11.09.10-Cell biology of the Nervous system.txt

• 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

• 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

• 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

• 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.

• 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

• Their action is to be actively involved in protein synthesis
• Allows LOCAL CONTROL of the structure and physiology of the synapses

• 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

• Appear as clumps (Nissl Substance) when stained.
• Related to abundant synthesis of proteins destined for membrane insertion or export
• Dispersion of Nissl substance = chromatolysis

• 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

• CNS: oligodendrocytes
• PNS: Schwann cells

• 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

• 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

• Ceramide (FA-sphingosine) + phosphatidylcholine = sphingomyelin
• By sphingomyelin synthase
• Degraded by sphingomyelinase

• Ceramide + saccharide
• Degraded by hydrolases

• 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

Two types of synapses exist: electrical synapse (gap junction) and chemical synapse

• 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

• 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

• 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

• 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!

• 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

• Anchor transmembrane molecules
• Keep ion channels/receptors in place

• 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

• 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: !

Regulate axon diameter

• MT defects – affect nuclear migration during cortical development: lissencephaly
• Several neurodegenerative diseases (Alzheimer’s; Parkinsons): are associated with MT-associated proteins (tau, alpha-synuclein)

• Vincristin
• Colchicines

Acrylamide

Cytochalasin

One process connected to cell body: NOT present in vertebrates!

• One process connected to cell body
• Called pseudo because initially 2 processes that fuse into one
• MOST peripheral sensory neurons are pseudounipolar

• Two processes connected to cell body
• 1 axon and 1 dendrite

• One axon but multiple dendrites
• Most CNS neurons are multipolar! : multiple dendrites give this neuron the greatest ability to integrate information

• 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

• 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

• 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:!

• Oligodendrocytes, astrocytes, microglia, ependyma
• CNS lacks fibroblasts and connective tissue
• 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

• 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

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

• 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

• 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

• Lipid-soluble molecules such as alcohol (those that can pass through lipid bilayers
• Glucose and amino acids for which darrier-mediated transporters are present

• 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

• Much decreased immune response
• Few white cells
• Little complement
• Decreased immunoglobulins