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Chapter 2

CHAPTER 2 – Neurons and Glia.docx

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Diane Mangalindan

CHAPTER 2 – Neurons and Glia  Neurons are the most important cells for the unique functions of the brain  It is the neurons that sense changes in the environment, communicate these changes to other neurons, and command the body’s responses to these sensations  Glia/ glial cells are thought to contribute to rain function mainly by insulating, supporting, and nourishing neiboring neurons The Neuron Doctrine  Neurons are 40-200 times smaller than most cells which range of 0.01- 0.05 mm in diameter  Progress in cellular neuroscience was not possible before the development of the compound microscope in the late seventeenth century  Brain tissue has a consistency of jello – thus, the study of the anatomy of brain cells had to await the development of a method to harden the tissue without disturbing its structure and an instrument that can product very thin slices th  Early in the 19 century scientists discovered how to fix tissues by immersing them in formaldehyde and developed a special device called a microtome to make very thin slices  These technical advances spawned the field of histology – the microscopic study of the structure of tissues  The final breakthrough in neurohistology was the introduction of stains that could selectively color some parts of the cells in brain tissue  Franz Nissl showed that a class of basic dyes would stain the nuclei of all cells and also stain clumps of material surrounding the nuclei of neurons  Clumps are called nissl bodies and the stain is known as the nissl stain  Nissl stain distinguishes neurons and glia from one another and enables histologists to study the arrangement or cytoarchitecture of neurons in different parts of the brain  The study of cytoarchitecture led to the realization that the brain consists of many specialized regions (each which performs a different function) The Golgi Stain  Camillo golgi discovered that by soaking brain tissue in silver chromate solution (now called golgi stain) a small percentage of neurons became darkly colored in their entirety  This revealed that the neuronal cell body that is shown with the nissl stain, is actually only a small fraction of the total structure of the neuron  The golgi stain shows that neurons have at least two distinguishable parts: a central region that contains the cell nucleus, and numerous thin tubes that radiate away from the central region  The region that contains the cell nucleus has several names : cell body, soma, perikaryon  The thin tubes that radiate away from the soma are called neurites and the two types are axons and dendrites  Cell body usually gives rise to a single axon which is uniform diameter throughout its length and has branches that extend at right angles  It was recognized by the histologists of the day that axons must act like ‘wires’ that carry the output of the neurons  Dendrites rarely extend more than 2mm in length  Histologists recognized that because dendrites come in contact with many axons, they must act as the antennae of the neuron to receive incoming signal Cajal’s Contribution  Santiago Ramon y Cajal used the golgi stain to work out the circuitry of many regions of the brain – although they both had two different views  Golgi championed the view that the neurites of different cells are fused together to form a continuous reticulum/network  Cajal argued that the neurites of different neurons are not continuous with one another and must communicate by contact, not continuity  The idea that the neuron adhered to the cell theory is known as the neuron doctrine  With the rise of the electron microscope, it was finally possible to show that the neurites of different neurons are not continuous with one another The Prototypical Neuron  The inside of the neuron is separated from the outside by the limiting skin, the neuronal membrane, which gives each part of the cell its special 3D appearance The Soma  The cell body of the typical neuron is about 20 micrometer in diameter  The watery fluid inside the cell (cytosol) is a salty, potassium-rich solution that is separated from the outside by the neuronal membrane  Within the soma are a # of membrane-enclosed structures called organelles  Cell body of the neuron contains the same organelles that are found in animal cells  The most important ones are the nucleus, the rough ER, the smoothe ER, the golgi, and the mitochondria 1. The Nucleus  Spherical, centrally located, about 5-10 micrometers across  Contained within a double membrane called nuclear envelope  Within it are chromosomes, which contain the genetic material, DNA  The DNA in each of your neurons is the same which is the same as the DNA in your liver  What distinguishes a neuron from a liver cell are the specific parts of the DNA that are used to assemble the cell which are segments of DNA called genes  Each chromosome contains an uninterrupted double-stranded brain of DNA (2nm wide)  The reading of the DNA is known as gene expression  The final product of gene expression is the synthesis of molecules called proteins  Protein synthesis – the assembly of protein moleculesm occurs in the cytoplasm (but DNA never leaves the nucleus)  Therefore, there is an intermediary that carries the genetic message to the sites of protein synthesis in the cytosol  This function is performed by mRNA  Process of assembling a piece of mRNA that contains the info of a gene is called transcription  Protein coding genes are flanked by stretches of DNA that are not used to encode proteins but are important for regulating transcription  At one end of the genes is the promoter – the regions where the RNAP binds to initiate transcription  