The Other Brain

The Other Brain: From Dementia to Schizophrenia, How New Discoveries about the Brain Are Revolutionizing Medicine and Science by R. Douglas Fields, Simon & Schuster, 2009. 

Neurons and Glia

The cells that carry electrical impulses are called neurons. Neurons are unidirectional: they receive impulses on their dendrites and transmit nerve impulses along their axons. The axons are much longer than the dendrites. Glial (meaning glue) cells are cells in nervous tissue, such as the brain, spinal cord and peripheral nerves, that do not carry nerve impulses. Glia make up 85% of brain cells. Until recently, glia were thought to provide only biological support (oxygen, nutrition, immune response) to neurons. More recent studies have shown that they are also involved in regulating the structure and behavior of neurons. Neurons are fast, glia are slow.

Brain cancer is almost always caused by out-of-control division of glial cells, rather than neurons, because glia cells still divide, while neurons cannot. Neurons are unable to reproduce once they become strung-out. That is, they cannot undergo mitosis after they send out their long axons. 

Schwann Cells

Schwann cells are a kind of glia found in the peripheral nervous system. Each Schwann cell wraps around the axon of a particular neuron in the peripheral nervous system. The fatty cell membranes of the Schwann cells are an electrical insulator. This fatty insulation slows down the dissipation of the electrical charge of the nerve impulse and therefore speeds up the impulse. Axons are myelinated, but dendrites are not. Myelination occurs after neurons form synapses. Myelination is mostly completed by late adolescence. Invertebrates do not have myelin, so their nerve impulses travel more slowly. The earliest vertebrates, jawless fish such as lampreys and hagfish, do not have myelin, but higher vertebrates do.

Oligodendrocytes

Oligodendrocytes sheath axons in the central nervous system (brain and spinal chord). Unlike a Schwann cell, which will wrap only a single neuron, a single oligodendrocyte cell will wrap axons from many different neurons. This is how myelination differs between the central nervous system and the peripheral nervous system. Axons release ATP when they fire, and myelinating glia detect it. Babies who suffer oxygen deprivation during birth develop periventricular leukomalacia (PVL), the loss of oligodendrocytes. Alcohol during pregnancy kills the fetal brain cells that would otherwise differentiate into oligodendrocytes. Multiple sclerosis is an autoimmune disease where the immune system mistakenly targets the oligodendrocytes.

Astrocytes

Astrocytes regulate the number of synapses and their strength in the CNS. Schwann cells perform a similar function for the synapses between neurons and muscle cells. Astrocytes absorb excess potassium ions. Astrocytes are connected to each other by gap junctions which allow the flow of ions from one cell into another. Astrocytes have glutamate vesicles scattered throughout their cell body, and they release glutamate in response to calcium ions. Glial-derived neurotrophic factor (GDNF) is produced by astrocytes and has shown to help preserve the lives of the dopamine-producing neurons in the substantia nigra that die in Parkinson’s patients.

Oxytocin

A kind of neurosecretory cell in the hypothalamus called the magnocellular neuron produces the peptide hormone oxytocin and releases it into the bloodstream. Oxytocin manages smooth-muscle contraction during labor and lactation. Astrocyte glial cells regulate these oxytocin-producing neurosecretory cells.

Microglia

Microglia are the immune cells of the brain. They are needed because the white blood cells in the bloodstream cannot cross the blood-brain barrier. Microglia help repair damaged neurons. Fractalkine is a cytokine which damaged neurons release and which attracts microglia cells that help heal the injury.

Radial Glia

While the baby is in the womb, the radial glia provide a scaffolding for infant neurons to crawl up on. Each radial glial cell extends from the base of the brain to the top of the brain. Some of these radial glial cells later transform into astrocytes.

NG2 cells are a recently discovered type of glial cell. NG2 cells have stem-cell properties, can differentiate into neurons, and resemble immature oligodendrocytes. NG2 glia divide after stroke and brain injury.

Growth Cones

Axons have a growth cone that helps them repair broken connections. But this growth cone will collapse in the presence of several inhibitory proteins: myelin-associated glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), and the Nogo protein.  Researchers are trying to find drugs that will bind and inhibit these proteins, so that severed nerves can repair themselves. Fish and salamanders do not have the Nogo protein, but frogs do.

Pain and Cannabis

Glia are not involved in normal pain, but are involved in chronic pain. This involvement appears to be mediated by the cytokines that microglia release. Some glia have opiate receptors and cannabinoid receptors. There are two kinds of cannabinoid CB1 and CB2, and each kind of cannabinoid has a specific receptor. Neurons have CB1 receptors, but not CB2. The binding of CB1 to neurons is what makes CB1 psychoactive. Microglia have CB2 receptors. Experiments on mice have shown that CB2 can relieve pain without the psychoactive effects of CB1.