Historically, neuroscience has mainly focused on neuronal cell (dys)function. However, in past years it has become increasingly clear that glial cells, particularly astrocytes, play a key role in higher brain functions. In addition, recent studies show that astrocytic dysfunction is a central aspect in many different neurological conditions (e.g., ALS, Alzheimer’s and Huntington’s disease), neuropsychiatric disorders (schizophrenia, depression), and addictive disorders. Therefore, understanding how astrocytes help shape the brain, through specific interactions with other cell types, is an urgent challenge.

The main aim of SUPERGLUE (How SUbcellular ComPartments in AstroGlia control cognitive processing) is to identify the molecular mechanisms in astrocytes that control the formation, function and interplay of astrocyte endfeet and perisynaptic astrocyte processes (PAPs). These subcompartments enable astrocytes to exert their crucial function in higher brain function

 

SUPERGLUE, a consortium subsidized by the Dutch Research Council (NWO) XL program, brings together leading experts on astrocyte-vasculature interactions and those on astrocyte-synapse interactions. By joining forces at the VU Amsterdam, Amsterdam UMC and international partners, our consortium, led by Mark Verheijen (MCN/CNCR, VU Amsterdam) and Rogier Min (AUMC), has unique complementary expertise on required state-of-the-art techniques, instruments and innovative model systems to break new ground. This powerful and complementary combination of expertise and skills will enable unique insights into the molecular organization of astrocytes, in particular the dynamically regulated PAP and endfoot proteome. This will be used to guide functional experiments aimed at testing current hypotheses on the role of astrocytes and their specific subcompartments in optimizing cognitive brain function.

RESEARCH
Astrocytes have a complex morphology, forming two types of specialized structures (subcellular compartments): astrocyte endfeet that fully enwrap blood vessels in the brain, and perisynaptic astrocyte processes (PAPs) that surround the contact points that neurons use to communicate (synapses). This places astrocytes in a unique position, potentially enabling them to act as a bridge between respectively regulation of brain metabolism and fluid homeostasis on the one hand, and control over neuronal signal transmission on the other. However, insight into the establishment and dynamic regulation of these specific structures and the astrocyte bridge function, and how it is involved in cognitive processing is lacking.
By bringing together leading experts om astrocyte-vasculature interactions and astrocyte-synapse interactions, allied with unique technical expertise on state-of-the-art techniques present in the host labs, SUPERGLUE aims to take a leading step to unravel how astrocytes optimize brain functioning.

WP1: Map the dynamic proteome of astrocyte subcompartments

Researchers: Mark Verheijen, Priyanka Rao-Ruiz, Blanca Díaz-Castro
Goal: Identification of differences and similarities between PAP and endfoot proteomes, and how are these modulated by brain activity.

WP2: Identify proteins controlling formation and modification of astrocyte subcompartments (in vitro)
Researchers: Elga de Vries, Harold MacGillavry, Christian Henneberger, Rogier Min,
Goal: Address the role of key proteins in the formation and dynamic modification of astrocyte subcompartments, and how interfering with their function impacts these processes.

WP3: Determine the impact of interfering with astrocyte subcompartments on brain and behaviour (in vivo)
Researchers: Rogier Min, Erik Bakker, Mark Verheijen
Goal: Investigate how selected candidates orchestrate structural and functional alterations of astrocyte subcompartments in vivo, and how this impacts brain function.

WP4: Translation to the human brain
Researchers: Natalia Goriounova, Henner Koch
Goal: Confirm whether the mechanisms that control astrocytic PAPs and endfeet properties identified in mouse translate to humans.