MATILDA
Financiado
Microglia As conTroller of braIn metaboLism During Aging
Microglia represent the main brain residential immune cells. In the last years evidence emerged that, besides representing the first line of defense against pathogenic insults, microglia are also centrally involved in physiologic...
Microglia represent the main brain residential immune cells. In the last years evidence emerged that, besides representing the first line of defense against pathogenic insults, microglia are also centrally involved in physiological functions essential for correct CNS development and function. Microglia, in a spatially and temporally controlled manner, influence neuronal apoptosis, neurogenesis and myelin formation and manage synapse homeostasis, including removing supernumerary synapses during development. These widely heterogeneous roles are supported by distinct subtypes -or states- of microglia, present in different regions of the brain and at different times during CNS development. In the last years, Triggering Receptor Expressed on Myeloid cells 2 (Trem2) emerged as a key gene which controls the microglial metabolic state, in addition to directing synapse elimination and shaping the functional brain connectivity. In the present project, I propose that microglia, via Trem2, direct the genetic signature of specific subgroups of brain cells, shifting them toward specific metabolic and developmental patterns. I hypothesize that this mechanism is key for the control of metabolism in the hypothalamus, where the neuronal contingents orchestrating systemic energy homeostasis reside. By using a combination of transcriptomics, multiplex protein expression analysis and cell-based imaging methods, I will determine which subsets of microglia cooperate within hypothalamic centers and will define the underlying mechanisms. I will also assess whether defects in this orchestrated crosstalk affect the central regulation of energy and glucose homeostasis during aging. Data from this study will provide comprehensive knowledge of microglia functions in shaping hypothalamic complexity and endocrine output. Also, they will offer a targeting potential for new therapeutic strategies that could reverse immunometabolic dysfunction by modulation of hypothalamic microglial function.
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Duración del proyecto: 65 meses
Fecha Inicio: 2022-07-25
Fecha Fin: 2027-12-31
Fecha Fin: 2027-12-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-07-25
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2021-ADG:
ERC ADVANCED GRANTS
Cerrada
hace 3 años
Presupuesto
El presupuesto total del proyecto asciende a
3M€
Líder del proyecto
HUMANITAS MIRASOLE SPA
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5