Histology of the CNS.pptx including neurons

cns hitology

1. CNS Histology

2. Neurons and glial cells The composition and function of different components of the neuron (e.g., plasma membrane, cell body, nucleus, nucleolus, cytoplasm, dendrites, and axon). List the different glial cells and their functions, and identify them on light and electron micrographs Different types of neurons found within the nervous system. Different types of neuroglia and their functions. The types of neuronal damage and the process of regeneration. <number>

3. Central Nervous System Peripheral Nervous System Structurally into: Neuron : functional unit of the nervous system. Neurons: Dendrites, cell body (the nucleus), axon, axon terminal. Synapses between neurons, generation of Post synaptic potentials, action potentials and propagation of action potentials along the axon. Neuroglia nonconducting cells that are located close to the neurons. They are referred to as neuroglial cells or simply glia . Types of glial cells: oligodendrocytes, astrocytes, microglia, and ependymal cells. <number> THE NERVOUS SYSTEM IS DIVIDED IN :

4. <number> Neurons communicate via synaptic transmission via neurotransmitters Dendrites: receive information → towards cell body Axons: carry information away from cell body Presynaptic terminal → postsynaptic terminal Neurons Axon Hillock

5. Neurons are also commonly classified into three major functional groups: sensory, motor, and interneurons. Sensory neurons carry information from the body's periphery into the nervous system → perception and motor coordination. Motor neurons carry commands from the brain → Motor neurons in spinal cord → Skeletal muscles. Interneurons constitute by far the largest class, consisting of all nerve cells that are not specifically sensory or motor, Interneurons are subdivided into two classes: Relay or projection interneurons have long axons and convey signals over considerable distances, from one brain region to another. Local interneurons have short axons and process information within local circuits.

6. Classification of Neurons

7. Unipolar neurons have a single primary process, that gives rise to many branches. One branch serves as the axon; other branches function as dendritic receiving structures. Bipolar neurons have an oval-shaped soma that gives rise to two processes: a dendrite that conveys information from the periphery of the body, and an axon that carries information toward the central nervous system. Many sensory cells are bipolar cells, including those in the retina of the eye and in the olfactory epithelium of the nose. Pseudo- unipolar cells: The mechanoreceptors that convey touch, pressure, and pain to the spinal cord . Multipolar neurons predominate in the nervous system of vertebrates. They have a single axon and, typically, many dendrites emerging from various points around the cell body. Multipolar cells vary greatly in shape .

8. <number> Other types of neurons Long axons Form the tracts of the CNS Intrinsic neurons (Golgi type II) Short axons Interneurons: inhibitory in nature Found in cerebral/cerebellar cortex Basket cells are multipolar GABAergic interneurons that function to make inhibitory synapses and control the overall potentials of target cells.

9. Examples of various types of neurons of multipolar cells from the cerebellar cortex ( A ) and from the cerebral cortex ( B and C ). Compare these with a pseudounipolar cell of the posterior root ganglion ( D ) and with bipolar cells from the retina ( E ) and olfactory epithelium ( F ). The Cell Biology of Neurons and Glia Fundamental Neuroscience for Basic and Clinical Applications Mihailoff, G.A.; Haines, D.E. © 2018.

10. A typical neuron has four morphologically defined regions: the cell body, dendrites, the axon, and presynaptic terminals The cell body (soma) metabolic center of the cell, contains the nucleus, the endoplasmic reticulum (REr). The cell body usually gives rise to two kinds of processes: several short dendrites and one tubular axon. Dendrites branch out in tree-like fashion receiv e incoming signals from other nerve cells. The axon propagation of electrical signals along distances ranging from 0.1 mm to 3 m. Action potentials: are rapid, transient, all-or-none nerve impulses, with an amplitude of 100 mV and a duration of about 1 ms. Action potentials are initiated at a specialized trigger region at the origin of the axon called the Axon Hillock (or initial segment of the axon).

11. <number> Plasma membrane: lipid bilayer; permits ion exchange via channels Cell body: nutrition center Nucleus: Double layered membrane with pores DNA Nucleolus (ribosome/rRNA production) Nucleoplasm Nissl bodies various-sized clumps of rough endoplasmic reticulum are prominent in the cytoplasm of neurons. Cellular Components of a Neuron

12. Mitochondria: energy center Golgi Apparatus: packaging center Lysosomes: contain hydrolytic enzymes Cytoskeleton Microtubules: (25-28 nm, 13 protofilaments, α / β) Neurofilaments: (10 nm); 2 protofilaments  protofibrils  neurofilaments; becomes tangled in Alzheimer’s Microfilaments (3 -7 nm); 2 actin strands in helix <number> Cellular Components of a Neuron

13. The cytoskeleton of the neuron consists of microfilaments, neurofilaments, and microtubules. Neurofilaments provide structural support for the neuron and are most numer­ous in the axon and the proximal parts of dendrites. Microfilaments form a matrix near the periphery of the neuron, forms structural specializations at synaptic mem­branes.

