Glial contributions to neuronal health and disease: new insights from Drosophila

Abstract

Glial cells are essential for proper formation and maintenance of the nervous system. During development, glia keep neuronal cell numbers in check and ensure that mature neural circuits are appropriately sculpted by engulfing superfluous cells and projections. In the adult brain, glial cells offer metabolic sustenance and provide critical immune support in the face of acute and chronic challenges. Dysfunctional glial immune activity is believed to contribute to age-related cognitive decline, as well as neurodegenerative disease risk, but we still know surprisingly little about the specific molecular pathways that govern glia-neuron communication in the healthy or diseased brain. Drosophila offers a versatile in vivo model to explore the conserved molecular underpinnings of glial cell biology and glial cell contributions to brain function, health, and disease susceptibility. This review addresses recent findings describing how Drosophila glial cells influence neuronal activity in the adult fly brain to support optimal brain function and, importantly, highlights new insights into specific glial defects that may contribute to neuronal demise.

Figure 1. Glial subtypes in the adult Drosophila CNS

Schematic diagram of the adult fly brain illustrates representative classes of glia. In the cortical regions of the CNS, cortex glia (magenta) surround neuronal cell bodies, likely providing important metabolic and functional support. Neuropil areas of the central brain, which house axonal and dendritic projections, contain two major glial subtypes: Ensheathing glia (light green) enwrap neuronal extensions and appear to serve as the primary immune responders in adult animals, while astrocytes (red) modulate synaptic signaling. Representative diagrams of ensheathing glia and astrocytes within the antennal lobe neuropil (ALN) are shown. The entire nervous system is covered by a double layer of surface glial cells (blue outline), which offers a protective barrier between the CNS and the circulating hemolyph. A more recently identified cohort of glial cells in the adult retina (R), Semper cells (dark green), regulate photoreceptor function in a manner comparable to mammalian Mueller glia.