Astrocytic diazepam binding inhibitor instructs microglial synaptic engulfment in Lewy body dementia

Cui, Mochen (2023): Astrocytic diazepam binding inhibitor instructs microglial synaptic engulfment in Lewy body dementia. Dissertation, LMU München: Medizinische Fakultät

Abstract

In Lewy body dementia (LBD), loss of synapses is associated with reactive astrocytes and activated microglia. However, the interaction between these two major glial cell types and the subsequent implications on synaptic removal remain unclear. This study demonstrates that anomalous secretion of astrocyte-derived diazepam binding inhibitor (DBI), an endogenous ligand of the 18 kDa translocator protein (TSPO), facilitates excessive microglial phagocytosis of synaptic materials in a mouse model of LBD and in postmortem brains of patients with LBD-associated dementia. Additionally, evidence is presented suggesting that the decline of synaptic plasticity in LBD-associated dementia is dependent on the astrocytic DBI-microglial TSPO signaling pathway, as it can be mitigated by DBI knock-down or TSPO knock-out. These findings emphasize the significance of astrocyte-microglia interaction in regulating synaptic plasticity and propose the non-neuronal DBI-TSPO signaling pathway between these glial cells as potential therapeutic targets to improve synaptic pathology in LBD-associated dementia.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Lewy body dementia, astrocyte, microglia, dendritic spines, TSPO, DBI
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 21. November 2023
• 1. Bericht­erstatter:in: Herms, Jochen