14. Elements of dendrite structure. Dendritic tree of a multipolar neuron ( A ) and dendritic spines ( B ), both in Golgi-stained cortical tissue. Ultrastructural features of dendrites, showing an axonal terminal bouton synapsing on a dendritic spine ( C ), a cross section of a dendrite with characteristic cytoskeletal elements and organelles ( D ), and a longitudinal section of a dendrite in the anterior horn of the spinal cord ( E ). MIT, mitochondrion; rER, rough endoplasmic reticulum. The Cell Biology of Neurons and Glia Fundamental Neuroscience for Basic and Clinical Applications Mihailoff, G.A.; Haines, D.E. © 2018

15. The cell body of a multipolar neuron as seen on electron micrograph and in a Golgi-stained preparation ( inset ). rER, rough endoplasmic reticulum. The Cell Biology of Neurons and Glia Fundamental Neuroscience for Basic and Clinical Applications Mihailoff, G.A.; Haines, D.E. © 2018

16. Elements of axon structure. Ultrastructural features of a small myelinated axon in a cross section of a peripheral nerve ( A ) and a longitudinal view at a node of Ranvier of a myelinated axon in the central nervous system ( B ). Drawing of the complete terminal arbor of an axon in the thalamus reconstructed from serial sections ( C ). The Cell Biology of Neurons and Glia Fundamental Neuroscience for Basic and Clinical Applications Mihailoff, G.A.; Haines, D.E. © 2018

17. Microtubules

18. ( t T Greek) Function: stabilizes microtubules Not present in dendrites Usually very soluble Misfolding  forms insoluble aggregates as seen in Alzheimer’s disease and Parkinson’s disease <number>

19. Microtubules are found in all parts of the neuron, and are the cytoplas­mic organelles used in axonal transport. Microtubules and Neuronal Degenerative Diseases In degenerative neuronal diseases of the CNS, a tau protein becomes excessively phosphorylated, which prevents crosslinking of microtubules. The affected microtubules form helical filaments , neurofibrillary tangles and senile plaques in the cell body and dendrites of neurons. Neurofibrillary tangles are prominent features of degenerating neurons in Alzheimer's disease, Amyotrophic Lateral Sclerosis, Down Syndrome patients.

20. Axons Dendrites Function Transport impulses receive impulses and transport them to the cell body Length Vary from microns to meters microns seldom more than a mm Branching pattern Limited to collaterals, preterminal and terminals from simple to complex arborizations Surface Smooth Varies from smooth to spiny Membrane supporting cells and myelin always naked

21. Axolemma (plasma membrane) Axoplasm (cytoplasm) Action potentials generate at axon hillock to transfer information Myelinated vs non- Myelinated <number>

22. Direction of Transport Speed of transport Proposed mechanism Substance carried Anterograde Forward flow of information: cell body to the terminal Fast (100-400 mm/day) Kinesin, microtubules Neurotransmitters in vesicles, mitochondria Proteins in vesicles Neurotransmitter-related cytosolic enzymes Glycoproteins Slow (∼1 mm/day) Movement neurofilaments and microtubules Cytoskeletal protein components (actin, myosin, tubulin and Calmodulin) Retrograde From nerve terminal to cell body Fast (50-250 mm/day) Dynein, microtubules Macromolecules in vesicles, Pinocytotic vesicles from axon terminal Axonal Transport

23. Fast retrograde transport: 50-200 mm/day from nerve terminal to cell body Transports: Nerve growth factor Herpes simplex virus Polio virus Rabies virus Tetanus toxin <number> Tetanus toxin binds to polysialogangliosides receptors present on motor nerve terminals which results in toxin internalization. Following internalization, tetanus toxin gets transported in a retrograde way from the peripheral nervous system to the central nervous system by retrograde axonal transport. When tetanus toxin reaches inhibitory neuron terminals , it prevents the presynaptic release of inhibitory neurotransmitters glycine and gamma-aminobutyric acid (GABA).

24. <number> Supporting Cells- Neuroglial cells: Microglia and Macroglia. Neuroglia are the structural supporting cells of the CNS More numerous than neurons Maintain environment for neurons to function appropriately. separate and insulate neuronal groups and synaptic connections from each other. Glial cells promote efficient signaling between neurons the blood-brain barrier—that prevents toxic substances in the blood from entering the brain. Two types of glial cells (oligodendrocytes and Schwann cells) produce the myelin Other glial cells apparently release growth factors

25. Three basic types of supporting or glial cells exist: - Ependymal cells line the fluid-filled cavities or ventricles of the brain and the central canal of the spinal cord. - Microglial cells are mesodermal in origin being derived from bone marrow, are formed in all parts of the brain and spinal cord, and play roles in immunological activities. They also become macrophages, phagocytizing the debris resulting from injury, infections, or diseases in the CNS. Astrocytes and Oligodendrocytes in the CNS Schwann cells in the PNS.

