block II nervous tissue Flashcards
What are the two principal cells found in the NS?
Neurons and glial cells
Explain neurons
Neurons respond to stimuli by allowing electrical changes in their membrane potential which further generate action potentials. These are transmitted throughout the axon to the synapsis, to communicate with the next cell.
How is the NS divided?
Central Nervous System (CNS): Consists of the brain and spinal cord.
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Peripheral Nervous System (PNS): Consists of cranial, spinal, & peripheral nerves conducting impulses to and from the CNS, and ganglia (collection of cell bodies outside CNS), and specialized nerve endings.
Who received the nobel prize inmedicine in 1906?
Ramon y Cajal and Camillo Golgi
What did Camillo golgi established?
postulates that the nervous system is really a “reticular structure”, a network where this tissue was a continuum, and the cells were forming a developing syncytial system or a system where there was cytoplasmic continuity in the cells of the network.
What did Santiago Ramon y Cajal postulated?
postulates Neurons are independent entities, where each one has a cell body, dendrites, axon and terminals, connecting to other similar cells. This was called “the Neuron doctrine”. His detailed drawings clearly showed dendritic spines.
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Pyramidal neurons of the cerebral cortex
Purkinje cells
Purkinje neurons of the cerebellum
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Image of pyramidal neurons in mouse cerebral cortex expressing green fluorescent protein. The red staining indicates GABAergic interneurons/ flourescense microscopy
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“Brainbow”. These are mice engineered with a gene that includes different fluorescent proteins. The process of recombination cuts out different parts of the gene randomly. Depending on what DNA is excised, a different color results on each cell. This image shows granular neurons in the mouse hippocampus
explain the structure of neurons
Processes extending from cell body also known as soma is the most common characteristic of neurons.
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Dendrite: short processes which transmit impulses from the periphery
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Axon: typically the longest process and transmit information away from cell body.
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Synapse: specialized axon terminals or contacts between neurons
How many neurons are in the human nervous tissue?
There are well over 10 billion neurons in human nervous tissue. In the past, it was believed that there were 10x more glial cells (10:1 ratio between glia and neurons).
Today, using both stereology and isotropic fractionation, it has been shown that the neuron:glia ratio is very similar (1:1)
What are multiolar neurons?
Have one axon and two or more dendrites. Contain various neurotransmitters.
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The majority of neurons are multipolar. e.g. Motor neurons and interneurons of CNS
Examples of multipolar neurons
Motor neurons, pyramidal cell (integrative neuron), interneurons (integrative) and purkinje cell neurons (integrative)
Describe bipolar neurons
They have two processes: These neurons have one axonal branch and one dendritic branch.
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They are most often associated with the receptors for the special senses, such as the sensory epithelia.
Where are bipolar cells present?
They are present in the in the olfactory epithelium, the retina and the hair cells of the inner ear, in the ganglia of the vestibulocochlear nerve.
Describe pseudounipolar neurons?
neurons
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Have one process, the axon that divides close to the cell body into two long axonal branches. The two axonal branches are the conducting units
where can we find pseudounipolar neurons?
Most pseudounipolar neurons are sensory neurons located close to the CNS with cell bodies in the dorsal root ganglia (DRG) and cranial nerve ganglia
What are the functional components of the neuron?
1-The cell body (perikaryon)
2-Dendrites
3- Axon
4- Synaptic junctions
how does the perikaryon looks?
Has characteristics of a protein- producing cell.
What is the perikaryon abundant in?
Contains a large euchromatic (pale) nucleus and prominent nucleolus.
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Perinuclear cytoplasm reveals abundant rER and free ribosomes known as Nissl bodies (basophilia).
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A large perinuclear Golgi apparatus, along with numerous mitochondria and lysosomes.
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Contains a number of neurofilaments (intermediate filaments).
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Neurotubules (microtubules) transport vesicles, and inclusions.
