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| 001 | 281739 | ||
| 005 | 20251013134308.0 | ||
| 037 | _ | _ | |a DZNE-2025-01172 |
| 100 | 1 | _ | |a Gockel, Nala Eileen |0 P:(DE-2719)9002002 |b 0 |u dzne |
| 245 | _ | _ | |a Mechanisms of microglia-mediated synapse formation and elimination |
| 260 | _ | _ | |c 2025 |
| 300 | _ | _ | |a 112 pp. |
| 336 | 7 | _ | |a Output Types/Dissertation |2 DataCite |
| 336 | 7 | _ | |a DISSERTATION |2 ORCID |
| 336 | 7 | _ | |a PHDTHESIS |2 BibTeX |
| 336 | 7 | _ | |a Thesis |0 2 |2 EndNote |
| 336 | 7 | _ | |a Dissertation / PhD Thesis |b phd |m phd |0 PUB:(DE-HGF)11 |s 1760355662_8169 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a doctoralThesis |2 DRIVER |
| 502 | _ | _ | |a Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn, 2025 |c Rheinische Friedrich-Wilhelms-Universität Bonn |b Dissertation |d 2025 |
| 520 | _ | _ | |a Early impairments at the synaptic level can lead to disruption of communication between neurons, triggering neurological diseases such as schizophrenia. Emerging evidence has identified microglia as a key player in shaping synaptic architecture, but the precise mechanisms remain insufficiently understood.This study aims to investigate mechanisms of microglia-mediated synapse formation and elimination in two physiological contexts: first, during postnatal development, targeting microglia-complement interactions and second, during adult homeostasis examining microglia-synapse crosstalk via neurotransmitter signaling.The first objective used two-photon in vivo imaging to assess changes in synaptic density, microglial surveillance dynamics and microglia-synapse contact rates in a mouse model of complement protein overexpression, recapitulating hallmark phenotypes of schizophrenia. A complement receptor knock-out demonstrated to mediate synaptic density deficits and deficiency in microglia-synapse contacts after upregulation of complement proteins, potentially via a lack in spine formation. Specifically, the microglial iC3b-CR3 pathway was identified as a potential therapeutic target in schizophrenia research.The second objective targeted microglia-presynapse communication in the adult hippocampus with a microglia specific knock-out of a cholinergic neurotransmitter receptor. Awake two-photon calcium imaging of presynaptic boutons in combination with microglial dynamics revealed high microglia surveillance of putative active boutons. This suggested possible activity-dependent synapse remodeling by microglia in the adult brain. Microglia motility in a cholinergic receptor knock-out was altered upon distinct stimulation paradigms of neuronal projections. This identified the microglial α7 nicotinic acetylcholine receptor as a potential modulator of structural synaptic plasticity by sensing excess neurotransmitter release.Lastly, two-photon STED imaging was introduced enabling high-resolution in vivo imaging of nanoscale structures offering potential for future insights into active microglial synapse formation and elimination.These findings suggest microglia to have a central role in modulating synaptic densities, both in development, as well as in adulthood, via complement and neurotransmitter signaling, in health and disease. Microglial heterogeneity and context-dependency highlighted the importance to maintain a homeostatic balance between neurons and microglia to prevent cognitive impairments throughout life. |
| 536 | _ | _ | |a 352 - Disease Mechanisms (POF4-352) |0 G:(DE-HGF)POF4-352 |c POF4-352 |f POF IV |x 0 |
| 856 | 4 | _ | |u https://pub.dzne.de/record/281739/files/DZNE-2025-01172_Restricted.pdf |
| 856 | 4 | _ | |u https://pub.dzne.de/record/281739/files/DZNE-2025-01172_Restricted.pdf?subformat=pdfa |x pdfa |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 0 |6 P:(DE-2719)9002002 |
| 913 | 1 | _ | |a DE-HGF |b Gesundheit |l Neurodegenerative Diseases |1 G:(DE-HGF)POF4-350 |0 G:(DE-HGF)POF4-352 |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-300 |4 G:(DE-HGF)POF |v Disease Mechanisms |x 0 |
| 914 | 1 | _ | |y 2025 |
| 920 | 1 | _ | |0 I:(DE-2719)1011004 |k AG Fuhrmann |l Neuroimmunology and Imaging |x 0 |
| 980 | _ | _ | |a phd |
| 980 | _ | _ | |a EDITORS |
| 980 | _ | _ | |a VDBINPRINT |
| 980 | _ | _ | |a I:(DE-2719)1011004 |
| 980 | _ | _ | |a UNRESTRICTED |
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