Preventing neurodegeneration by adrenergic astroglial excitation

Abstract

Impairment of the main noradrenergic nucleus of the human brain, the locus coeruleus (LC), which has been discovered in 1784, represents one of defining factors of neurodegenerative diseases progression. Projections of LC neurons release noradrenaline/norepinephrine (NA), which stimulates astrocytes, homeostatic neuroglial cells enriched with adrenergic receptors. There is a direct correlation between the reduction in noradrenergic innervations and cognitive decline associated with ageing and neurodegenerative diseases. It is, therefore, hypothesized that the resilience of LC neurons to degeneration influences the neural reserve that in turn determines cognitive decline. Deficits in the noradrenergic innervation of the brain might be reversed or restrained by increasing the activity of existing LC neurons, transplanting noradrenergic neurons, and/or using drugs that mimic the activity of NA on astroglia. Here, these strategies are discussed with the aim to understand how astrocytes integrate neuronal network activity in the brain information processing in health and disease.