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High levels of synthetic activity needed to maintain these large cells
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This photomicrograph shows a region of the ventral (anterior) horn of a human spinal cord stained with toluidine blue. Features of the nerve cell bodies visible in this image include large, spherical, pale-stained nuclei with a single prominent nucleolus and abundant Nissl bodies within the cytoplasm . Most of the small nuclei belong to neuroglial cells.
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Electron micrograph of a nerve cell body. The cytoplasm is occupied by aggregates of free ribosomes and profiles of rough-surfaced endoplasmic reticulum (rER) that constitute the Nissl bodies of light microscopy. The Golgi apparatus (G) appears as isolated areas containing profiles of flattened sacs and vesicles. Other characteristic organelles include mitochondria (M) and lysosomes (L).
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The cell body of a multipolar neuron as seen on electron micrograph and in a Golgi-stained preparation (inset). rER, rough endoplasmic reticulum
What provides the myelin sheath in CNS?
glial cells called oligodendrocytes
What provides the myelin sheath in PNS?
glial cells called Shwann cells
what is neuropil?
unmyelinated axon
What are the dendrites?
receptor regions
What are the functions of dendrites?
The main function of dendrites is to receive information from other neurons or the external environment
what are dendritic trees?
extensive arborizations that formed by dendrites that significantly increase the receptor surface area
how are dendrites near the cell body?
have a greater diameter than axons and are usually unmyelinated.
Dendrites near cell body contain similar organelles
ribosomes and rER, and small discrete functional Golgi structures not connected with the Golgi apparatus in the cell body. Dendrites further from the cell body with smaller diameter, contain less organelles.
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Purkinje cells in cerebellum stain with specific marker (red
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Golgi stained pyramidal neuron in cerebral cortex showing characteristic shape of cell body and processes
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Electron micrograph showing apical dendrite organelles
by what are dendrites characterized?
characterized by the presence of dendritic spines that are involved in synaptic plasticity, learning, and memory formation
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Cajal’s description of spines, with Golgi staining (1889)
what are dendritic spines?
Many neurons in the CNS have dendrites that can be identified by the presence of dendritic spines. The mushroom-shaped spines are regarded as mature spines and account for the majority (~70% to 80%) of spines found on dendrites.
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Electron microscopy (EM) of spines in pyramidal cells, using high-pressure freezing followed by cryosubstitution of tissue.
Note that dendritic spines are surrounded by a large synaptic button (SB) containing synaptic vesicles. Arrowheads indicate postsynaptic densities.
primary postsynaptic site for signal transduction and signal processing once pre-synaptical vessels reach the memebrane?
spines
what is acquisition of new memories associated with in experimental animals?
increased densoty in pyramidal cells
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Three-dimensional (3D) computer reconstructions of nerve cell.
a. These images represent computer-generated 3D renderings of a single dendrite containing spines. Note the branching pattern of the dendrite.
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Semitransparent rendering of synaptic interactions between dendrite (red) and axon (green). In this image, dendritic spines form five synapses (arrows) with the same axon; the postsynaptic densities are indicated in yellow.
What is the main function of the axon?
convey information away from the cell body to another neuron or to an effector cell. Action Potentials
how many axons does each neuron have and where does it originate from?
one; axon hillock
WHat organelles are not present in the axon hillock?
Large cytoplasmic organelles such as Nissl bodies and Golgi cisternae
what organelles pass thrpugh the axon hillock into the axon?
Microtubules, neurofilaments, mitochondria, and vesicles
What is the AIS?
The region of the axon between the apex of the axon hillock and the beginning of the myelin sheath is called the axon initial segment (AIS). The AIS is the site at which an action potential is generated in the axon.
What is the terminal button?
