06-NSCI2101-- Cells-2024 (1).pdf

First Review Session Tuesday, September 16 4-5pm Room MCB 3-146 No new material Chance to ask questions and practice what you know  Cells Lecture 06 Maureen Riedl (she/her/hers) Department of Neuroscience University of Minnesota Remember - All Life is Made of Cel...

First Review Session Tuesday, September 16 4-5pm Room MCB 3-146 No new material Chance to ask questions and practice what you know  Cells Lecture 06 Maureen Riedl (she/her/hers) Department of Neuroscience University of Minnesota Remember - All Life is Made of Cells Cells use a complex set of chemical reactions (“metabolism”) to grow, reproduce, and continue living. Cells are surrounded by a cell membrane that isolates their chemical reactions from the outside world, to allow conditions for life to be maintained. Cells use some of their metabolic energy pumping ions (i.e. sodium, potassium, chloride) into or out of the cell. Remember - Cells are Different Different types of cells in nervous system Neurons Glia Different shapes of cells Small, medium or large Pyramidal, stellate, granular etc Different functions Send and receive electrical signals long distances Create a myelin sheath Support neurons Etc. One way to study cells - Microscopy Classic histological method Treat the tissue with a preservative (e.g. formaldehyde). Dissect the region of interest. Embed the tissue. Cut the tissue into thin sections. Stain the tissue to reveal subject of interest. Examine with a microscope. Microscopy - staining Different stains can be used to show different cell type, organelles or molecules. This purple stain shows This purple stain shows myelin, which is on axons. neuronal cell bodies. Microscopy – Conventional Compound Light low magnification high magnification  Microscopy - fluorescence Good for showing molecules in sample glial cell neuron  Microscopy - Electron Good for studying organelles Uses metals instead of dyes to stain Microscopy Magnification allows identification of more detail Neuron – Nerve cell Has organelles (like nucleus or mitochondria) just like many other types of cells in the body. Despite having the same organelles, neurons have unique functions Organelles of Cells – Cell Membrane Forms the external boundary of the cell body, axons, and dendrites. It is about 6-8 nanometers thick. Must remain intact for neurons to function properly Organelles – Cell Membrane Cell membrane is a phospholipid bilayer that forms an impenetrable barrier. Proteins are embedded in or attached to this bilayer. Receptors Ion channels and pumps More later Organelles - Nucleus Round structure usually in center of cell body. Often the most obvious organelle. * *Nucleus can also refer to a group of neurons in the brain or spinal cord that have similar properties. We’ll talk about that another day, but this is NOT that day.** Organelles - Nucleus Consists of Nuclear membrane or nuclear envelope – double layer with pores to allow diffusion of select molecules between nucleus and cytoplasm Chromasomes – double strands of DNA complexed with proteins Nucleolus – genesis of RNA and ribosomes  Medium magnification Organelle - Nucleus: light micrograph Electron micrograph Low magnification light micrograph 14 Nucleus - Genes and Protein Synthesis Humans have 23 pairs of chromosomes The 23rd pair are sex chromosomes XX - female XY - male Duplication or deletion of chromosome causes abnormalities Trisomy 21 (Down syndrome) results from extra copy of 21st chromosome Causes characteristic facial appearance Intellectual and physical challenges Varying levels of severity Nucleus – Genes and protein synthesis DNA & Genes DNA is a helical chain of four types of nucleotides in a specific sequence. Many segments of the DNA of a chromosome are genes. A gene encodes the instructions for synthesis of a protein. Humans have ~23,000 genes. Genes are the basis of heredity. Most cells of an individual have the same DNA (genes).  Nucleus – Genes and protein synthesis Protein synthesis: A gene is used as a template for synthesis of messenger RNA (mRNA) in the nucleus mRNA is used as a template for synthesis of a protein in the cytoplasm. DNA (gene) > mRNA > protein Different cell types express only certain proteins. The function of a cell is determined by the proteins it expresses.  Nucleus – Genes and protein synthesis DNA is a chain of four nucleotides. mRNA is a chain of four slightly different nucleotides. Protein is a chain of amino acids. The sequence of three nucleotides in the mRNA specifies the amino acid to assemble into the protein being synthesized. Thus, the sequence of nucleotides in a gene (DNA) ultimately determines the sequence of amino acids in a protein.  