butterfly CX which responds to celestial stimuli and connects the CX with other brain neuropiles. How this cell type affects heading direction encoding has yet to be determined.
In our current obesogenic environment, exposure to visual food-cues can easily lead to craving and overeating because short-term, pleasurable effects of food intake dominate over the anticipated long-term adverse effects such as weight gain and associated health problems. Here we contrasted these two conditions during food-cue presentation while acquiring event-related potentials (ERPs) and subjective craving ratings. Female participants (n = 25) were presented with either high-calorie (HC) or low-calorie (LC) food images under instructions to imagine either immediate (NOW) or long-term effects (LATER) of consumption. On subjective ratings for HC foods, the LATER perspective reduced cravings as compared to the NOW perspective. For LC foods, by contrast, craving increased under the LATER perspective. Early ERPs (occipital N1, 150-200 ms) were sensitive to food type but not to perspective. Late ERPs (late positive potential, LPP, 350-550 ms) were larger in the HC-LATER condition than in all other conditions, possibly indicating that a cognitive focus on negative long-term consequences induced negative arousal. This enhancement for HC-LATER attenuated to the level of the LC conditions during the later slow wave (550-3000 ms), but amplitude in the HC-NOW condition was larger than in all other conditions, possibly due to a delayed appetitive response. Across all conditions, LPP amplitudes were positively correlated with self-reported emotional eating. In sum, results reveal that regulation effects are secondary to an early attentional analysis of food type and dynamically evolve over time. Adopting a long-term perspective on eating might promote a healthier food choice across a range of food types.
Das humane Chromosom 15 wurde bereits im Zusammenhang mit anderen Erkrankungen wie dem Marfan Syndrom und der Tay Sachs Erkrankung erwähnt. Für deren Genese wurden auf dem Chromosom gelegene Gene verantwortlich gemacht (Richard et al. 1994). Aufbauend auf den Vorarbeiten der Würzburger Arbeitsgruppe (Stöber et al. 2000, 2002; Meyer et al. 2002) wurden auf Chromosom 15 anhand der Lokalisation, der Funktion und dem Vorhandensein im Zentralnervensystem die Gene Cx36 und TYRO3 für die Mutationsanalyse ausgewählt, um sie nach der Methode von Sanger (Sanger et al. 1977) zu sequenzieren. Sowohl Cx36 als auch TYRO3 spielen eine zentrale Rolle in der Entwicklung und Zellinteraktion im ZNS. Es wäre denkbar, daß ein Defekt während der Synaptogenese im ZNS an der Krankheitsentstehung beteiligt ist, ebenso wie eine unzureichende Ausbildung von Gap junctions, an denen Cx36 maßgeblich beteiligt ist. Die Patienten-DNA wurde aus Blutproben von Probanden mit periodischer Katatonie gewonnen. Diese wurden aus der Familie 11 der bereits erwähnten Studie rekrutiert, die in drei Generationen von der Erkrankung betroffen ist und zehn gesunde, sowie 7 kranke Mitglieder zählt. Die Proben wurden zusammen mit solchen von gesunden Kontrollpersonen vergleichend sequenziert und auf Übereinstimmung mit den Einträgen der GenBank überprüft mit dem Ziel, Mutationen zu finden, die zu einem Defekt im Protein führen und zur Ausprägung der Krankheit beitragen, bzw. die Gene als Kandidaten auszuschließen.
The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities\((P_{comb}=7.71 x 10^{-10}, n=699)\), with an effect size of 4.87%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.