The axon contains specialized terminal branches with enlarged end bulb also known as a terminal button.
where do axons starts to get myelinated?
after the AIS segment
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Motor neuron in grey matter of spinal cord
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Electron micrograph of a CNS neuron in the region of the axon hillock. the plasma membrane shows undercoating (arrows) and parallel bundles of microtubules and neurofilaments. (myelinated axon)
The undercoat of the axon hillcok is rich in?
voltage dependent sodium channels, and molecules such as beta force spectrin and actin;important in transporting the axonal transport
what is the myelin sheath?
lipid rich layer. Oligodendrocytes in CNS and Schwan cells in PNS make the myelin sheath
what is the function of the myelin sheath?
The myelin sheath ensures the rapid conduction of nerve impulses in the action potentials in the CNS and PNS. Myelin is essential for proper functioning of the nervous system.
What is the golgi type I NEURONS?
have axons that may travel more than a meter to reach their effector targets, e.g. motor neurons.
What is the golgi type II NEURONS?
have very short axons e.g. many interneurons in CNS
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myelinated
What is the importance of microtubules?
Organization of microtubules and their arrangement in axons and dendrites are unique and critical to the functional polarity of neurons
what protein is preferentially involved in dendritic transport?
Dyenin molecular motor;
Why is dendritic transport complex?
due to the antiparallel organization of microtubules
How are microtubules in dendrites arranged?
display a mixed polar orientation. The majority of microtubules in dendrites have reversed polarity with their minus (−) ends directed distally away from the cell body
How is neuronal transport?
bidirectional and serves as a mode of intracellular communication
Mutations in ____ or _________ and ______________ have been directly linked to?
α- or β-tubulin and microtubule-based molecular motors; several neurological disorders
Mutations in TUBA1A cause:
microcephaly, severe motor, intellectual disabilities, and seizures
Mutations in dynein (DYNC1H1) can lead to:
spinal muscular atrophy
What does anterograde transport do?
carries material from the nerve cell body to the axon periphery
Which proteins move the transport vesicles destined toward the (+) ends?
Kinesins; they use ATP
What does RETROGRADE transport do?
carries material from the axon terminal to the nerve cell body.
Which proteins and fcators move the transport vesicles destined toward the (-) ends?
mediated by the MAPs proteins called dyneins that travel along the microtubules toward their minus (−) ends
What are the types of axonal transport?
Slow anterograde
Fast transport system
what is the slow anterograde transport system?
conveys substances from the cell body to the axon terminal at the speed of 0.2 to 4 mm/day in unidirectional way.
What structural elements are transported via slow anterograde transport?
tubulin and actin molecules, calmodulin, and various metabolic enzymes
what is the fast transport system?
conveys substances in both directions at a rate of 20 to 400 mm/day.
Which components are transported via fast transport?
carries sER components, synaptic vesicles, and mitochondria, and low-molecular-weight materials such as sugars, amino acids, nucleotides, some neurotransmitters, and calcium to the axon terminal. its bidirectional and needs ATP
Clinical Relevance: Retrograde transport
Retrograde transport is the pathway followed by toxins and viruses that enter the CNS at nerve endings
Virus Entry Routes into the CNS:
(A) Alpha herpesviruses (e.g.,HSV1,VZV,andPRV) infect pseudounipolar sensory neurons of PNS ganglia. CNS spread is rare and requires anterograde axonal transport of progeny
virions toward the spinal cord.
(B)Rabies virus RABV and polio virus spread via neuromuscular junctions (NMJs) from muscles into soma of motor neurons. Tetanus toxin can also retrogradely be transported
WHat is the synapse?
Specialized junctions between neurons that facilitate the transmission of impulses from one neuron (pre-synaptic) to another (post-synaptic) neuron.
how are synapses classified?
Synapses between neurons may be classified morphologically (axosomatic, axodendritic, and axoaxonic).
What are the 2 other classifications of synapses?
Electrical synapses and chemical synapses
What are Electrical synapses?
commonly seen in invertebrates. Contain gap junctions that permit the movement of ions between cells. Do not require neurotransmitters
What are chemical synapses?
conduction of impulses is achieved by the release of neurotransmitters from pre-synaptic neuron.
Whar is axodendritic synapse?
