Mitochondrial calcium uniporter deficiency in dentate granule cells remodels neuronal metabolism and impairs reversal learning.

ABSTRACT: The mitochondrial calcium uniporter (MCU) is the main route of calcium (Ca²⁺) entry into neuronal mitochondria. This channel has been linked to mitochondrial Ca²⁺ overload and cell death under neurotoxic conditions, but its physiologic roles for normal brain function remain poorly understood. Despite high expression of MCU in excitatory hippocampal neurons, it is unknown whether this channel is required for learning and memory. Here, we genetically down-regulated the Mcu gene in dentate granule cells (DGCs) of the hippocampus and found that this manipulation increases the overall respiratory activity of mitochondrial complexes I and II, augmenting the generation of reactive oxygen species in the context of impaired electron transport chain. The metabolic remodeling of

SUBMITTER: Rose HM 

PROVIDER: S-EPMC10770303 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature