Published June 23, 2023
| Version v1
Publication
Microglial Caspase-3 is essential for modulating hippocampal neurogenesis.
Description
Adult hippocampal neurogenesis (AHN) is a process involved in numerous neurodegenerative diseases. Many
researchers have described microglia as a key component in regulating the formation and migration of new
neurons along the rostral migratory stream. Caspase-3 is a cysteine-aspartate-protease classically considered as
one of the main effector caspases in the cell death program process. In addition to this classical function, we have
identified the role of this protein as a modulator of microglial function; however, its action on neurogenic
processes is unknown. The aim of the present study is to identify the role of Caspase-3 in neurogenesis-related
microglial functions. To address this study, Caspase-3 conditional knockout mice in the microglia cell line
were used. Using this tool, we wanted to elucidate the role of this protein in microglial function in the hippocampus, the main region in which adult neurogenesis takes place. After the reduction of Caspase-3 in microglia,
mutant mice showed a reduction of microglia in the hippocampus, especially in the dentate gyrus region, a
region inherently associated to neurogenesis. In addition, we found a reduction in doublecortin-positive neurons
in conditional Caspase-3 knockout mice, which corresponds to a reduction in neurogenic neurons. Furthermore,
using high-resolution image analysis, we also observed a reduction in the phagocytic capacity of microglia
lacking Caspase-3. Behavioral analysis using object recognition and Y-maze tests showed altered memory and
learning in the absence of Caspase-3. Finally, we identified specific microglia located specifically in neurogenic
niche positive for Galectin 3 which colocalized with Cleaved-Caspase-3 in control mice. Taken together, these
results showed the essential role of Caspase-3 in microglial function and highlight the relevant role of this
specific microglial phenotype in the maintenance of AHN in the hippocampus.
Abstract
Ministerio de Ciencia e Innovación de España y fondos Europeos FEDER/UE - PID2021-124096OB-I00Abstract
Junta de Andalucía de España y fondos europeos FEDER/EU - P18-RT-1372Abstract
Universidad de Sevilla - VI PPIT-USAdditional details
Identifiers
- URL
- https://idus.us.es/handle//11441/147438
- URN
- urn:oai:idus.us.es:11441/147438