Neurogliovascular alterations in brain pathologies across lifespan

Neurological and psychiatric illnesses present significant challenges across different stages of life. Adolescence is associated with a high incidence of eating disorders along with mood and anxiety disorders, while aging frequently brings psychiatric conditions that precede or accompany neurodegenerative diseases. Current treatments targeting neurotransmitter systems have limited effectiveness, with high relapse rates and few options to slow down disease progression. Increasing evidence highlights the importance of glial cells and the neurogliovascular unit (NVU) in brain pathologies. The NVU is formed by endothelial cells, pericytes, astrocytes, microglia, and neurons. Among many functions, it modulates cerebral blood flow and supports blood-brain barrier (BBB) integrity while being involved in neuroinflammatory responses. High peripheral inflammation in eating disorders could lead to BBB disruption and pro-inflammatory astrocytic and microglial states, affecting neuronal health and subsequently promoting unhealthy eating habits. Endothelial and glia cells play a central role in mood and anxiety disorder pathophysiology by fostering brain inflammation via BBB leakage and NVU alterations. In neurodegenerative conditions, such as Alzheimer’s and Parkinson’s diseases, NVU dysfunction aggravates cognitive decline and neuronal loss, while also contributing to amyloid-β and α-synuclein aggregation. This review seeks to highlight current knowledge about the involvement of the NVU in brain disorders across lifespan, stressing the need to better integrate vascular and glial research in targeted therapeutic strategies to optimize symptom alleviation, slow down or even prevent eating, mood, anxiety and neurodegenerative conditions. • Increased inflammation contributes to vascular dysfunction in brain pathologies. • The neurogliovascular unit may participate in eating disorders. • Mood disorders are associated with impaired endothelial and glial cell functions. • Neurogliovascular alterations are found in neurodegenerative diseases. • Research on sex differences in brain pathologies is limited at the vascular level.