Cells in focus
Glial cells more than support cells?

https://doi.org/10.1016/j.biocel.2006.10.022Get rights and content

Abstract

Glial cells are the most abundant cells in the human brain and have long been considered as passive supporting cells for neurons. In contrast to the extensive studies on various neuronal functions in the nervous system, we still have limited knowledge about glial cells. Recently a number of pioneering studies have provided convincing evidence that glia play active roles in development and function of the central nervous system. This review discusses recent advances in our understanding of the molecular mechanisms underlying glial cell differentiation. We then highlight some of the novel findings about glial function, i.e. the role of glia in synaptogenesis and the intricate relationship between astrocytes and adult neural stem cells. Finally, we summarize the emerging studies that implicate abnormalities in the formation or maintenance of glia leading to severe brain diseases, such as Alexander disease, glioblastoma and multiple sclerosis, and potential therapeutic strategies to tackle these diseases.

Introduction

The nervous system is composed of two major cell types: neurons and glia. Strikingly, glial cells constitute 90% of cells in the human brain. The name of glia originates from Greek for glue, but now we know glia do not just hold nerve cells together and thus should not just be considered as supportive cells to neurons in the nervous system. Instead, recent compelling studies indicate that glial cells play more active and essential roles in brain development and brain function than previously acknowledged (Allen & Barres, 2005; Doetsch, 2003, Haydon, 2001; Seifert, Schilling, & Steinhauser, 2006).

There are three types of glial cells in the central nervous system (CNS): astrocytes, oligodendrocytes and microglia. Astrocytes are the most abundant glial cells with irregular star-shaped cell bodies and broad end-feet on their processes. They interact extensively with neurons and provide them with important structural and metabolic support. Oligodendrocytes have relatively small amounts of cytoplasm around the nucleus but have several processes which wrap themselves around axons to form myelin sheaths. Microglia are the smallest of the glial cells which act as phagocytes, the immune cells of the CNS, to clean up debris.

Section snippets

Cell origin and plasticity

The mammalian cerebral cortex originates from a single layer of proliferating neuroepithelial cells. These neural progenitor cells (NPC, a subpopulation of which is also referred to as neural stem cells, NSC) line the ventricles, forming the ventricular zone (VZ). NPCs in the VZ proliferate and sequentially give rise to three major cell types of the brain: neurons, astrocytes, and oligodendrocytes (Sauvageot & Stiles, 2002; Sun, Martinowich, & Ge, 2003). Unlike astrocytes and oligodendrocytes,

Functions

One of the well-known functions of glial cells is to help form an impermeable lining in the brain's capillaries and venules, the blood-brain barrier, that prevents toxic substances in the blood from entering the brain. In addition, glia control the levels of neurotransmitters such as glutamate and dopamine. For example, astrocytes facilitate rapid removal of synaptic glutamate following its release from the presynaptic terminal, thus prevent glutamate-mediated neurotoxicity which can induce

Associated pathologies

Astrocytes underlie the pathological states of reactive gliosis and glial scar formation accompanying nerve injury (Sofroniew, 2005). Gliosis and neuronal loss in certain brain regions are seen in a variety of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Amyotrophic lateral sclerosis (ALS) (Boillee, Vande Velde, & Cleveland, 2006). Microglia are believed to be responsible for producing neuroinflammation in these conditions (Hoozemans, Veerhuis, Rozemuller, &

Acknowledgements

We thank Dr. Volkan Coskun and Ryan Schmidt (University of California, Los Angeles) for critical reading of the manuscript and members of the Sun laboratory for helpful discussions. We apologize for our inability to include and discuss all the studies in this area within the limitations of this article. FH was supported by UCLA Dissertation Year Fellowship. This work is supported by NIH RO1 grant MH066196 and NIH project grant HD006576.

Cited by (87)

  • Unraveling unique and common cell type-specific mechanisms in glioblastoma multiforme

    2022, Computational and Structural Biotechnology Journal
    Citation Excerpt :

    Oligodendrocytes are further classified into oligodendrocyte precursor cells (OPCs), premyelinating or newly formed oligodendrocytes (NFOs) and myelinating oligodendrocytes (MOs) based on their degree of differentiation [10,11]. Microglial cells are the smallest, most eminent immune cells of the CNS that remove debris and account for around 10% of the whole brain cell population [8,12,13]. They are the first responders when improper events occur in the brain [12].

  • Sphingosine 1-phosphate – A double edged sword in the brain

    2017, Biochimica et Biophysica Acta - Biomembranes
    Citation Excerpt :

    Considering the close association between S1P-signalling, inflammation and autophagy, it would be interesting to study the S1P-inflammation- autophagy axis in the brain. Astrocytes constitute the majority of glial cell populations in the central nervous system (CNS) and are involved in brain homeostasis and in maintaining synaptic functions [77] Their function in the CNS is quite complex and casually inconsistent [55]. Astrocytes become activated in response to many CNS pathologies and are involved in immune responses [78].

View all citing articles on Scopus
View full text