These synapses occur between axons and dendrites. In the CNS, some axodendritic synapses are found between axons and dendritic spines; most popular
Whar is axosomatic synapse?
These synapses occur between axons and the cell body.
Whar is axoaxonic synapse?
These synapses occur between axons and axons
explain the pathway of synapse
The axon makes several synaptic contacts along the way that are called boutons en passant [Fr. buttons in passing]; then continues, ending finally with an enlarged bouton terminal [Fr. terminal button], or end bulb.
how many synapses are in a neuron?
The number of synapses on a neuron or its processes vary from a few to tens of thousands per neuron.
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Scanning electron micrograph of the nerve cell body. Showing the cell body of a neuron and axon endings forming axosomatic
What is the presynaptic element?
Mainly characterized by presence of synaptic vesicles. SNAREs and synaptotagmin proteins aid in the binding and fusion of vesicles to plasma membrane.
What is the presynaptic density?
“Active zones” where synaptic vesicles are docked and where neurotransmitters are released. Rich in protein-docking complexes.
What is the synaptic cleft?
20- to 30-nm space that separates the pre- and post-synaptic neuron
What is the Postsynaptic component?
Contains receptor sites where neurotransmitters interact. Forms from a portion of plasma membrane of the postsynaptic neuron.
What is the Postsynaptic density?
Elaborate complex of interlinked proteins that serve numerous functions (e.g., anchoring and trafficking of receptors)
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synpases CNS; Neurotransmitters are unidirectional
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Diagram showing neurotransmitter release from a presynaptic knob by fusion of the synaptic vesicles with the presynaptic membrane. The fusion mechanism that involves SNARE proteins the cis-SNARE complex, which is formed after the vesicle fuses to the presynaptic membrane.
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Diagram showing a proposed model of neurotransmitter release via porocytosis. In this model, the synaptic vesicle is anchored and juxtaposed to calcium-selective channels in the presynaptic membrane. In the presence of Ca2+, the bilayers of the vesicle and presynaptic membranes are reorganized to create a 1-nm transient fusion pore connecting the lumen of the vesicle, with the synaptic cleft allowing the release of a neurotransmitter
What determines the type of synaptic response?
The chemical nature of a neurotransmitter and the type of postsynaptic receptors
What are excitatory transmitters?
Excitatory transmitters such as Glutamate prompt the influx of Na+ and Ca2+, which causes depolarization of the post synaptic membrane. Leads to the initiation of an action potential.
What are inhibitory transmitters?
Inhibitory transmitters such as GABA open transmitter-gated Cl- channels causing Cl- to enter the cell and hyperpolarize the postsynpatic membrane, making it less conductive.
on what does the ultimate generation of a nerve impulse (firing) depends ?
on the summation of excitatory and inhibitory impulses reaching neuron.
What is Acetylcholine?
ACh is the neurotransmitter at the neuromuscular junction. ACh is released by the presynaptic sympathetic and parasympathetic neurons and their effectors
What are cholinergic receptors?
The receptors for ACh in the postsynaptic membrane and are divided into two classes.
Muscarine receptors, and Nicotinic receptors
Explain the impact of various drugs in the release of ACh
Various drugs affect the release of ACh into the synaptic cleft as well as its binding to its receptors. For instance, curare, the South American arrow-tip poison, binds to nicotinic ACh receptors, blocking their integral Na+ channels and causing muscle paralysis.
Also Botulinum toxin blocks acetylcholine release
What are catecholamines?
Norepinephrine, epinephrine and Dopamine neurotransmitters secreted by cells in the CNS that are involved in the regulation of alertness, attention, reward, and motivation.
What is Serotonin or 5-hydroxytryptamine (5- HT)?
neurotransmitter; functions as a neurotransmitter in neurons of the CNS and the enteric nervous system (gut). Involved in the regulation of mood, appetite, and sleep.
explain the pathway of serotonin
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After the release of 5-HT, a portion is recycled by serotonin (re-uptake) transporters into presynaptic serotonergic neurons.
