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1.

The Schwann cell


Origin: neural cell crest
2 phenotypes, derived from a common precursor
Myelinizing type express myelin markers (e.g. MBPs- myelin basic proteins,
glicoprotein P0)
Non-myelinizing type
LM: dark nuclei
around nerve fibers
EM:
Cell membrane surrounded by basal membrane
2 cytoplasmic domains
role:
Myelinization
Axonal growth/sprouting guidance
Modulate synaptic transmission

2. Neurogenesis in adult life; neural stem cells


Generation of new neurons in adult life
-in the dentage gyrus of hippocampus
neural stem cells
Undifferentiated
Nestin-positive
Multipotent
Self renewal
Highly mobile in pathologic circumstances
Neural stem cell niche
Formed by astroglia, microglia and endothelial cells
Populated with renewal cells, intermediate progenitors (mitotically active) and
neuroblasts
Self-renewing neural stem cells in the subgranular zone of the adult
hippocampal dentate gyrus (also referred to as Type-1 cells)
produce intermediate progenitor cells (IPs, Type-2a cells), NeuroD1 and
Doublecortin-positive neuroblasts (Type-2b) and subsequently granule neurons.
Type-1 neural stem cells have their cell bodies in the subgranular zone and
extend a long process through the granule cell layer to the overlaying
molecular layer.
Type-2 cells are transient intermediate progenitors.
They also have their cell body in the subgranular zone but lack a long radial
process and have a more rounded morphology with short stubby processes.
Neuroblasts by contrast extend a leading process and migrate into the granule
cell layer.

Whereas radial Type-1 cells are quiescent, Type-2 cells divide readily
expanding the progenitor pool.

Modulation of adult neurogenesis


Inhibitory influences:
Ageing
Stress
Cortisol
Alcohol
enhancement effect
learning
ovarian hormones
dopamine
growth factors (EGF, IGF- I)
Physical exercise

3. What is the gray matter? Please give examples of histological


organization of gray matter in the central nervous system
Grey matter in the brain = cortex, are made of:
Perikaryons
Mostly unmyelinated fibers (the initial part of their axons and the dendrites)
Protoplasmic astrocytes
Oligodendrocytes
Microglial cells
Spinal cord:
The grey matter
has the shape of an H
Is centrally located
Cerebral cortex:
Has 6 layers:
Molecular layer
Homogenous aspect
Few small neurons
Numerous fibers
External granular layer
Small granule cells
many neuroglial cells
External pyramidal layer
The thickest layer in the section of the cerebral cortex

Consists of pyramidal cells and some granule cells, as well as


numerous neuroglia (Ng)
Internal granular layer
Small and a few large granule cells
Neuroglial cells
Internal pyramidal layer
Large pyramidal neurons Betz neurons
Polymorph layer
Cells of various shapes, many of which are fusiform
Cerebellum
The cortex has 3 layers:
The molecular layer outer
Few perikaryons - The less dense appearance is due to the sparse
arrangement
Many unmyelinated axons of the granule cells
The Purkinje cells layer central
Largest neurons
The dendrites divide repeatedly in one plane
displays a large nucleus
send their axons into the granular layer
The granular layer inner
Smallest neurons granule cells
the darker appearance is due to the great number of darkly staining
nuclei packed closely together
Few dendrites, one axon

4. Formation of cerebrospinal fluid


Produced by the choroid plexus (500 ml / day) and the extracellular fluid flow
through the epithelium ependymal circumventricular organs
The amount of 150 ml: 30 ml in the ventricles, 120 ml the subarachnoid
space.
CSF flows from the lateral ventricles ventricle III ventricle IV
subarachnoid space
From the subarachnoid space - a small fraction flows through the spaces
around spinal and cranial nerve roots (perineural)
Most of it flows through specializations arachnoid (arahnoidiene villi) in the
sinuses large vein thickness dura
CSF secretion involves the transport of ions ( Na+, Cl and HCO3) across the
epithelium from blood to CSF.
an osmotic gradient that drives the unidirectional transport of ions across an
epithelium.

