Microglia, resident immune cells of the brain, react to the presence of pathogens/danger signals with a large repertoire of functional responses including morphological changes, proliferation, chemotaxis, production/release of cytokines, and phagocytosis. In vitro studies suggest that many of these effector functions are Ca2+-dependent, but our knowledge about in vivo Ca2+ signalling in microglia is rudimentary.
Throughout the lifespan, microglia, the primary innate immune cells of the brain, fulfill a plethora of homeostatic as well as active immune defense functions, and their aging-induced dysfunctionality is now considered as a key trigger of aging-related brain disorders.
Neuronal hyperactivity is the emerging functional hallmark of Alzheimer’s disease (AD) in both humans and different mouse models, mediating an impairment of memory and cognition. The mechanisms underlying neuronal hyperactivity remain, however, elusive.
Brains’ high energy expenditure with preferable utilization of glucose and ketone bodies, defines the specific features of its energy homeostasis. The extensive oxidative metabolism is accompanied by a concomitant generation of high amounts of reactive oxygen, nitrogen, and carbonyl species, which will be here collectively referred to as RONCS.
Functioning at the interface between the nervous and immune systems, in the amyloid-depositing brain, astrocytes become hypertrophic and accumulate around senile plaques. Moreover, hippocampal astrocytes upregulate their γ-aminobutyric acid (GABA) content and enhance tonic inhibition, likely causing local circuit imbalance.