@phdthesis{Nguyen2023,
  author    = {Nguyen, Tu Anh Thi},
  title     = {Neural coding of different visual cues in the monarch butterfly sun compass},
  doi       = {10.25972/OPUS-30380},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303807},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {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.},
  subject      = {Monarchfalter},
  language  = {en}
}
@article{SchadtIsraelBeezetal.2023,
  author    = {Schadt, Fabian and Israel, Ina and Beez, Alexandra and Alushi, Kastriot and Weiland, Judith and Ernestus, Ralf-Ingo and Westermaier, Thomas and Samnick, Samuel and Lilla, Nadine},
  title     = {Analysis of cerebral glucose metabolism following experimental subarachnoid hemorrhage over 7 days},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-022-26183-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300725},
  year      = {2023},
  abstract  = {Little is known about changes in brain metabolism following SAH, possibly leading towards secondary brain damage. Despite sustained progress in the last decade, analysis of in vivo acquired data still remains challenging. The present interdisciplinary study uses a semi-automated data analysis tool analyzing imaging data independently from the administrated radiotracer. The uptake of 2-[18F]Fluoro-2-deoxy-glucose ([\(^{18}\)F]FDG) was evaluated in different brain regions in 14 male Sprague-Dawley rats, randomized into two groups: (1) SAH induced by the endovascular filament model and (2) sham operated controls. Serial [\(^{18}\)F]FDG-PET measurements were carried out. Quantitative image analysis was performed by uptake ratio using a self-developed MRI-template based data analysis tool. SAH animals showed significantly higher [\(^{18}\)F]FDG accumulation in gray matter, neocortex and olfactory system as compared to animals of the sham group, while white matter and basal forebrain region showed significant reduced tracer accumulation in SAH animals. All significant metabolic changes were visualized from 3 h, over 24 h (day 1), day 4 and day 7 following SAH/sham operation. This [\(^{18}\)F]FDG-PET study provides important insights into glucose metabolism alterations following SAH—for the first time in different brain regions and up to day 7 during course of disease.},
  language  = {en}
}
@article{FeldheimWendLaueretal.2022,
  author    = {Feldheim, Jonas and Wend, David and Lauer, Mara J. and Monoranu, Camelia M. and Glas, Martin and Kleinschnitz, Christoph and Ernestus, Ralf-Ingo and Braunger, Barbara M. and Meybohm, Patrick and Hagemann, Carsten and Burek, Malgorzata},
  title     = {Protocadherin Gamma C3 (PCDHGC3) is strongly expressed in glioblastoma and its high expression is associated with longer progression-free survival of patients},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {15},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23158101},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284433},
  year      = {2022},
  abstract  = {Protocadherins (PCDHs) belong to the cadherin superfamily and represent the largest subgroup of calcium-dependent adhesion molecules. In the genome, most PCDHs are arranged in three clusters, α, β, and γ on chromosome 5q31. PCDHs are highly expressed in the central nervous system (CNS). Several PCDHs have tumor suppressor functions, but their individual role in primary brain tumors has not yet been elucidated. Here, we examined the mRNA expression of PCDHGC3, a member of the PCDHγ cluster, in non-cancerous brain tissue and in gliomas of different World Health Organization (WHO) grades and correlated it with the clinical data of the patients. We generated a PCDHGC3 knockout U343 cell line and examined its growth rate and migration in a wound healing assay. We showed that PCDHGC3 mRNA and protein were significantly overexpressed in glioma tissue compared to a non-cancerous brain specimen. This could be confirmed in glioma cell lines. High PCDHGC3 mRNA expression correlated with longer progression-free survival (PFS) in glioma patients. PCDHGC3 knockout in U343 resulted in a slower growth rate but a significantly faster migration rate in the wound healing assay and decreased the expression of several genes involved in WNT signaling. PCDHGC3 expression should therefore be further investigated as a PFS-marker in gliomas. However, more studies are needed to elucidate the molecular mechanisms underlying the PCDHGC3 effects.},
  language  = {en}
}
@article{HabensteinSchmittLiessemetal.2021,
  author    = {Habenstein, Jens and Schmitt, Franziska and Liessem, Sander and Ly, Alice and Trede, Dennis and Wegener, Christian and Predel, Reinhard and R{\"o}ssler, Wolfgang and Neupert, Susanne},
  title     = {Transcriptomic, peptidomic, and mass spectrometry imaging analysis of the brain in the ant Cataglyphis nodus},
  series = {Journal of Neurochemistry},
  volume    = {158},
  journal   = {Journal of Neurochemistry},
  number    = {2},
  doi       = {10.1111/jnc.15346},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239917},
  pages     = {391 -- 412},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@article{UeceylerBuchholzKewenigetal.2020,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Buchholz, Hans-Georg and Kewenig, Susanne and Ament, Stephan-Johann and Birklein, Frank and Schreckenberger, Mathias and Sommer, Claudia},
  title     = {Cortical Binding Potential of Opioid Receptors in Patients With Fibromyalgia Syndrome and Reduced Systemic Interleukin-4 Levels - A Pilot Study},
  series = {Frontiers in Neuroscience},
  volume    = {14},
  journal   = {Frontiers in Neuroscience},
  issn      = {1662-453X},
  doi       = {10.3389/fnins.2020.00512},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204457},
  year      = {2020},
  abstract  = {Objective: We investigated cerebral opioid receptor binding potential in patients with fibromyalgia syndrome (FMS) using positron-emission-tomography (PET) and correlated our results with patients' systemic interleukin-4 (IL-4) gene expression. Methods: In this pilot study, seven FMS patients (1 man, 6 women) agreed to participate in experimental PET scans. All patients underwent neurological examination, were investigated with questionnaires for pain, depression, and FMS symptoms. Additionally, blood for IL-4 gene expression analysis was withdrawn at two time points with a median latency of 1.3 years. Patients were investigated in a PET scanner using the opioid receptor ligand F-18-fluoro-ethyl-diprenorphine ([18F]FEDPN) and results were compared with laboratory normative values. Results: Neurological examination was normal in all FMS patients. Reduced opioid receptor binding was found in mid cingulate cortex compared to healthy controls (p < 0.005). Interestingly, three patients with high systemic IL-4 gene expression had increased opioid receptor binding in the fronto-basal cortex compared to those with low IL-4 gene expression (p < 0.005). Conclusion: Our data give further evidence for a reduction in cortical opioid receptor availability in FMS patients as another potential central nervous system contributor to pain in FMS.},
  language  = {en}
}
@article{BrumbergSchroeterBlazhenetsetal.2020,
  author    = {Brumberg, Joachim and Schr{\"o}ter, Nils and Blazhenets, Ganna and Frings, Lars and Volkmann, Jens and Lapa, Constantin and Jost, Wolfgang H. and Isaias, Ioannis U. and Meyer, Philipp T.},
  title     = {Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy},
  series = {NPJ Parkinsons Disease},
  volume    = {6},
  journal   = {NPJ Parkinsons Disease},
  doi       = {10.1038/s41531-020-00141-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230675},
  year      = {2020},
  abstract  = {[\(^{18}\)F]fluorodeoxyglucose (FDG) PET and [\(^{123}\)I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 +/- 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson's disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator \#1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater \#1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred.},
  language  = {en}
}
@article{Koepsell2020,
  author    = {Koepsell, Hermann},
  title     = {Glucose transporters in brain in health and disease},
  series = {Pfl{\"u}gers Archiv - European Journal of Physiology},
  volume    = {472},
  journal   = {Pfl{\"u}gers Archiv - European Journal of Physiology},
  issn      = {0031-6768},
  doi       = {10.1007/s00424-020-02441-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232746},
  pages     = {1299-1343},
  year      = {2020},
  abstract  = {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},
  language  = {en}
}
@article{FeldheimKesslerSchmittetal.2020,
  author    = {Feldheim, Jonas and Kessler, Almuth F. and Schmitt, Dominik and Salvador, Ellaine and Monoranu, Camelia M. and Feldheim, Julia J. and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Hagemann, Carsten},
  title     = {Ribosomal Protein S27/Metallopanstimulin-1 (RPS27) in Glioma — A New Disease Biomarker?},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {5},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12051085},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203648},
  year      = {2020},
