All tags Neuroscience The functions of glia in the CNS

The functions of glia in the CNS

An overview of the roles and relationships of astrocytes, oligodendrocytes and microglia in the CNS.

Introduction

The central nervous system (CNS) comprises a network of approximately 1012 neurons, which mediate the transmission of action potentials. Despite the essential function of neurons, about 90% of the cells in the CNS are glia. Glia were originally believed to be passive cells that only acted physically to support neurons, hence the name glia meaning 'glue'.

However, it is now known that glia play an active role in many central homeostatic processes and also during development. Four main types of glia exist, namely astrocytes, oligodendrocytes, ependymal cells and microglia.

Further information on glia can be found in the related links or by viewing all neuroscience and glia resources.


Astrocytes

Astrocytes (Figure 1) provide a link between the vasculature and neurons transporting glucose and other substances out of the bloodstream (Tsacopoulos and Magistretti 1996; Magistretti and Pellerin 1999). Glucose is glycolytically processed by astrocytes to produce lactate, which is the main energy substrate used by neurons.

Astrocytes also play a role in the uptake of neurotransmitters such as glutamate and gamma-aminobutyric acid (GABA) (Kimelberg and Katz 1985; Kimelberg and Norenberg 1989; Schousboe et al., 2004) and the regulation of extracellular potassium ion concentration, both of which are functions that are crucial for the propagation of action potentials (Ransom and Sontheimer 1992; Newman and Reichenbach 1996).

"Astrocytes provide a link between the vasculature and neurons transporting glucose and other substances out of the bloodstream"

In addition, astrocytes perform immune functions (Fontana et al., 1984; Constantinescu et al., 2005; Alarcon et al., 2005; Hull et al., 2006), synthesize and release neurotrophic factors and are involved in the formation of neural scars following injury (Fawcett and Asher 1999; Silver and Miller 2004).

During development, radial glia - which differentiate into astrocytes when neuronal migration is complete - provide a supporting matrix for neuronal migration and synaptogenesis (Ransom and Sontheimer 1992; Chanas-Sacre et al., 2000; Mori et al., 2005).

​​

Figure 1: GFAP-positive astrocyte within a neuronal culture
Cultures of cerebellar granule neurons were stained after 7 days in culture with an antibody recognizing glial fibrillary acidic protein (GFAP) to identify astrocytes. Anti-GFAP was detected using anti-mouse IgG secondary antibody conjugated to biotin. The staining was subsequently visualized by incubating the cells with a pre-formed avidin-biotin horseradish peroxidase (HRP) complex for 1 hour at room temperature, followed by treatment with DAB. Cells were counterstained with hematoxylin to provide an estimation of total cell number and neurons were identified according to morphological criteria.


Oligodendrocytes

Oligodendrocytes comprise several short processes, which wrap themselves around neurons present in the CNS. Oligodendrocytes are responsible for axonal regulation and the generation and maintenance of the myelin sheath that surrounds axons. The main role of myelin is to mediate rapid saltatory propagation of action potential between Nodes of Ranvier, thereby facilitating neuro-transmission (Ransom and Sontheimer 1992; Edgar and Garbern 2004).

Oligodendrocytes also secrete a number of neurotrophins including nerve growth factor (NGF)brain derived neurotrophic factor (BDNF) and neurotrophin-3 (Dai et al., 2003), which provide local trophic support for neurons. Peripheral axons are myelinated by Schwann cells and these cells in contrast to oligodendrocytes facilitate neuronal regeneration following injury (Torigoe et al., 1996).


Ependymal cells

Ependymal cells line the ventricles and the central canal of the spinal cord (Del Bigio 1995). The functions of ependymal cells remain largely speculative. However, ependymal cells possess micro-villi, which beat in a coordinated manner; therefore these cells are believed to be involved in the directional movement of cerebral spinal fluid (CSF), disturbances of which lead to hydrocephaly.

The directional flow of CSF is thought to facilitate the transport of nutrients into the brain and the removal of toxic metabolites. Ependymal cells have also been suggested to serve as an axonal guidance system during early development.


Microglia

Microglia are the immune effector cells of the CNS and are present in abundance in the brain parenchyma. They constitute approximately 10-20% of the total population of glial cells in the adult (Vaughan and Peters 1974; Banati 2003). These cells are derived from blood-borne macrophages, which migrate into the CNS during development.

More detailed information on  microglia subtypes and markers can be found in our overview.

