11.09.10-Cell biology of the Nervous system.txt

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11.09.10-Cell biology of the Nervous system.txt
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  1. The Neuron
    • Functional unit of the nervous
    • system
    • Function is to receive and integrate informationTo conduct this
    • information to other regions of the NS, and then to transmit this
    • information to other neurons and cells
  2. Functions of a Nervous System
    • Receive information from environment outside and inside the bodyProcess,
    • integrate and interpret this information to organize motor responses
    • appropriate for survival; provide the ability to change
    • (learning/plasticity)The CNS contains nerve cells, glial cells,
    • fibroblasts, and macrophages
  3. 11.09.10-Cell biology of the Nervous system
    • Understand the function of the nervous system
    • Describe the morphological features of nerve cells and their functions
    • Describe the differences between unipolar, pseudounipolar, bipolar, multipolar neurons
    • Understand the concepts of axonal transport and myelination and their importance
    • Describe the types and functions of glial cells in the PNS and CNS. Describe the anatomical and physiologica/biochemical properties of the BBB
  4. Dendrites
    • Specialized to veceive information from other nerve cells
    • Contain receptors for neurotransmitters released by other neurons
    • The diversity of neuron shape is due to the complexity of dendrites: number of dendrites and their degree of branching depend on the typ of nerve cell and its task in integrating signals from other neurons.
  5. Dendrites contain dendritic spines, their function is
    • Sites for synapse
    • Increase the surface area for synapses and
    • Compartmentalize synaptic activity: because they are separated from the main dendrite – each synapse can change independently of others
  6. Dendrites contain ribosomes
    • Their action is to be actively involved in protein synthesis
    • Allows LOCAL CONTROL of the structure and physiology of the synapses
  7. Cell Body
    • Contains: nucleus, cytoplasm (contains ribosomes), ER, Golgi, mitochondria, lysosomes, etc.
    • May contain pigment: lipofuscin granules; melanin
    • Has a major role in protein synthesis for sustaining the dendrites, axon and terminals
  8. Rough ER/ribosomes in the cell body
    • Appear as clumps (Nissl Substance) when stained.
    • Related to abundant synthesis of proteins destined for membrane insertion or export
    • Dispersion of Nissl substance = chromatolysis
  9. Axon: conducts action potentials
    • Single axon emerges from the axon hillock: this is where APs are initiated
    • May have branches
    • Vary in length 10 um – 1 m!
    • Most axons are covered by a myelin sheath
  10. Myelin formed by
    • CNS: oligodendrocytes
    • PNS: Schwann cells
  11. Myelin: functions
    • acts as an electrical insulator along axon and supports the axon nutritionally
    • increases the conduction speed for action potentials and it is crucial for propagation of APs along its entre length
    • Myelin sheath is interrupted at regular intervals where one glial cell ends and another begins: Nodes of Ranvier
    • Ion channels are concentrated at the nodes: where APs occur
  12. Myelin – diseases
    • Viral genetic, autoimmune, etc: peripheral neuropathy, multiple sclerosis
    • Degradation of myelin – and impaired propagation of action potentials – impaired function
    • Myelin = glial cell membrane: lipid bilayer has higher proportions of sphingomyelin and glycosphingolipids compared to other cell membranes
  13. Sphingomyelin is synthesized from
    • Ceramide (FA-sphingosine) + phosphatidylcholine = sphingomyelin
    • By sphingomyelin synthase
    • Degraded by sphingomyelinase
  14. Glycosphingolipids: cerebrosides, gangliosides, sulfatides
    • Ceramide + saccharide
    • Degraded by hydrolases
  15. Implications of myelin biochemistry for disease:
    • 1. Degradation of sphingomyelin and glycosphingolipids require specific enzymes: genetic defects in these enzymes cause developmental storage diseases (sphingolipidoses)
    • 2. Myelin proteins are susceptible to viral, genetic, immunologic disorders that cause demyelination
    • 3. Saccharide components of glycosphingolipids make them ANTIGENIC: ! they are involved in autoimmune responses that cause peripheral demyelination
  16. Symaptic terminal
    Two types of synapses exist: electrical synapse (gap junction) and chemical synapse
  17. Electrical synapse (gap junction)
    • Two neurons are physically connected through membrane channels (gap junctions) formed by proteins called connexins
    • Allows electrical current to flow between two neurons: BIDIRECTIONALLY
    • Though not most common synapses, known to be expressed throughout the CNS: cortex, thalamus, hippocampus, cerebellum, retina, and between glia
  18. Chemical synapse
    • Most common type of synapse
    • Two neurons are separated by a 20 nm cleft; presynaptic terminal releases neurotransmitter contained in vesicles that binds to receptors on post synaptic neuron. Neurotransmitters excite or inhibit postsynaptic neurons, depending on the properties of the receptors
  19. Postsynaptic locations for synapses
    • Usually on dendrites
    • BUT can also occur on cell bodies and axons
    • Dendrites usually densely populated with synapses from other neurons: each neuron typically receives 100s-1000s of synapses
  20. Why do synapses exist?
    • Can integrate signals, a modulate synaptic transmission
    • Have remarkable property of changeability: PLASTICITY
    • The amount of transmitter released or the properties of the postsynaptic receptors can change depending upon previous activity – learning! And memory!
  21. Cytoskeletal components support neuronal structure
    • Actin
    • Microtubules
    • Intermediate filaments
    • Account for difference in neuronal morphology, defects impair neuronal function! Can lengthen and shorten dynamically to allow changes in cell shape
  22. Actin filaments
    • Anchor transmembrane molecules
    • Keep ion channels/receptors in place
  23. Microtubules
    • Support the tubular structure of axons and mediate axonal transport
    • MTs provide a pathway for moving components a lot more quickly than diffusion
    • Energy-requiring axonal transport
  24. Axonal transport
    • depends upon motor proteins (kinesin, dynein) up to 100 mm/day
    • is bidirectional
    • can sort proteins to specific locations!: NT receptors to dendrites; proteins involved in NT release to terminals
    • Axonal transport requires energy to move cargo: so when metabolically impaired – impaired transmission – tends to be worst for neurons with the longest axons – peripheral neuropathy: !