Functions:
- Maintain the necessary brain fluid
- Mechanical Protection
- Communicate easily with extracellular fluid CSF-brain barrier because (cells
ependymal) is permeable
- Nervous tissue metabolites excretion
- Uptake by brain from CSF substances necessary

5. Meninges

Dura mater dense connective tissue, layered by fibroblasts connected by


desmosomes and gap junctions
Subepidural space
Subdural space
Arachnoid
Outer layer epithelial cells connected by tight junctions
Inner layer fibroblast with elongations(trabeculae)
Arachnoid villi
The subarachnoid space is filled with cerebrospinal fluid
Pia mater loose connective tissue
Glia limitans interdigitating astrocytic on the surface of the CNS. This layer
seals the surface of the CNS and dips into brain tissue along the perivascular
(Virchow-Robin) spaces.

6. Peripheral nervous system: histologic organization of nerves

Ganglia groups of neurons, accompanied by glial cells.


on nerves trajectories :
dorsal root ganglia
autonomic ganglia
Nerves axonal projections of neurons, enwrapped in Schwann cells and connective
tissues sheaths
Dorsal root ganglia
Sensitive
On the dorsal roots of the spinal nerves
Cortical zone- in the periphery:
The round bodies of pseudounipolar neurons
Small and large
A continuous capsule of SATELLITE CELLS small cuboidal cells
enveloped by a thin layer of connective tissue
Medullary zone in the center:

Mostly myelinated nerve fibers


Autonomic ganglia
Dilatations on the autonomic nerves
The arrangement of the cell bodies within the ganglion appears to be haphazard
Multipolar neurons star-shaped
smaller than spinal ganglion neurons
Some of the cells contain yellow lipofuscin granules, a sign of age
Discontinuous capsule of satellite cells
Connective tissue surrounding the satellite cell capsule
Satellite cells
Located around nerve cell bodies in ganglia
Myelinated nerves
Schwann cell enwrapping axonal segment
Ranvier node between Schwann cells, covered by interdigitated cellular
processes
Internode- up to 1mm
Unmyelinated nerves
Associate with Schwann cells
1 Schwann cell / multiple axons
the axons may or may not present a mesaxon
external lamina
Nerve-associated connective tissue

Composed by :
Myelinated nerve fibers
Connective tissue:
Endoneurium
Surrounds each nerve fiber
A thin layer of reticular fibers
Prineurium
Surrounds a bundle of nerve fibers
Outer connective tissue layer
Inner layer of flattened epithelial cells
conducts small blood vessels
Epineurium
loose connective tissue with numerous fat cells

Surrounds the entire nerve

86. Classification of neurons, examples of particular types of neurons.


Shape of cell body: pyramidal, star-shaped, granular, round,
fusiform
Size
large > 100m,
small 10 m
No. of processes
Unipolar dorsal root ganglia
Bipolar olfactory and retinal neurons
Multipolar Purkinje cells, pyramidal neurons (Betz
neurons)
Function
Sensory (afferent) transmit impulses toward the CNS
Motor (efferent) carry impulses away from the CNS
Interneurons (association neurons) lie between sensory and
motor pathways and shuttle signals through CNS pathways
87. Structure and ultrastructure of different types of neuroglia: astrocytes,
oligodendrocytes, microglia, ependymal cells.
Roles:
Provide a supportive scaffold for neurons
Segregate and insulate neurons
Produce chemicals that guide young neurons to the proper
connections
Promote health and growth
Astrocyte:
o Most abundant, versatile,
o Star-shaped with many processes highly branched
glial cells
o Cling to neurons, synaptic endings, and cover nearby
capillaries
o Support and brace neurons
o Anchor neurons to nutrient supplies
o Guide migration of young neurons
o Control the chemical environment (recapture K+ ions
and neurotransmitters)
o Two types:

protoplasmatic: mostly in gray matter, numerous


processes, short and ramified
fibrous: mostly in white matter, fewer processes
and longer
Oligodendrocyte:
o
o
o
o