Microglia are small round cells that comprise numerous branching processes and possess little cytoplasm. Classically, microglia were considered to be inactive under physiological conditions, however, it is now known that microglia exhibit pinocytotic activity and localized motility (Booth and Thomas 1991; Glenn et al., 1991) particularly of their ramified protrusions (Nimmerjahn et al., 2005). Microglial processes directly contact neuronal cell bodies, astrocytes and blood vessels (Nimmerjahn et al., 2005).

"Microglia constitute approximately 10-20% of the total population of glia cells in the adult"

Therefore, it seems likely that microglia monitor the well-being of the brain and also function to cleanse the extracellular fluid in order to maintain central homeostasis (Booth and Thomas 1991; Thomas 1992; Fetler and Amigorena 2005). Furthermore, the presence of neurotransmitter receptors on microglia means that these cells can respond to released neurotransmitters (Boucsein et al., 2003; Light et al., 2006; Taylor et al., 2003,2005).

In response to injury or pathogen invasion microglia transform into active phagocytic macrophages in an attempt to combat disease (Kreutzberg 1996; Stence et al., 2001). Following a damaging event, reactive microglia accumulate at the site of injury (Giordana et al., 1994; Dihne et al., 2001; Eugenin et al., 2001) where they play a neuroprotective role phagocytosing damaged cells and debris. In acute lesions the peak of microglial activation occurs 2-3 days post insult, but if the pathological stimulus persists microglial activation continues (Banati 2003).

In addition to their roles in the adult, microglia play a pivotal role during development by removing inappropriate axons (Innocenti et al., 1983; Marin-Teva et al., 2004) and through the promotion of axonal migration and growth (Polazzi and Contestabile 2002).

For more detail on microglia, read our overview of microglia subtypes and markers.


​References

Written by C. Hooper and J.M. Pocock.

