Artículo
Microglial Caspase-3 is essential for modulating hippocampal neurogenesis.
Autor/es | Alonso Bellido, Isabel María
Posada Pérez, Mercedes Hernández Rasco, Francisco Vázquez Reyes, Sandra Cabanillas, María Herrera Carmona, Antonio José Soldán Hidalgo, Jesús Espinosa Oliva, Ana María Martínez de Pablos, Rocío Venero Recio, José Luis Ruiz Laza, Rocío |
Departamento | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
Fecha de publicación | 2023 |
Fecha de depósito | 2023-06-23 |
Publicado en |
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Premios | Premio Anual Publicación Científica Destacada de la US. Facultad de Farmacia |
Resumen | 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 ... 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. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) Junta de Andalucía Universidad de Sevilla |
Identificador del proyecto | PID2021-124096OB-I00
P18-RT-1372 VI PPIT-US |
Cita | Alonso Bellido, I.M., Posada Pérez, M., Hernández Rasco, F., Vázquez Reyes, S., Cabanillas, M., Herrera Carmona, A.J.,...,Ruiz Laza, R. (2023). Microglial Caspase-3 is essential for modulating hippocampal neurogenesis.. Brain, Behavior, and Immunity, 112, 206-219. https://doi.org/10.1016/j.bbi.2023.06.013. |
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