Astrocytes

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Science

Astrocytes are the most abundant cell type in the human brain1,2. While these cells were first identified in 1860 by Otto Deiters3, the primary focus of neuroscience research for the past century and a half has been on the neurons that transmit electrical currents throughout the body, essentially providing the wiring for thoughts, memories and motor function. The importance of astrocytes and other glia cells are only now being fully investigated and appreciated for their multifunctional role, including their critical roles in the maintenance and repair of the brain after injury.

The human brain utilizes tremendous amounts of energy – despite being only 2% of the body’s weight, the brain receives 15% of the cardiac output, 20% of total body oxygen consumption, and 25% of total body glucose utilization4. To help fuel the brain, astrocytes are well known to provide trophic support to neurons and other brain cells. Maintaining the proper ion concentrations across nerve membranes, so they are ready to transmit electrical signals or action potentials, is by far, the primary energy dependent need of neurons. Astrocytes also utilize both glycolysis and oxidative phosphorylation to generate considerable levels of ATP for their own needs. They help to maintain ion homeostasis, support neurons and are thought to be an integral component in both the maintenance and signaling of the chemical synapse.

The morphology of astrocytes is well designed to enable these caretaker functions. As the name implies, astrocytes are star-shaped cells with many protrusions that branch out and form non-overlapping networks throughout the brain. Each astrocyte will touch many epithelial cells on arteries, neurons, other astrocytes, and other glia cells. It is estimated that a single astrocyte can contact ~100,000 synapses in the hippocampus and ~300-600 dendrites in the cortex5,6. The animated image below is of actual human brain tissue with astrocytes having been stained with a green fluorescent marker and neurons with a red fluorescent marker; note how the neuron is surrounded by astrocytes, and will have multiple connections to various astrocytic processes. Given the remarkable cellular networking, astrocytes provide crucial support and signaling from multiple arteries to many neurons in a region.

Our understanding of astrocyte functions continues to grow. In addition to the well-established roles of trophic support and ion homeostasis, astrocytes are now recognized to organize the structural architecture of the brain including regulation and maintenance of the blood brain barrier. Both under normal conditions and during stress, astrocyte functions range from providing substrates for neuronal metabolism, to clearing away neurotransmitters after signaling, to providing neurons with antioxidant substrates. Astrocytes also modulate neuronal plasticity and are critical for proper synapse formation between neurons, leading to the recent rewrite of scientific textbooks to describe the tripartite synapse7. Furthermore, it has also now been firmly established that astrocytes conduct intracellular and intercellular signaling cascades through excitable calcium waves, which parallels the classic electrical waves utilized by neurons, simply at slower propagation speeds. These localized or large global calcium waves can be initiated by various extracellular signals, including neurotransmitters. Taken together, all of the functions and signaling mechanisms attributed to astrocytes continues to rapidly progress, and consequently, its fundamental role as a brain caretaker cell positions it to be an exciting and relatively new therapeutic target.

Sources:

  1. Cherniak, C. The bounded brain: toward quantitative neuroanatomy. J Cogn Neurosci 2, 58-68 (1990).
  2. Nedergaard, M., Ransom, B. & Goldman, S.A. New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci 26, 523-30 (2003).
  3. Verkhratsky, A, Butt, A. “Introduction to Glia.” Glial Neurobiology: A Textbook. John Wiley & Sons, Ltd. (2007).
  4. Clark, DD. et al. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. Philadelphia: Lippincott; pp. 637–670. (1999).
  5. Bushong EA, et al. “Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains.” J Neurosci; 22:183–192. (2002).
  6. Halassa MM, et al. “Synaptic islands defined by the territory of a single astrocyte.” J Neurosci; 27:6473–6477. (2007).
  7. Araque, Alfonso et al. “Tripartite synapses: glia, the unacknowledged partner.” Trends in Neurosciences; Volume 22 , Issue 5 , 208 – 215 (1999).