Principal Investigator: Francesco Moccia

The neurovascular unit is a functional structure comprising neurons, astrocytes, endothelial cells and pericytes and responsible for adjusting local cerebral blood flow (CBF) to the metabolic demands of firing neurons. Neurons may control vascular reactivity by either releasing vasoactive compounds, such as nitric oxide (NO) and prostaglandin E2 (PGE2), or stimulating adjoining astrocytes to release vasoactive arachidonic acid metabolites. Curiously, it is still unclear whether brain microvascular endothelial cells play any role in translating neuronal activity into vasoactive signals. Recent work from our group showed that acetylcholine directly triggers NO release from mouse brain microvascular endothelial cells by promoting repetitive oscillations in intracellular Ca²⁺ concentration, which in turn recruit the endothelial NO synthase (eNOS). The present projects aims at assessing whether glutamate and acetylcholine, two major brain neurotransmitters, stimulate intracellular Ca²⁺ signals and NO release in human brain microvascular endothelial cells (hCMEC/D3). We will use a multidisciplinary approach consisting of molecular (RT-PCR and immunoblotting) and imaging techniques to investigate the Ca²⁺ toolkit available to hCMEC/D3 cells to generate Ca²⁺ signals and activate Ca²⁺-dependent decoders, such as eNOS. Furthermore, we will assess whether and how exposure to b-amyloid peptide alters the Ca²⁺ machinery and NO release in hCMEC/D3 cells. Our results will shed novel light on the cellular and molecular underpinnings of blood oxygen level dependent (BOLD) signals both in health and disease.

Recent Publications:

• Iadecola C (2004). Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci, 5(5):347-60
• Mapelli L, Gagliano G, Soda T, Laforenza U, Moccia F, D’Angelo EU (2016). Granular layer neurons control cerebellar neurovascular coupling through an NMDA Receptor/NO-dependent system. J Neurosci, 37(5):1340-1351.
• Zuccolo E, Lim D, Kheder DA, Perna A, Catarsi P, Botta L, Rosti V, Riboni L, Sancini G, Tanzi F, D’Angelo E, Guerra G, Moccia F (2017). Acetylcholine induces intracellular Ca2+ oscillations and nitric oxide release in mouse brain endothelial cells. Cell Calcium 66:33-47