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SSRI’s (selective serotonin re-uptake inhibitors) are the most commonly used antidepressants (e.g., Prozac, Paxil, and Zoloft)
how does parkinsons disease start?
A slowly progressive neurologic disorder caused by loss of dopamine (DA) secreting cells in the substantia nigra and basal ganglia of the brain.
This region loses its typical pigmentation, and an increase in the number of glial cells is noticeable (gliosis).
In addition, nerve cells in this region display characteristic intracellular inclusions called Lewy bodies, which represent accumulation of intermediate neurofilaments in association with proteins α-synuclein and ubiquitin.
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Also, responsible for synaptic transmission in the nerve pathways coordinating smooth and focused activity of skeletal muscles.
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Loss of DA-cells is associated with classic pattern of symptoms, including the following:
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Resting tremor in the limb, especially of the hand when in relaxed position.
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Rigidity or increase tone (stiffness) in all muscles.
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Lack of spontaneous movements
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Slowness of movement (bradykinesia) and inability to initiate movement (akinesia)
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Slurred speech, slowness of thought, and small, cramped handwriting.
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The cause of this neurodegenerative disorder is not known, although some evidence suggest a hereditary (~20%) predisposition. L-dopa is a precursor of dopamine and is often the primary agent used to treat Parkinson’s disease.
What are neuroglia?
Supporting Cells of CNS Non-conducting cells that are located close to neurons and referred to as neuroglial cells or simply “glia
The CNS contains four major types of glial cells (central neuroglia):
-Astrocytes
-Oligodendrocytes
-Microglia
-Ependymal cells
Supporting cells in the PNS (peripheral neuroglia) primarily include:
Schwann cells and Satellite cells
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Protoplasmic astrocyte visualized by intracellular labeling method and confocal microscopy. Note the density and spatial distribution of processes(bushy
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Fibrous astrocyte visualized with immunostaining methods that use antibodies against GFAP
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Section of human cerebral cortex, stained with a modified Golgi-gold stain, shows astrocytes with end-feet apposed to a blood vessel.
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Mouse cortical tissue stained with GFAP antibody (red) astrocyte
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Golgi-stained astrocyte with end-feet apposed to a blood vessel
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oligodendrocyte cell
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Photomicrograph of microglial cells (arrows) showing elongated nuclei. In hematoxylin and eosin
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Microglia in a healthy adult mouse retina stained with antibody for Iba1.
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Electron micrograph of microglia showing abundant residual bodies, produced during phagocytic activity.
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ependymal cells
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ependymal cells
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Photomicrograph of the central region of the spinal cord stained with toluidine blue. The arrow points to the central canal.
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At higher magnification, ependymal cells, which line the central canal, can be seen to consist of a single layer of columnar cells
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Transmission electron micrograph showing a portion of the apical region of two columnar ependymal cells. They are joined by a junctional complex (JC) that separates the lumen of the canal from the lateral intercellular space. The apical surface of the ependymal cells has both cilia (C) and microvilli (M). Basal bodies (BB) and a Golgi apparatus (G) within the apical cytoplasm are also visible.
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The astrocytes and their processes interact with the blood vessels as well as with axons and dendrites. Astrocytes processes toward the brain surface, forming the glia limitans. In addition, processes of astrocytes extend toward the fluid-filled spaces in the central nervous system (CNS), where they contact the ependymal lining cells.
Oligodendrocytes are involved in myelination of the nerve fibers in the CNS. Microglia exhibit phagocytotic functions.
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Photomicrograph of an osmium-fixed, toluidine blue–stained peripheral nerve cut in cross section. The axons (A) appear clear. The myelin is represented by the dark ring surrounding the A
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Electron micrograph showing Schwann cells (S) and myelin,
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micrographs showing peripheral nerve fibers at the site of the Ranvier
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micrographs showing peripheral nerve fibers at the site of the Ranvier
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Electro micrograph of unmyelinated axons wrapped by Schwann cell
Electron micrographs of unmyelinated nerve fibers and a single myelinated fiber (MF).