Energy demand of neurons in brain that is covered by glucose supply from the blood is ensured by glucose transporters incapillaries and brain cells. In brain, the facilitative diffusion glucose transporters GLUT1-6 and GLUT8, and the Na+-D-glucosecotransporters SGLT1 are expressed. The glucose transporters mediate uptake of D-glucose across the blood-brain barrier anddelivery of D-glucose to astrocytes and neurons. They are critically involved in regulatory adaptations to varying energy demandsin response to differing neuronal activities and glucose supply. In this review, a comprehensive overview about verified andproposed roles of cerebral glucose transporters during health and diseases is presented. Our current knowledge is mainly based onexperiments performed in rodents. First, the functional properties of human glucose transporters expressed in brain and theircerebral locations are described. Thereafter, proposed physiological functions of GLUT1, GLUT2, GLUT3, GLUT4, andSGLT1 for energy supply to neurons, glucose sensing, central regulation of glucohomeostasis, and feeding behavior are compiled, and their roles in learning and memory formation are discussed. In addition, diseases are described in which functionalchanges of cerebral glucose transporters are relevant. These are GLUT1 deficiency syndrome (GLUT1-SD), diabetes mellitus, Alzheimer’s disease (AD), stroke, and traumatic brain injury (TBI). GLUT1-SD is caused by defect mutations in GLUT1. Diabetes and AD are associated with changed expression of glucose transporters in brain, and transporter-related energy defi-ciency of neurons may contribute to pathogenesis of AD. Stroke and TBI are associated with changes of glucose transporter expression that influence clinical outcome
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease (r\(_g\)=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Background: Data from clinical studies and results from animal models suggest an involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment.
Methods: We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples.
Results: In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects (\(P_{corr}\) = .018, \(P_{corr}\) = .015 and \(P_{corr}\) = .004, respectively). We observed an across-gene BDNF-NTRK2 SNP interaction for rs4923468 and rs1387926. No robust interaction of associated SNPs was found in an analysis of BDNF serum protein levels as a predictor for treatment outcome in a subset of 93 patients.
Conclusions/Limitations: Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the BDNF and NTRK2 genes that might be involved in antidepressant treatment outcome and that have not been previously reported in this context. These new variants need further validation in future association studies.
The Behavioral Inhibition System (BIS) as defined within the Reinforcement Sensitivity Theory (RST) modulates reactions to stimuli indicating aversive events. Gray's trait Anxiety determines the extent to which stimuli activate the BIS. While studies have identified the amygdala-septo-hippocampal circuit as the key-neural substrate of this system in recent years and measures of resting-state dynamics such as randomness and local synchronization of spontaneous BOLD fluctuations have recently been linked to personality traits, the relation between resting-state dynamics and the BIS remains unexplored. In the present study, we thus examined the local synchronization of spontaneous fMRI BOLD fluctuations as measured by Regional Homogeneity (ReHo) in the hippocampus and the amygdala in twenty-seven healthy subjects. Correlation analyses showed that Gray's trait Anxiety was significantly associated with mean ReHo in both the amygdala and the hippocampus. Specifically, Gray's trait Anxiety explained 23% and 17% of resting-state ReHo variance in the left amygdala and the left hippocampus, respectively. In summary, we found individual differences in Gray's trait Anxiety to be associated with ReHo in areas previously associated with BIS functioning. Specifically, higher ReHo in resting-state neural dynamics corresponded to lower sensitivity to punishment scores both in the amygdala and the hippocampus. These findings corroborate and extend recent findings relating resting-state dynamics and personality while providing first evidence linking properties of resting-state fluctuations to Gray's BIS.
Behavioral flexibility is an important cornerstone for the ecological success of animals. Social Cataglyphis nodus ants with their age‐related polyethism characterized by age‐related behavioral phenotypes represent a prime example for behavioral flexibility. We propose neuropeptides as powerful candidates for the flexible modulation of age‐related behavioral transitions in individual ants. As the neuropeptidome of C. nodus was unknown, we collected a comprehensive peptidomic data set obtained by transcriptome analysis of the ants’ central nervous system combined with brain extract analysis by Q‐Exactive Orbitrap mass spectrometry (MS) and direct tissue profiling of different regions of the brain by matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) MS. In total, we identified 71 peptides with likely bioactive function, encoded on 49 neuropeptide‐, neuropeptide‐like, and protein hormone prepropeptide genes, including a novel neuropeptide‐like gene (fliktin). We next characterized the spatial distribution of a subset of peptides encoded on 16 precursor proteins with high resolution by MALDI MS imaging (MALDI MSI) on 14 µm brain sections. The accuracy of our MSI data were confirmed by matching the immunostaining patterns for tachykinins with MSI ion images from consecutive brain sections. Our data provide a solid framework for future research into spatially resolved qualitative and quantitative peptidomic changes associated with stage‐specific behavioral transitions and the functional role of neuropeptides in Cataglyphis ants.