The Other Brain by R. Douglas Fields, PhD
This book gave me a lot of insight into the importance and role of white matter in the brain.
I have written summaries of a few chapters below.
Part 1: Discovering The Other Brain
This part of the book is an introduction into glial cells, their types, and their discovery. First, Dr. Douglas Fields starts off by talking about the discovery of Camillo Golgi and what led Santiago Ramon y Cajal to draw pictures of neurons the way he did. Camillo Golgi discovered a technique, by accident, that allowed him to see the cell bodies of each neuron. However, it was Ramon y Cajal who was able to see that each one of the neurons were separate entities, drawing gaps, synaptic clefts, between each neuron. He also came up with the neuron doctrine. Ramon y Cajal was the first to recognize glial cells. Whenever he drew a collection of neurons, he would always leave spaces in between them. These spaces are where the glial cells belonged. Ramon y Cajal drew these cells separately showing their lack of axons or dendrites. Others saw there star like shape and they were then called, astrocytes.
We also learn that when trying to figure out why how Albert Einstein’s brain was different, the only difference that could be found was the increased number of astrocytes in his brain. The Rest of this section is just giving us an introduction into this “Other Brain”. Here is a compilation of my notes…
There are 4 major types of Glia
1. Astrocytes: Astrocytes provide energy source for neurons, lactate, Contain the protein filamentous, In diseased brains, such as in MS, filamentous appears in greater abundance in astrocytes, Now known as Glial Fibrillary Acidic Protein (GFAP) now known as the cellular skeleton of astrocytes p37, Not in the PNS, Get rid of potassium ions by sucking them into their cytoplasm
2. Microglia: smallest, most dynamic glia, the brain's defense against microorganisms, can transform from a latent multibranched solitary cell to an amoeboid cell, rush to kill invaders, Dr. Alois Alzheimer studied the cells as they were plentiful around senile plaques in brain tissue, They track down bacterium, cellular debris, or viruses and devour them, Attack using chemical release agents, neurotransmitter, glutamate, cytokines, reactive oxygen, nitrogen species, Collateral damage caused by glia is the source of many neurological disorders p44, can strip synapse connections from neurons
3. Oligodendrocytes: means stubby dendrite, Pondered by Ramon y Cajal’s student Pio del Rio-Hortega, found in the Central Nervous System, CNS, A single cell can wrap about 1um of myelin around 50 axons, destruction of myelin can cause MS, as electricity can “leak out” of an axon, Defective communication between neurons
4. Schwann (3 Types): Form myelin, named after Theodore Schwann;
Non-myelinating Schwann Cells: Small- diameter axons are not studded with Schwann cells, instead, they are cabled together by huge globular cells grasping bunches of them p31
Myelinating Schwann Cells
Terminal Schwann Cells
wrap around 1 cell
found in the Peripheral Nervous System, PNS
In the chapter, Transmissions from the Other Brain: Glia Know and Control Your Mind, we find out that “astrocytes not only respond to visual stimulation, they participate in vision by controlling neurons”. Richard Organs, John Nicholls, and Stephen Kuffler performed a study where they shined a light on a fish’s retina. They found that when they flashed the light, the voltage “suddenly dropped” inside of the astrocyte. These astrocytes of the optic nerve responded positively to potassium ions released from nerve axons when light hit the retina p49. This is because when the nerves are stimulated, they release potassium ions. Astrocytes absorb potassium ions, which makes the voltage inside of them more positive. Dr. Fields then reveals that calcium ions are the means by which information about the world is transmitted across cells and into their cytoplasm p53. This is the primary way the cells relay information.
Part 2: Glia in Health and Disease
Microglia and astrocytes both watch for bacteria and viruses causing infection in the brain.
On going controversial research: Using embryonic stem cells to help relieve human suffering from neurological diseases p65
Chapter 4 Brain Cancer: Almost Nothing to Do with Neurons
First we learn that mature neurons don’t become cancerous because they cannot divide/ undergo cell division.
SIDE NOTE, MY OPINION: On page 70, Dr. Fields writes that one doctor called out “Six weeks after I see patients with glioblastoma multiforme, they are dead! What more can I do?” I just read a post that talks about Non-invasive Tumor Treatment Fields, TTF, by Novocure. (Which is FDA approved!) It is a new, innovative type of treatment for glioblastoma. It is a device that the patients wears on their head that has the electric field producing transducer electrodes. The electrical fields interact with “key molecules” during mitosis that prevent the cells from undergoing cell division, or from properly undergoing cell division. Since the cell is not able to divide, it initiates a process called apoptosis, or programed cell death. At the moment, the technology is only used for solid tumors. inks for learning a bit more about the technology are below.
Link: <a href="http://www.novocure.com/our-therapy.aspx"><span class="s2">http://www.novocure.com/our-therapy.aspx</span></a></span>
TED: Bill Doyle, Engineer<span class="Apple-converted-space"> </span><a href="https://www.ted.com/talks/bill_doyle_treating_cancer_with_electric_fields?language=en">
We also learn that not all brain tumors are deadly, and that many are curable. In the section, Types of Tumors, we learn that all tumors in the brain arise from glial cells, although in rare occasions, neurons can become cancerous. Tumors from the PNS can be derived from Schwann cells. All it takes is for these cells to start abnormally dividing, giving rise to cancer.