  • Alarcon R., Fuenzalida C., Santibanez M., von Bernhardi R. (2005) Expression of scavenger receptors in glial cells. Comparing the adhesion of astrocytes and microglia from neonatal rats to surface-bound beta-amyloid. J. Biol. Chem. 280, 30406-30415.
  • Banati R. (2003) Neuropathological imaging: in vivo detection of glial activation as a measure of disease and adaptive change in the brain. Brit. Med. Bul. 65, 121-131.
  • Booth P. L., Thomas W. E. (1991) Evidence for motility and pinocytosis in ramified microglia in tissue culture. Brain Res. 548, 163-171.
  • Boucsein C., Zacharias R, Farber K, Pavlovic S, Haqnisch U, Kettenmann H. (2003) Purinergic receptors on microglial cells: Functional expression in acute brain slices and modulation of microglial activation in vitro.  Euro. J. Neurosci. 17, 2267-2276.
  • Chanas-Sacre G., Rogister B., Moonen G., Leprince P. (2000) Radial glia phenotype: origin, regulation and transdifferentiation. J. Neurosci. Res. 61, 357-363.
  • Compson A., Zajicek J., Sussman J., Webb A., Hall G., Muir D., Shaw C., Wood A., Scolding N. (1997)  Glial lineages and myelination in the central nervous system. J. Anat. 190:161-200.
  • Constantinescu C. S., Tani M., Ransohoff R. M., Wysocka M., Hilliard B., Fujioka T., Murphy S., Tighe P. J., Sarma J. D., Trinchieri G., Rostami A. (2005) Astrocytes as antigen-presenting cells expression of IL-12/IL-23. J. Neurochem. 95, 331-340.
  • Dai X., Lercher L. D., Clinton P. M., Du Y., Livingston D. L., Viera C., Yang L., Shen M. M., Dreyfus C. F. (2003) The trophic role of oligodendrocytes in the basal forebrain. J. Neurosci. 23, 5846-5853.
  • Del Bigio M. (1995) The ependyma: a protective barrier between brain and cerebrospinal fluid. Glia. 14, 1-13.
  • Edgar J. M., Garbern J. (2004) The myelinated axon is dependent on the myelinating cell for support and maintenance: molecules involved. J. Neurosci. Res. 76, 593-598.
  • Eugenin E. A., Eckardt D., Theis M., Willecke K., Bennett M . V., Saez J. C. (2001) Microglia at brain stab wounds express connexin 43 and in vitro form functional gap junctions after treatment with interferon gamma and tumour necrosis factor alpha. Proc. Natl. Acad. Sci USA. 98, 4190-4195.
  • Fawcett J. W., Asher R. A. (1999) The glial scar ad central nervous system repair. Brain Res. Bull. 49, 377-391.
  • Fetler L., Amigorena S. (2005) Brain under surveillance the microglia patrol. Science. 309, 392-393.
  • Giordana M. T., Attanasio A., Cavalla P., Migheli A., Vigliani M. C., Schiffer D. (1994) Reactive cell proliferation  and microglia following injury to the rat brain. Neuropathol. Appl. Neurobiol. 20, 163-174.
  • Glenn J. A., Booth P. L., Thomas W. E. (1991) Pinocytic activity in ramified microglia. Neurosci. Lett. 123, 27-31.
  • Hull M., Muksch B., Akundi R. S., waschbisch A., Hoozemans J. J., Veerhuis R., Fiebich B. L. (2006) Amyloid beta peptide (25-35) activates protein kinase C leading to cyclooxygenase-2 induction and prostaglandin E (2) release in primary midbrain astrocytes. Neurochem Int. Epub ahead of print.
  • Innocenti G. M., Clarke S., Koppell H. (1983) Transitory macrophages in the white matter of the developing visual cortex. II. Development and relations with axonal pathways. Dev. Brain Res. 11, 55-66.
  • Kimelberg H. K., Katz D. M. (1985) High-affinity uptake of serotonin into immunocytochemically identified astrocytes. Science. 228, 889-891
  • Kimelberg H. K., Norenberg M. D. (1989) Astrocytes. Sci. Am. 260, 44-52.
  • Kreutzberg G. W. (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 19, 312-318.
  • Light A.R., Wu Y., Hughen R.W., Guthrie P.B. (2006) Purinergic receptors activating rapid intracellular Ca2+  increases in microglia. Neuron Glia Biology 2:125-128.
  • Magistretti P. J., Pellerin L. (1999) Astrocytes couple synaptic activity to glucose utilisation in the brain. News Physiol. Sci. 14, 177-182.
  • Marin-Teva J. L., Dusart I., Colin C., Gervais A., van Rooijen N., Mallat M. (2004) Microglia promote the death of developing purkinje cells. Neuron. 41, 535-547.
  • Mori T., Buffo A., Gotz M. (2005) The novel roles of glial cells revisited: the contribution of radial glia and astrocytes to neurogenesis. Curr. Top. Dev. Biol. 69, 67-99.
  • Newman E., Reichenbach A. (1996) The Muller cell: a functional element of the retina. Trends. Neurosci. 19, 307-312.
  • Nimmerjahn A., Kirchhoff F., Helmchen F. (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 308, 1314-1318.
  • Polazzi E., Contestabile A. (2004) Reciprocal interactions between microglia and neurons: from survival to neuropathology. Rev. Neurosci. 13, 221-242.
  • Ransom B. R., Sontheimer H. (1992) The neurophysiology of glial cells. J. Clin. Neurophysiol. 9, 224-251.
  • Schousboe A., Sarup A., Bak L. K., Waagepetersen H. S, Larsson O. M. (2004) Role of astrocytic transport processes in glutamatergic and GABAergic neurotransmission. Neurochem. Int. 45, 521-527.
  • Silver J., Miller J. H. (2004) Regeneration beyond the glial scar. Nat. Rev. Neurosci. 5, 146-156.
  • Stence N., Waite M., Dailey E. (2001) Dynamics of microglial-activation: a confocal time-lapse analysis in hippocampal slices. Glia. 33, 256-266.
  • Taylor DL, Diemel LT, Pocock JM (2003) Activation of microglial group III metabotropic glutamate receptors protects neurons against microglial neurotoxicity. J Neurosci 15:2150-2160.
  • Taylor DL, Jones F, Chen Seho Kubota ESF, Pocock JM (2005) Stimulation of microglial metabotopic glutamate receptor, mGlu2 triggers TNFα-induced neurotoxicity in concert with microglial derived FasL. J Neurosci 25:2952-2964.
  • Thomas W. E. (1992) Brain macrophages: evaluation of microglia and their functions. Brain Res. Rev. 17, 61-74.
  • Torigoe K., Tanaka H. F., Takahashi A., Awaya A., Hashimoto K. (1996) Basic behaviour of migratory schwann cells in peripheral nerve regeneration. Exp. Neurol. 137, 301-308.
  • Tsacopoulos M., Magistretti P. J. (1996) Metabolic coupling between glia and neurons. J. Neurosci. 16, 877-885.
  • Vaughan D. W., Peters A. (1974) Neuroglial cells in the cerebral cortex of rats from young adult to old age: an electron microscopy study. J. Neurocytol. 3, 405-429.

J.M. Pocock - Cell Signalling Laboratory, Department of Neuroinflammation, Institute of Neurology, University College London, 1 Wakefield Street, London, WC1N 1PJ.

Sign up