  abstract  = {Despite its significant overexpression in several malignant neoplasms, the expression of RPS27 in the central nervous system (CNS) is widely unknown. We identified the cell types expressing RPS27 in the CNS under normal and disease conditions. We acquired specimens of healthy brain (NB), adult pilocytic astrocytoma (PA) World Health Organization (WHO) grade I, anaplastic PA WHO grade III, gliomas WHO grade II/III with or without isocitrate dehydrogenase (IDH) mutation, and glioblastoma multiforme (GBM). RPS27 protein expression was examined by immunohistochemistry and double-fluorescence staining and its mRNA expression quantified by RT-PCR. Patients' clinical and tumor characteristics were collected retrospectively. RPS27 protein was specifically expressed in tumor cells and neurons, but not in healthy astrocytes. In tumor tissue, most macrophages were positive, while this was rarely the case in inflamed tissue. Compared to NB, RPS27 mRNA was in mean 6.2- and 8.8-fold enhanced in gliomas WHO grade II/III with (p < 0.01) and without IDH mutation (p = 0.01), respectively. GBM displayed a 4.6-fold increased mean expression (p = 0.02). Although RPS27 expression levels did not affect the patients' survival, their association with tumor cells and tumor-associated macrophages provides a rationale for a future investigation of a potential function during gliomagenesis and tumor immune response.},
  language  = {en}
}
@article{ThoelkenThammErbacheretal.2019,
  author    = {Th{\"o}lken, Clemens and Thamm, Markus and Erbacher, Christoph and Lechner, Marcus},
  title     = {Sequence and structural properties of circular RNAs in the brain of nurse and forager honeybees (Apis mellifera)},
  series = {BMC Genomics},
  volume    = {20},
  journal   = {BMC Genomics},
  doi       = {10.1186/s12864-018-5402-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241302},
  year      = {2019},
  abstract  = {Background The honeybee (Apis mellifera) represents a model organism for social insects displaying behavioral plasticity. This is reflected by an age-dependent task allocation. The most protruding tasks are performed by young nurse bees and older forager bees that take care of the brood inside the hive and collect food from outside the hive, respectively. The molecular mechanism leading to the transition from nurse bees to foragers is currently under intense research. Circular RNAs, however, were not considered in this context so far. As of today, this group of non-coding RNAs was only known to exist in two other insects, Drosophila melanogaster and Bombyx mori. Here we complement the state of circular RNA research with the first characterization in a social insect. Results We identified numerous circular RNAs in the brain of A. mellifera nurse bees and forager bees using RNA-Seq with exonuclease enrichment. Presence and circularity were verified for the most abundant representatives. Back-splicing in honeybee occurs further towards the end of transcripts and in transcripts with a high number of exons. The occurrence of circularized exons is correlated with length and CpG-content of their flanking introns. The latter coincides with increased DNA-methylation in the respective loci. For two prominent circular RNAs the abundance in worker bee brains was quantified in TaqMan assays. In line with previous findings of circular RNAs in Drosophila, circAmrsmep2 accumulates with increasing age of the insect. In contrast, the levels of circAmrad appear age-independent and correlate with the bee's task. Its parental gene is related to amnesia-resistant memory. Conclusions We provide the first characterization of circRNAs in a social insect. Many of the RNAs identified here show homologies to circular RNAs found in Drosophila and Bombyx, indicating that circular RNAs are a common feature among insects. We find that exon circularization is correlated to DNA-methylation at the flanking introns. The levels of circAmrad suggest a task-dependent abundance that is decoupled from age. Moreover, a GO term analysis shows an enrichment of task-related functions. We conclude that circular RNAs could be relevant for task allocation in honeybee and should be investigated further in this context.},
  language  = {en}
}
@article{HibarAdamsJahanshadetal.2017,
  author    = {Hibar, Derrek P. and Adams, Hieab H.H. and Jahanshad, Neda and Chauhan, Ganesh and Stein, Jason L and Hofer, Edith and Renteria, Miguel E. and Bis, Joshua C. and Arias-Vasquez, Alejandro and Ikram, M. Kamran and Desrivi{\`e}res, Sylvane and Vernooij, Meike W. and Abramovic, Lucija and Alhusaini, Saud and Amin, Najaf and Andersson, Micael and Arfanakis, Konstantinos and Aribisala, Benjamin S. and Armstrong, Nicola J. and Athanasiu, Lavinia and Axelsson, Tomas and Beecham, Ashley H. and Beiser, Alexa and Bernard, Manon and Blanton, Susan H. and Bohlken, Marc M. and Boks, Marco P. and Bralten, Janita and Brickman, Adam M. and Carmichael, Owen},
  title     = {Novel genetic loci associated with hippocampal volume},
  series = {Nature Communications},
  volume    = {8},
  journal   = {Nature Communications},
  doi       = {10.1038/ncomms13624},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-182115},
  pages     = {12},
  year      = {2017},
  abstract  = {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.},
  language  = {en}
}