Unveiling the Interplay: Neurovascular Coupling, Astrocytes and G Protein-Coupled Receptors in Alzheimer's Disease

Astrocytes are a type of glial cell that are involved in actively modulating synaptic plasticity, neurotransmitter homeostasis, and neuroinflammatory responses. More importantly, they coordinate neuronal activity and cerebral blood flow (CBF) in what is known as neurovascular coupling (NVC). NVC is an essential mechanism that maintains the high energy demand the brain requires by supplying continuous and rapid supply of oxygen and nutrients through CBF. Impairment in NVC is one of the key events that triggers a spiral of occurrences that lead to the clinical advancement of Alzheimer's disease (AD). It is yet to be determined what the molecular manifestations of NVC impairment relate to; nonetheless, it is believed that alterations in G protein-coupled receptors (GPCRs) are responsible for exacerbating these effects. In this review, we summarize the current evidence supporting the involvement of GPCRs on astrocytes in NVC and the pathophysiology of AD. Additionally, we propose potential research directions to further elucidate the underlying mechanisms and evaluate the feasibility of targeting specific GPCRs as a therapeutic strategy to correct brain blood flow and memory impairments associated with AD.