Majority of CNS cellularity


Found in both white and gray matter
Form myelin sheath of axons in CNS
Small round, nuclei, with processes surrounding several
axons
o branched cells that line the thicker CNS nerve fibers
Microglia:

Phagocitic cells originating from bone marrow


In both white and gray matter
Small, elongated cells
Short, twisted processes, covered with spines

Ependimal cells:
range in shape from cuboidal to columnar, many are ciliated
Line the central cavities of the brain and spinal column
Tight junctions at apical pole, infoldings at basal pole,
connecting with astrocytes
88. General organization of a neuron. Axonal transport
Neurons are composed of:
1. Soma (perykarion)
2. processes
Dendrites
Axon
Axon hillock
Terminal arborization
Synaptic buttons
1. perykarion = cell body
Nucleus: centrally, euchromatic with visible nucleolus

The major biosynthetic center


Has no centrioles
Has well-developed Nissl bodies (rough ER)
Axon hillock cone-shaped area where axons arise
Basophilic granules = Nissl bodies RER and ribosomes
Only in perykarion
Neurofilaments and microtubules visible in silver staining
In both perykarion and processes
Lipofuscin
2. a. dendrites
Usually numerous
Branched
Contain rER
Contain receptors to neurotransmitters
Sends signals to soma
Presents spines (Spines are neuronal protrusions, each of which
receives input typically from one excitatory synapse)
Dendritic spines- structure
Post synaptic densities glutamate receptors
Core of actin filaments and actin associated proteins
Endocytic compartment
Organelles ribosomes, special ER (only in some)
2. b. axon
1 per soma
Initial segment from axon hillock
Transmits AP away from soma
No Nissl bodies
Neurofilaments
MT
Axon collaterals
Axon terminals
Axonal transport:
Anterograde - kinesin
Retrograde dynein
Growth factors and recycled membranes
Some viruses, toxins, noxious agents

Slow transport only anterograde, for structural components


Fast transport bidirectional
membrane components and neurotransmitters
89. Classification of synapses.
According to funtion:
Electrical
o Less common than chemical synapses
o Gap junctions allow neurons to be electrically coupled as
ions can flow directly from neuron to neuron - provide a
means to synchronize activity of neurons
o
Are important in the CNS in:
Arousal from sleep
Mental attention and conscious perception
Emotions and memory
Ion and water homeostasis
o Abundant in embryonic nervous tissue
Chemical
According to location:
o Axo-dendritic
o Axo-axonic
o Axo-somatic
90. Describe the structure of a chemical synapse
Synapse is a junction that mediates information transfer from one neuron
to another neuron or to an effector cell
Is composed of:
1. Presynaptic knob
Synaptic vesicles neurotransmitters
Mithocondria
Presynaptic density/Active zone: electron dense thickening of
the presynaptic membrane, where synaptic vesicles accumulate
and dock
Scaffolding and anchoring proteins needed for synaptic vesicular
cycle
2. Synaptic Cleft

Fluid-filled space separating the presynaptic and postsynaptic


neurons, prevents nerve impulses from directly passing from
one neuron to the next
Transmission across the synaptic cleft:
Is a chemical event (as opposed to an electrical one)
Ensures unidirectional communication between neurons
3. Postsynaptic component part of neurilemma of postsynaptic
neuron, containing receptors for neurotransmitters
o postsynaptic density
91. Describe the steps of neurotransmitter vesicle traffic
Synaptic vesicles cycles - STEPS:
Trafficking to the synapse by kinesins
Transmitter Loading happens at synaptic site!
an active processes requiring a specific neurotransmitter transporter
and a vacuolar-type proton pump ATP-ase Docking
Docking dependent on small GTPases
Fusion to presynaptic membrane
Ca-dependant, by activation of synaptogamins
Incomplete: kiss and run
Complete: exocitosis
Endocytosis
Clathrin-depenedent
Neurotransmitter clearance
Reuptake in the presynaptic compartment by membrane
transporters (dopamine)
Metabolization in the synaptic cleft (acetylcholine)
92. The Schwann cell
Origin: neural cell crest
2 phenotypes, derived from a common precursor
Myelinizing type express myelin markers (e.g. MBPs- myelin
basic proteins, glicoprotein P0)
Non-myelinizing type
LM: dark nuclei
around nerve fibers
EM:

role:

Cell membrane surrounded by basal membrane


2 cytoplasmic domains
Myelinization
Axonal growth/sprouting guidance
Modulate synaptic transmission

93. The myelin sheath in central and peripheral nervous systems


Whitish, fatty, segmented sheath around most long axons
Protects the axon
Electrically insulates fibers from one another
Increases the speed of nerve impulse transmission
Produced by supportive cells:
Oligodendrocyte in CNS
Schwann cell in PNS
94. Neurogenesis in adult life; neural stem cells
Generation of new neurons in adult life
-in the dentage gyrus of hippocampus
neural stem cells
Undifferentiated
Nestin-positive
Multipotent
Self renewal
Highly mobile in pathologic circumstances
Neural stem cell niche
Formed by astroglia, microglia and endothelial cells
Populated with renewal cells, intermediate progenitors (mitotically
active) and neuroblasts
Self-renewing neural stem cells in the subgranular zone of the adult
hippocampal dentate gyrus (also referred to as Type-1 cells)
produce intermediate progenitor cells (IPs, Type-2a cells),
NeuroD1 and Doublecortin-positive neuroblasts (Type-2b) and
subsequently granule neurons.

Type-1 neural stem cells have their cell bodies in the subgranular
zone and extend a long process through the granule cell layer to the
overlaying molecular layer.
Type-2 cells are transient intermediate progenitors.
They also have their cell body in the subgranular zone but lack a
long radial process and have a more rounded morphology with
short stubby processes.
Neuroblasts by contrast extend a leading process and migrate into
the granule cell layer.
Whereas radial Type-1 cells are quiescent, Type-2 cells divide
readily expanding the progenitor pool.
Modulation of adult neurogenesis
Inhibitory influences:
Ageing
Stress
Cortisol
Alcohol
enhancement effect
learning
ovarian hormones
dopamine
growth factors (EGF, IGF- I)
Physical exercise
95. The Choroidal plexus: structure, ultrastructure, physiological role
FOLDS OF PIA MATER WITH FENESTRATED
CAPILLARIES. FOUND IN 3RD AND 4TH VENTRICLES
The choroid plexus, is a tuft of capillaries covered by a special
cuboidal epithelium
Epithelial cells (cuboidal epithelium)
o tight junctions
o polarised epithelial cells
o apical membrane (ventricle facing) numerous micovilli
o basolateral membrane (blood facing) many infoldings
Capillaries

o fenestrated, non-continuous and have gaps between the


capillary endothelial cells allowing the free-movement of
small molecules
96. Structure of meninges: dura matter, arachnoid and piamatter.
Dura mater dense connective tissue, layered by fibroblasts connected
by desmosomes and gap junctions
Subepidural space
Subdural space
Arachnoid
Outer layer epithelial cells connected by tight junctions
Inner layer fibroblast with elongations(trabeculae)
Arachnoid villi
The subarachnoid space is filled with cerebrospinal fluid
Pia mater loose connective tissue
Glia limitans interdigitating astrocytic on the surface of the CNS.
This layer seals the surface of the CNS and dips into brain tissue
along the perivascular (Virchow-Robin) spaces.
97. Peripheral nervous system: histologic organization of nerves
Composed by :
Myelinated nerve fibers
Connective tissue:
Endoneurium
Surrounds each nerve fiber
A thin layer of reticular fibers
Prineurium
Surrounds a bundle of nerve fibers
Outer connective tissue layer
Inner layer of flattened epithelioid cells
conducts small blood vessels
Epineurium
loose connective tissue with numerous fat cells
Surrounds the entire nerve
Myelinated nerves
Schwann cell enwrapping axonal segment