Brain Cancer Type:
Glioblastoma: of brain cancers can be of egg shape can cross the Corpus Callosum
3:2 Male:Female
can cause necrosis and hemorrhages as they grow
Astrocytoma:
a brain cancers size of an apple
whitish in color
can grow diffusely p74
Pilocytic Astrocytoma:
found in the brainstem or cerebellum
most frequent tumor of the cerebellum and optic chiasm in children and adolescence
hair-like wavy fibrous appearance
Neuroblastoma:
of neuronal origin
arise from first 3 years of life
rarely in adults
Oligodendroglioma:
ages 35 - 40yrs
predominately in males
egg sized
usually develops in the frontal and temporal lobes
develop liquified cysts in white matter
can cause the surface of the cortex to grow abnormally p75
Glia have all of the ion channels that neurons have, including, potassium, chloride, sodium, etc. We learn that the tough part about cancerous cells is that they can spread. To facilitate migration, many cancer cells exude enzymes that dissolve the extracellular matrix that binds cells together p77. Dr. Harald Sontheimer of the University of Alabama at Birmingham hypothesized that the spaces between the cells are tight, which means that the cell has to shrink in order to get between them. He believed that these cells may be squeezing out the water of their cytoplasm in order to decrease its’ body mass, which meant that their ion channels are critical. We learn that salt causes bloating in cells and that in order to regulate their water concentration, they need to regulate the amount of salts coming through there ion channels, in particular, chloride. Dr. Herald Sontheimer’s group found that if they used chloride blockers, the cancerous cells could no longer migrate. In his groups tests, the glioma cells were not able to eliminate the contents of there ion channels, and thus, were not able to shrink. Drugs, such as chlorotoxin, which is extracted from the venom of scorpions, and is a chloride ion channel blocker, has been isolated. We learn that microglia are extremely attracted to glioma and astrocytoma, and some cases account for up to 70% of the cells in the tumor. Researchers are now targeting microglia to exploit there affinity to tumor cells. They are trying to use gene therapy, in order to use microglia as a cellular transport vehicle to deliver lethal genes to the tumor.
Names:
Dr. Herald Sontheimer, Dr. Helmut Kettenmann
Chapter 5 Brain and Spinal Cord Injury
Dr. R. Douglas Fields begins this chapter by talking about a cure for paralysis. In doing so he explains the glial and other cellular response that occurs upon spinal cord injury. Microglia transform from their resting stage to an amoeboid activated stage, rushing, alongside T- cells, the the area of injury. Both of these cells release reactive oxygen and other toxic chemicals which are designed to fight infection. Only, they are also very harmful to healthy cells. Astrocytes also rush the area of injury and transform to their reactive stage, releasing toxic materials and cytokines, which induce an inflammatory response. At this point oligodendrocytes and neurons are dying. These cells are dying, not only because of the initial injury, but because the neurotransmitter glutamate is being spilled over them in record amounts. Astrocytes then build “a robust cellular skeleton” called GFAP, a filamentous protein. This causes the impenetrable barrier, preventing other cells from entering. Next the astrocytes coat the barrier with chondroid sulfate glycan, which is a slippery substance. The microglia that are inside the barrier devour all of the cellular debris for which, later, after there are no more astrocytes in the area, all that is left is a fluid- filled cyst.
FACTS: Neurons begin to die right after there is injury to their axons. They activate their self destruct gene. However, some neurons do not activate their self destruct genes. This is because during regeneration, microglia and astrocytes release neurotropic factors that sustain the neuron p85. Astrocytes also secrete angiogenic factor which are proteins that stimulate new blood vessels to provide an infusion of vital food and oxygen to the damaged tissue p85.
Section: the cause and cure for paralysis
Studies:
Dr. Albert J. Aquayo and colleagues from McGill University in Montreal, Canada
Dr. Martin Schwab reasoned that if lack of NGF, nerve growth factor, was failing to sustain axon, then adding NGF would stimulate regeneration of severed axons. In his study using both CNS and PNS nerve tissue, his hypothesis was disproved. He found that the neurons grew well through the sciatic nerves, but not at all through the optic nerves.
Dr. Aquayo’s research involved grafting nerve segments into various regions of the spinal cord and brains of animals.
FUN FACTS: Vertebrates form myelin, invertebrates do not p38. Not all axons are myelinated p41.Glia can alter neuronal information at the synapse. Glia do not generate electrical impulses. They are sensitive to ion flux and have sensors to detect large numbers of neuronal signals, including neurotransmitter. After damage to the Blood Brain Barrier, immune cells can cross it, and damage the brain, turning into microglia. Schwann cells can build protein scaffolds called an extracellular matrix. A touch of a single finger of a growth cone on one of the proteins, haprin sulfate proteoglycan, can cause it, a cone, to collapse.
VOCABULARY
Dorsal Root Ganglion: Cells that carry the sensations of touch, heat, and pain from the skin to our spine p12.
Grey Matter
White Matter: Axons and glial cells
GBM: Glioblastoma Multiforme