  25. Intermediate filaments
    Regulate axon diameter
  26. Defects in cytoskeletal components assembly or of related proteins are involved in disease
    • MT defects – affect nuclear migration during cortical development: lissencephaly
    • Several neurodegenerative diseases (Alzheimer’s; Parkinsons): are associated with MT-associated proteins (tau, alpha-synuclein)
  27. Toxins that depolimerize microbutules
    • Vincristin
    • Colchicines
  28. Toxins that depolimerize intermediate filaments
    Acrylamide
  29. Toxins that depolimerize actin filaments
    Cytochalasin
  30. Unipolar neurons
    One process connected to cell body: NOT present in vertebrates!
  31. Pseudounipolar neurons
    • One process connected to cell body
    • Called pseudo because initially 2 processes that fuse into one
    • MOST peripheral sensory neurons are pseudounipolar
  32. Bipolar neurons
    • Two processes connected to cell body
    • 1 axon and 1 dendrite
  33. Multipolar
    • One axon but multiple dendrites
    • Most CNS neurons are multipolar! : multiple dendrites give this neuron the greatest ability to integrate information
  34. Functional classifications of neurons
    • Sensory
    • Motor
    • Interneurons
    • Projection neurons
    • The simplest vertebrate pathway contains a chain of 2 neurons: sensory neuron connected to a motor neuron. Most pathways contain a chain of 3 or more neurons – provides opportunity for increased integration of information and interaction between neurons – capacity for more complex responses and detection of finer features of stimuli
    • Excitation and inhibition can be combined in many ways to control activity
  35. Glial Cells
    • The “other” cells of the NS
    • Support neuronal structure, metabolism, growth/repair, and response to injury
    • Actively communicate with neurons and participate in nerve cell function
  36. PNS Glia
    • Schwann cells, satellite cells
    • 1. Peripheral nerves are supported by connective tissue (fibrolasts, collagen, macrophages)
    • 2. Schwann (satellite) cells surround cell bodies in ganglia
    • 3. schwann cells surround axons where they may be myelinating or nonmyelinating; they also surround neuromuscular junctions
    • Schwann cells release frowth factors that ingluence recovery from injury:!
  37. CNS Glia
    • Oligodendrocytes, astrocytes, microglia, ependyma
    • CNS lacks fibroblasts and connective tissue
    • Astrocytes!
  38. Astrocytes
    • Protoplasmic: found in gray matter
    • Fibrous: found in white matter
    • Radial glia guide neuron migration during development
    • Long processes: that give the cell appearance of a star; some processes terminate as end feet on capillaries, nodes of Ranvier, and synapses
    • Astrocyte end feet on capillaries – basal lamina connected and makes the BBB
    • Contain and intermediate filament protein known as Glial Fibrillary Acidic Protein (GFAP): used to identify astrocytes in pathological conditions
  39. Functions of Astrocytes
    • End-feet provide communication route between extracellular space and blood
    • Remove excess K+ from the extracellular space
    • Ensheath CNS synapses and remove neurotransmitters from extracellular space
    • Proliferate in response to injury (reactive gliosis)
    • Secrete growth factors and extracellular matrix
    • Guide neuronal migration in embryo; may provide neuronal stem cells in adult
    • Participate in neuronal metabolism: metabolize glucose to lactate and provide the lactate to neurons as an energy source
  40. Blood Brain Barrier
    Many molecules, including small ions, water soluble molecules, charged molecules, many proteins, most nonessential amino acids and nonessential fatty acids cannot enter the CNS from blood vessels
  41. Blood Brain Barrier – components
    • Capillary endothelial cells held together by adhesive junctions (adherens junctions and tight “occludens junctions)
    • Basal lamina
    • astrocyte end feet – presumed to induce impermeable tight junctions btw endothelial cells of brain capillaries
    • Body capillaries – partial barrier to large molecules
    • Brain capillaries block diffusion of almost all molecules
  42. Additional structural, physiological and biochemical properties that strengthen the BBB:
    • 1. additional layers separate blood from neurons: capillaries are covered by a basement membrane containing collagen fibers that are densely covered by astrocyte endfeet
    • 2. No fenestrated endothelium in brain capillaries: in body, not in brain
    • 3. No pinocytosis at the luminal surface: prevents uptake of macromolecules from the blood into endothelial cells
    • 4. Increased enzymatic activity: in brain endothelial cells, aids metabolism of neuroactive blood-borne molecules and drugs. ATP-dependent efflux transporters remove molecules that enter endothelial cells
    • 5. Endothelial membrane it polarized: along the luminal/ablumenal axis to provide an active mechanism for maintaining brain homeostasis
  43. What substances CAN enter the brain from blood
    • Lipid-soluble molecules such as alcohol (those that can pass through lipid bilayers
    • Glucose and amino acids for which darrier-mediated transporters are present
  44. Circumventricular organs are regions in the CNS that have not BBB
    • Located near the midline adjacent to the 3rd and 4th ventricles
    • Important sites of communication with blood:
    • posterior pituitary and median eminence of hypothalamus: for release of hormones
    • area postrema of medulla: monitors blood toxins and controls vomiting
    • areas around 3rd ventricle: monitor blood osmolarity and gut hormones
  45. Bad thing about BBB
    • Much decreased immune response
    • Few white cells
    • Little complement
    • Decreased immunoglobulins

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