Ranvier node between Schwann cells, covered by interdigitated


cellular processes
Internode- up to 1mm
Unmyelinated nerves
Associate with Schwann cells
1 Schwann cell / multiple axons
the axons may or may not present a mesaxon
external lamina
98. Peripheral nervous system: histologic organization of ganglia
Ganglia
Ovoid structures
Surrounded by connective tissue
Classification
Sensitive
Cranial
Spinal
Autonomic
Laterovertebral
Paravertebral
Intramural
Dorsal root ganglia
Sensitive
On the dorsal roots of the spinal nerves
Cortical zone- in the periphery:
The round bodies of pseudounipolar neurons
Small and large
A continuous capsule of SATELLITE CELLS small cuboidal
cells enveloped by a thin layer of connective tissue
Medullary zone in the center:
Mostly myelinated nerve fibers
Autonomic ganglia
Dilatations on the autonomic nerves

The arrangement of the cell bodies within the ganglion appears to


be haphazard
Multipolar neurons star-shaped
smaller than spinal ganglion neurons
Some of the cells contain yellow lipofuscin granules, a sign of age
Discontinuous capsule of satellite cells
Connective tissue surrounding the satellite cell capsule
Satellite cells
Located around nerve cell bodies in ganglia

99. The blood-brain barrier.


Structural and functional barrier which impedes and regulates the influx
of most compounds from blood to brain
Formed by brain microvascular endothelial cells (BMEC), astrocyte end
feet and pericytes
Essential for normal function of CNS
Regulates passage of molecules in and out of brain to maintain neural
environment.
cerebral capillaries have:
Tight continuous quintuple-layered intercellular junctions
low wall thickness (0.2 um)
higher mitochondrial content
thick basement membrane
Highly selective transport mechanisms
Allows passage/transport of small molecules (H2O, O2, CO2),
lipophilic molecules (EtOH, heroin), passive transport of
glucose, active transport of amino acids/NT precursors
Prevents passage of larger molecules (dopamine), charged
molecules, etc
100. General hystological organization of central nervous system organs:
spinal cord, cerebral hemispheres, cerebellum.
Grey matter in the brain = cortex, are made of:
Perikaryons
Mostly unmyelinated fibers (the initial part of their axons and the
dendrites)
Protoplasmic astrocytes

Oligodendrocytes
Microglial cells
White matter:
Mostly myelinated fibers
Oligodendrocytes
Fibrous astrocytes
Microglial cells

Spinal cord:
White matter is peripheral
Grey matter is central the shape of an H
The central canal lined by ependymal cells
Parenchymal organ
Composed of perikaryons and nerve fibers
The grey matter
has the shape of an H
Is centrally located
The anterior horn
Contains motor, multipolar neurons
The posterior horn
Contains sensitive, multipolar neurons
Receives sensory fibers from the spinal ganglia
Cerebral cortex:
The cortex - grey matter
The surface is increased by gyri
The central area - white matter
Has 6 layers:
Molecular layer
Homogenous aspect
Few small neurons
Numerous fibers
External granular layer
Small granule cells
many neuroglial cells

External pyramidal layer


The thickest layer in the section of the cerebral cortex
Consists of pyramidal cells and some granule cells, as well
as numerous neuroglia (Ng)
Internal granular layer
Small and a few large granule cells
Neuroglial cells
Internal pyramidal layer
Large pyramidal neurons Betz neurons
Polymorph layer
Cells of various shapes, many of which are fusiform
Cerebellum
Many furrows divide the organ into lobules
Each lobule has
a superficial layer of grey matter
A core of white matter
The cortex has 3 layers:
The molecular layer outer
Few perikaryons - The less dense appearance is due to the
sparse arrangement
Many unmyelinated axons of the granule cells
The Purkinje cells layer central
Largest neurons
The dendrites divide repeatedly in one plane
displays a large nucleus
send their axons into the granular layer
The granular layer inner
Smallest neurons granule cells
the darker appearance is due to the great number of darkly
staining nuclei packed closely together
Few dendrites, one axon

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