Nucleus – Genes and protein synthesis Protein synthesis: A gene is used as a template for synthesis of messenger RNA (mRNA) in the nucleus mRNA is used as a template for synthesis of a protein in the cytoplasm. DNA (gene) > mRNA > protein Different cell types express only certain proteins. The function of a cell is determined by the proteins it expresses. Most protein synthesis in a neuron occurs in the soma  Nucleus – Genes and protein synthesis Synthesis of mRNA from DNA in the nucleus is a process called transcription. Synthesis of protein from mRNA in the cytoplasm is a process called translation. Organelles - Ribosomes Ribosome reads the sequence of RNA to synthesize proteins Can be free in the cytoplasm Can be attached to endoplasmic reticulum Organelles – Endoplasmic Reticulum Net-like meshwork of a highly convoluted single membrane Extends throughout the cytoplasm When ribosomes are attached, called rough ER Rough ER is important for synthesis of membrane proteins and proteins for export Some smooth ER makes up Golgi apparatus  Organelles of Neurons– Rough ER – Nissl Substance Neurons have large amounts of rough endoplasmic reticulum in their somas, which we call Nissl substance. Nissl substance is readily seen by microscopy. Most proteins and other molecules needed by neurons are synthesized in the soma.  Organelles – Rough ER – Nissl substance Nissl stain: Low magnification light micrograph High magnification light micrograph of spinal cord of a spinal neuron Organelles – Golgi apparatus Aggregation of flat vesicles made up of smooth ER Vesicles that contain proteins bud off from rough ER and are transported to the Golgi apparatus Golgi Proteins in these vesicles are apparatus modified in the Golgi apparatus and packaged into vesicles. These vesicles are transported throughout the cell. Organelles - Mitochondria Composed of a double membrane Generate energy for the neuron Are present in soma, dendrites, and axons of cells Organelles - Lysosomes Membrane-bound vesicles Formed from Golgi apparatus Contain enzymes for breaking down organelles and molecules for recycling  Organelles - Cytoskeleton Filaments form a matrix in cytoplasm of cell. Main determinant of the shape of the cell Involved in cell movement Involved in transport of molecules and organelles throughout the cell. Three main elements: Microtubules (tubulin) - shape Intermediate filaments – neurofilament in neurons – support long processes Microfilaments (actin) – growth cones microtubules nucleus Generic Neuron - Axonal Transport Cell body (soma) Axon Dendrite Synapse Remember…. In neurons, most protein synthesis takes place in the cell body. Very little mRNA is present in the axon.  Axonal transport Yet most of the volume of a neuron can be in its axon. Axonal transport is required to move molecules and organelles around the cell. Organelles – Cytoskeleton – Axonal Transport The “cargo” in the anterograde direction is moved by “motors” called kinesins Anterograde The “cargo” in the retrograde direction is moved by “motors” called dyneins Retrograde Axonal Transport - Fast Can be anterograde or retrograde Fast anterograde transport 100-400mm/day Things needed at the axon terminal Retrograde Transport 50-200mm/day Materials from nerve terminals to cell body Nerve growth factors Stenoien DL, Brady ST. Discovery and Conceptual Development of Fast and Slow Axonal Transport. Available from: https://www.ncbi.nlm.nih.gov/books/NBK28078/ Axonal transport – Slow antergrade Slow anterograde transport 0.25-5mm/day Movement of mictrotubules and neurofilaments Stenoien DL, Brady ST. Discovery and Conceptual Development of Fast and Slow Axonal Transport. Available from: https://www.ncbi.nlm.nih.gov/books/NBK28078/ Axonal transport Rabies Introduced through skin, often from animal bite Virus is taken up by peripheral nerve terminals and transported retrogradely into cell bodies of the CNS. Once in the soma, it releases its mRNA and results in synthesis of viral proteins. These viral proteins damage the host neuron causing the production and release of even more viruses. Axonal transport Herpes simplex Type I – causes cold sores Type II – gentital herpes (STD) Easily transmitted between partners It is transported in sensory neurons and will survive in the soma of sensory neurons for life. Glia or Neuroglia Non-neuronal cells of the nervous system CNS glia: Astrocytes – support the neurons Oligodendrocytes – myelinate axons Ependymal cells – line the ventricular system Microglia – housekeepers PNS glia: Satellite cells – support the neurons Schwann cells – myelinate axons Macrophages – housekeepers Non-neuronal cells – CNS - Astrocytes Star shaped glial cells of CNS Most abundant cell type of the brain and spinal cord Surround most neurons and blood vessels Contribute to the cellular scaffolding of the CNS Non-neuronal cells – CNS – Astrocytes - Mediate exchange between capillaries and neurons; contribute to the blood brain barrier Non-neuronal cells – CNS - Astrocytes They remove and recycle neurotransmitter. They ‘insulate’ synapses from one another. They regulate the extracellular ionic environment of the neurons. Non-neuronal cells – CNS - Oligodendroglia Cell bodies wrap around axon Increase conduction velocity (more later) Non-neuronal cells – CNS - Microglia Regulate brain development Maintain neuronal networks Become activated by injury