The perineurium (P) cell layers and perineurial cell processes (arrowheads), axons (A) and their Schwann cells and a small blood vessel (BV).
Perineurial cell include an extensive population of actin microfilaments (MF), pinocytotic vesicles (arrows), and cytoplasmic densities (CD). The innermost perineurial cell layer (right) exhibits tight junctions (asterisks) where one cell is overlapping a second cell, forming the sheath
Electron micrograph of peripheral nerve showing myelinated and unmyelinated axons
explain
a. A normal nerve fiber at the time of injury the position of the neuron nucleus and the number and distribution of Nissl bodies. b. When the fiber is injured, the neuronal nucleus moves to the cell periphery, and the number of Nissl bodies is greatly reduced. The nerve fiber distal to the injury degenerates along with its myelin sheath. Schwann cells dedifferentiate and proliferate; myelin debris is phagocytosed by macrophages. c. Proliferated Schwann cells form cellular cords of Bugner that are penetrated by the growing axonal sprouts. The axon grows at a rate of 0.5 to 3 mm/day. d. If growing axonal sprout reaches the muscle fiber, the regeneration is successful and new neuromuscular junctions are developed.
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pyramidal cells in cerebral cortex
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pyramidal cells of cerebral cortex (neurons) Toluidine blue
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CNS cerebral cortex pyramidal cells
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golgi stain of pyramidal cells
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cerebellum purkinjie cells
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cerebellum purkinjie cells
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purkinjie cells cerebellum
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purkinjie cells cerebellum
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purkinjie cells cerebellum
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purkinjie cells cerebellum
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ramon y carjal purkinjie cell neuron
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purkinjie cell (plata y oro stain)
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purkinjie cells cerebellum
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purkinjie cells cerebellum for Niemann pick disease; affects children
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spinal cord, bulls eye pattern (plata con oro) [white matter]
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spinaal cord gray matter and white matter; nissl bodies
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spinal cord; white matter and grey mater
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motoneuron spinal cord
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neurofilaments, myelinated axons; sodium gated channels in the membrane
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motor neuron axon
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motor neurons toluidine blue
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motor neurons silver stain
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chemical synapses the shole thing with vesicles, pre synaptic and postsynaptic; synaptic cleft
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chemical synapses, pre synaptic density, post synaptic density, synaptic cleft, axodentritic synapse
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post synaptic density, pre synaptic density, synaptic cleft, chemical synapse, Microtubules for axonal transport to terminal synapse
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astrocytes imminolabeling GFAP gliap fibrillary acid portein, for staining tumors
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astrocytes
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CNS astrocytes
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astrocytes of retina Glial fibrillary acidic protein
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CNS myelin oligodendrocytes
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microglia
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microglial cells
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silver and gold stain microglial cells
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microglia
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residual bodies of microglia
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ependymal cells
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microvilly ependymal cells; CSF absoroption and secretion
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dorsal root ganglio, pseudounipolar
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dorsal root ganglio, pseudounipolar, satellite cells
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dorsal root ganglio, pseudounipolar, satellite cells
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DRG, satellite cells and drg neuron
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DRG neuron, sensory neuron
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sympathetic ganglion multipolar neuron
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sympathetic ganglion multipolar neurons lipofucin pigments wear n tear
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lipofucsin, sympathetic ganglion multipolar neruons
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lipofucsin, sympathetic ganglion multipolar neruons
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peripheral nerve (schwann cell)
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peripheral nerve (svchwann cell)
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peripheral nerve, epineurum, perineurum, endoneurum,
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perineurium
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perineurium
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peripheral nerve
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peripheral nerve
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myelinated axonen type III ENDONEURIUM
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Node of ranvier; Na channels
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node of ranvier
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neuregulin 1 myelin azxon
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unmyelinated axon
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endoneurium of peripheral nerve
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enteric nervous system (auerbachs plexus)
