Vivi, Eugenia and Seeholzer, Lea R. and Nagumanova, Anastasiia and Di Benedetto, Barbara (2023) Early Age- and Sex-Dependent Regulation of Astrocyte-Mediated Glutamatergic Synapse Elimination in the Rat Prefrontal Cortex: Establishing an Organotypic Brain Slice Culture Investigating Tool. CELLS, 12 (23): 2761. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)Abstract
Clinical and pre-clinical studies of neuropsychiatric (NP) disorders show altered astrocyte properties and synaptic networks. These are refined during early postnatal developmental (PND) stages. Thus, investigating early brain maturational trajectories is essential to understand NP disorders. However, animal experiments are highly time-/resource-consuming, thereby calling for alternative methodological approaches. The function of MEGF10 in astrocyte-mediated synapse elimination (pruning) is crucial to refine neuronal networks during development and adulthood. To investigate the impact of MEGF10 during PND in the rat prefrontal cortex (PFC) and its putative role in brain disorders, we established and validated an organotypic brain slice culture (OBSC) system. Using Western blot, we characterized the expression of MEGF10 and the synaptic markers synaptophysin and PSD95 in the cortex of developing pups. We then combined immunofluorescent-immunohistochemistry with Imaris-supported 3D analysis to compare age- and sex-dependent astrocyte-mediated pruning within the PFC in pups and OBSCs. We thereby validated this system to investigate age-dependent astrocyte-mediated changes in pruning during PND. However, further optimizations are required to use OBSCs for revealing sex-dependent differences. In conclusion, OBSCs offer a valid alternative to study physiological astrocyte-mediated synaptic remodeling during PND and might be exploited to investigate the pathomechanisms of brain disorders with aberrant synaptic development.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENETIC ARCHITECTURE; MEGF10; CELLS; ADOLESCENCE; TRANSITION; MATURATION; PATHOLOGY; RECEPTOR; DENSITY; NEURONS; organotypic brain slice culture; astrocyte; synaptic phagocytosis; critical period; sex differences |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Mar 2024 11:38 |
| Last Modified: | 07 Mar 2024 11:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58899 |
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