Version 1
: Received: 26 October 2023 / Approved: 26 October 2023 / Online: 27 October 2023 (07:16:08 CEST)
Version 2
: Received: 28 November 2023 / Approved: 28 November 2023 / Online: 29 November 2023 (09:43:31 CET)
Vivi, E.; Seeholzer, L.R.; Nagumanova, A.; Di Benedetto, B. 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. Cells2023, 12, 2761.
Vivi, E.; Seeholzer, L.R.; Nagumanova, A.; Di Benedetto, B. 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 2023, 12, 2761.
Vivi, E.; Seeholzer, L.R.; Nagumanova, A.; Di Benedetto, B. 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. Cells2023, 12, 2761.
Vivi, E.; Seeholzer, L.R.; Nagumanova, A.; Di Benedetto, B. 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 2023, 12, 2761.
Abstract
Clinical and pre-clinical studies of neuropsychiatric (NP) disorders show altered astrocyte prop-erties and synaptic networks. These are refined during early postnatal developmental (PND) stages. Therefore, 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 for the refinement of 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 syn-aptophysin and PSD95 in the cortex of developing pups. We then combined immunofluores-cent-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 needed to use OBSCs to reveal sex-dependent differences. In conclusion, OBSCs can be a valid model to study physiological as-trocyte-mediated synaptic remodelling during PND and might be exploited to investigate pathomechanisms of brain disorders with aberrant synaptic development.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
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