26. Glial Cells Are Support Cells

27. The most numerous of glial cells : irregular shape, roughly star-shaped cell bodies. Function: to support/insulate CNS, recycle neurotransmitters. maintain an adequate 〔 K + 〕 ext Some astrocytes form end-feet on the surfaces of nerve cells in the brain and spinal cord and supply nutrients to these cells. Other astrocytes are involved in the blood brain barrier Types: Protoplasmic: found in gray matter ; Satellite cells Fibrous : found in white matter ; function to repair damaged tissue Muller : modified type found in the retina <number> ASTROCYTES

28. Blood Brain Barrier: Astrocytes and Pericytes

29. <number> Microglia are mobilized after injury, infection, or disease. They arise from macrophages outside the nervous system and are physiologically and embryologically unrelated to the other cell types of the nervous system . A-Protoplasmic astrocytes occur in the gray matter of the central nervous system. B- Fibrous astrocytes are prevalent among myelinated nerve fibers in the white matter of the central nervous system. C-Interfascicular oligodendrocytes are aligned in rows between the nerve fibers of the white matter of the central nervous system D-Perineuronal oligodendrocytes are located in close proximity to the soma of neurons.

30. Take up excess K + in CNS via gap junctions 2. Glutamate regulation 3. Neuronal communication using signaling mechanisms using secondary messengers 4. Regulation of local microcirculation in brain 5. Stores lactate for extra energy <number> Astrocytes NEUROGLIA- FUNCTIONS

31. Glutamatergic Neurons and Astrocytes

32. Smaller than astrocytes Holds nerve fibers together produces myelin sheaths in the CNS Absence of NEUROFILAMENTS In white matter → interfascicular oligodendrocytes In gray matter → perinuclear oligodendrocytes Involved in myelin production <number> OLIGODENDROCYTES

33. Smallest of glial cells Only cell of the CNS derived from mesoderm Respond to trauma and stroke, releases cytokines (TNF-α tumoral necrosis factor) that can be neurotoxic and cause further neuronal damage from inflammation. <number> MICROGLIA

34. Ependym al cells Simple cuboidal/columnar layer of cells lining ventricles/central canal Involved in absorption and CSF flow Choroidal epithelial cells Found in choroid plexus Involved in production and secretion of CSF Have tight junctions to contain CSF <number> EPENDYMAL CELLS

35. EPENDYMAL CELLS

36. Formed by Schwann cells in PNS; oligodendrocytes of CNS Myelinated segments with nodes of Ranvier (rich in Na + channels; allow for saltatory conduction ) <number> MYELINATION

37. Wallerian Degeneration Changes that occur distally to the site of axonal damage, lead to the following changes: The axon swells up, it is broken down and the phagocytosis takes place.

38. Chromatolysis If the injury occurs near or in the cell body. Cell body swells up the Nissl substances become distributed in the cytoplasm and the nucleus moves to the periphery. Debris is phagocytosed by the microglia (PNS). Chromatolysis is the dissolution of the Nissl bodies in the cell body of a neuron. It is an induced response of the cell usually triggered by axotomy, ischemia, toxicity to the cell, cell exhaustion, virus infection.

39. Regeneration in the CNS vs. PNS Axonal regeneration is limited in the CNS as compared to the PNS. Damage to the axon results in the deposition of myelin debris. In the PNS, this debris is cleared rapidly by macrophages. CNS: no macrophages are present in the to clear the debris, impeding neuronal repair, damage attracts astrocytes, which form a glial scar that prevents regeneration, inhibitory components in the myelin such as Nogo, MAG, and OMgp, inhibit neuronal sprouting. PNS: No astrocytes are present in the PNS to induce scarring, neither the inhibitory molecules, which allows for the extension of the growth cone and axonal sprouting.

40. Which one of the following cells in the central nervous system is located in the synaptic region and may function to help confine the neurotransmitters, when released upon stimulation of the neuron, to the synaptic cleft? Astrocyte Oligodendrocyte Pericyte Microglia Satellite cell

41. Which of the following cells would show a rapid increase in number in the cerebral cortex following a localized ischemic insult? Explanation Ischemia ultimately results in cell death of the neurons in the location of the insult. In response to the tissue damage, microglia proliferate and become phagocytic in the damaged area. These cells, as part of the mononuclear phagocytic system may also enter the CNS from the blood vascular system Fibrous astrocytes Microglia Protoplasmic astrocytes Oligodendroglia Ependymal cells

42. Nissl bodies are composed of (A) synaptic vesicles and acetylcholine. (B) polyribosomes and rough endoplasmic reticulum. (C) lipoprotein and melanin. (D) neurofilaments and microtubules. (E) smooth endoplasmic reticulum and mitochondria.

43. Assignment: Presentation next week Describe pathophysiology of Parkinsons disease Multiple sclerosis Amyotrophic lateral sclerosis