Binding of RNAP to promoters is regulated by other proteins called transcription factors  At the other end is a sequence of DNA called the terminator that the RNAP recognizes as the end point for transcription  Introns – additional stretches od DNA within gene that cannot be used to code for protein  Coding sequences are called exons  Initial transcript has introns and exons but then by a process called RNA splicing, the introns are removed and the exons are fused  Sometimes, specific exons are also removed with introns – alternative splicing  This way, a single gene can ultimately give rise to several different mRNAs and polypeptides  Building blocks of proteins are amino acids (20 different kinds)  Assembling of proteins from amino acids under direction of mRNA = translation  Central dogma = DNA  mRNA  Protein (beings with DNA of the nucleus and ends with the synthesis of protein molecules)  Molecular neurobiology = information contained in the genes is used to determine the structure and functions of neuronal proteins 2. Rough ER  Enclosed stacks of membrane dotted with dense globular structures called ribosomes (25nm in diameter)  Rough ER abounds neurons far more than glia or most other non- neuronal cells  rough ER is known as another name : Nissl bodies (organelle stained with dyes  rought ER is a major site of protein synthesis in neurons  RNA transcripts bind to ribosomes on ER  Ribosomes take raw material in the form of amino acids and manufacture proteins using the blueprint provided by the mRNA  Many ribosomes are freely floating and are called free ribosomes  Several ribosomes may appear to be attached to a single strand of mRNA (polyribosomes), and the associated ribosomes are working on it to make multiple copies of the same protein 3. Smooth ER and Golgi Apparatus  Remainder of cytosol of the soma is crowded with stacks of membranous organelles (smooth ER)  Smooth ER is continuous with rough ER  Golgi = stack of membrane-enclosed disks in the soma that lies farthest from the nucleus  it is the site of extensive ‘post-translational’ chemical processing of proteins  one important function of golgi is the sorting of certain proteins that are destined for delivery to different parts of the neuron, such as the axon and dendrites 4. Mitochondrion  In neurons, these sausage shaped strucutres measure about 1 micrometer in length  Withint he enclosure of their outer membrane are multiple folds of inner membrane called cristae  Between cristae is an inner space called matrix  Mitochondria is site of cellular respiration  within the inner compartment of mitochondrion, pyruvic acid enters krebs cycle  biochemical products of the krebs cycle provide energy that, in another series of reactions within the cristae (ETC) results in the addition of phosphate to ADP = ATP (cells energy source)  17 ATP molecules are released for every molecule of pyruvic acid  chemical energy in ATP is used to fuel biochemical rxns of neuron The Neuronal Membrane  the neuronal membrane serves as a barrier to enclose the cytoplasm inside the neuron and to exclude certain substances that float in the fluid that bathes the neuron  an important characteristic of neurons is that the protein composition of the membrane varies depending on whether it is in the soma, the dendrites or the axon  the function of neurons cannot be understood without understanding the structure and function of the membrane and its associated proteins The Cytoskeleton  gives the neuron its characteristic shape  bones of the cytoskeleton are microtubules, microfilaments and neurofilaments 1. Microtubules  20nm in diameter  big and run longitudinally down neurites  appears as straight, thick-walled hollow pipe  wall of the pipe is composed of smaller strands and each of those strands consist of the protein tubulin  a strand consists of tubulins stuck together like pearls on a string  process of joining small proteins to form a long strand is called polymerization and a resulting strand is polymer  polymerization and depolymerization of MTs and therefore of neuronal shape can be regulated by various signals within the neuron  microtubule-associated protein (MAPs) participate in the regulation of MT assembly and function  MAPs anchor the MT to one another and to other parts of the neuron ALZHEIMER’S DISEASE AND THE NEURONAL CYTOSKELETON  Neurites elaborate branching patterns, critical for info processing, reflect the organization of the underlying cytoskeleton  Devastating loss of brain function can result when the cytoskeleton of neurons is disrupted  Alzheimers disease is characterized by the disruption of the cytoskeleton of neurons in the cerebral cortex, a region of the brain crucial for cognitive function  One of the first disease symptoms was a strong feeling of jealousy towards her husband  Soon she showed rapidly increasing memory impairments  Following her death, changes in the neurofibrils elements of the cytoskeleton that are stained by silver solution were noted  The bielschowsky silver preparation showed very characteristic changes in the neurofibrils  Inside an apparently normal-looking cell, one or more single fibers could be observed that became prominent through their striking thickness and specific impregnability  At a more advanced stage, many fibrils arranged parallel showed the same changes and then accumulated forming dense bundles and gradually advanced to the surface of the cell  Eventually, the nucleus and cytoplasm disappeared and only a tangled bundled of fibrils indicated the site where once the neuron had been located  As these fibrils can be stained with dyes different from the normal neurofibrils, a chemical transformation of the fibril substance must have taken place  This might
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