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2016-01-10
1
충남의대 해부학교실
김 동 운
Neuroscience
Ch 1: 신경조직
신경계 (nervous system)
중추신경계 (central nervous system, CNS)
뇌 (brain), 척수 (spinal cord)
말초신경계 (peripheral nervous system, PNS)
뇌신경 (cranial nerve), 척수신경 (spinal nerve)]
자율신경계 (autonomic nervous system, ANS)
교감신경계 (symphathetic nervous system)
부교감신경계 (parasymphathetic nervous
system)
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신경계통의 구성 중추신경계 (central nervous system, CNS)
뇌 (brain) + 척수 (spinal cord)
CNS의 보호
Skull (머리뼈)와 vertebral column (척주)
Meninges (뇌척수막)
Cerebrospinal fluid (CSF, 뇌척수액)
구성
Neuron (신경세포) + neuroglia (신경아교세포)
Gray matter (회색질), white matter (백색질)
Gray matter: cell body 위주
White matter: nerve fiber (신경섬유, 주로 axon)위주
Myelin sheath (말이집, 수초)의 지질성분이 반사되어흰빛을 띈다.
말초신경계 (peripheral Nervous system, PNS)
Cranial nerve (뇌신경, 12쌍) + spinal nerve (척수신경, 31쌍)
Nerve fiber의 다발 (bundle)
CNS의 위치에 관한 용어
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The major components of the nervous
system and their functional relationships
신경조직 (nervous tissue)
신경세포 (neuron)
Sensory, motor, interneuron
신경아교세포 (neuroglia)
별아교세포 (astrocyte)
희소돌기아교세포 (oligodendrocyte)
미세아교세포 (microglia)
뇌실막세포 (ependymal cell)
슈반세포 (Schwann cell)
신경절아교세포 (위성세포, 피막세포, satellite cell, capsule
cell)
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Neuron
신경계에서 자극을 받아들이고 정보를 처리하여 효과기에 전달하여반응을 일으킨다
자극의 수용 (excitability, 흥분성)
& 신경흥분의 전달 (conductivity,
전도성)
세포체 (cell body)
핵
핵주위부 (perikaryon)
세포돌기 (cell process)
축삭 (axon)
가지돌기 (dendrite)
Nissle body
Axon hillock
Myelin sheath
Neuromuscular junction
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Unipolar:
DRG (Dorsal root ganglion)
Bipolar:
Bipolar neuron
in retina, cochlear gl.
신경세포의 종류
신경세포의 종류
Golgi type I neuron
Golgi type II neuron
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@ vary in size and shape ; - small granular cells of the cerebellar cortex (10 um)- Betz cells of the motor cortex
and anterior horn cell neuron in the spinal cord (50 um)
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Nucleus
; 핵은 둥글고 크며 대부분세포체의 중간에 위치
Chromatin type
Euchromatin:
Active mRNA transcription
Barr body
Nucleolus
Active rRNA transcription
그림 2-5
Barr body: inactive X chromosome in female
Barr’s the Human Nervous SystemAn Anatomical Viewpoint, 10th Ed.
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Nissl body
abundant, parallally arranged rER cisterna
active site of protein (polypeptide) synthesis
Basophilic: toluidine blue
Chromatolysis
no protein synthesizing assembly in axon
Golgi apparatus: transport vesicle
Mitochondria: cell body, cell process, axon
Nissl body
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그림 2-2 그림 2-3
Cresyl violet Cajal’s silver nitrate staining
AxonNissl substance: rER
• Nucleolus• Coiled body (Collin)
Cytoskeleton
Microtubule: microtubule (MAP)
Actin filament: microfilament
Intermediate filament: Neurofilament I. II: Keratin
III: Vimentin, desmin, GFAP
IV: Nestin
V: nuclear lamin
Tau protein that stabilized microtubule
Neurofibrils Any of the long, thin, microscopic fibrils that run through the body of a neuron
and extend into the axon and dendrites.
Neurofibrillary tangles Aggregates of hyperphosphorylated tau protein that are most commonly knows
as a primary marker of AD.
NF Tau
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Distinctive arrangements
of cytoskeletal elements
in neurons
A: Tubulin: (G) cell body, axon, dendritesTau: (R) microtubule associated protein
axon
B: Hippocampal neuronactin: (R) growing tips of axonal &
dendritic processes
C: Epithelial cellsactin: (R), most of cell body
D: Astrocytesactin: (R), fibrillar bundle
E, F: Neuron, tubulin (G), Processesactin (R), dendritic spine
G: non-neuronal cells
The major features
of neurons
visualized with
microscopy
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손상에 대한 신경세포의 병리학적 반응(reactions of neurons to injury)
1) 급성신경세포 손상(acute neuronal injury--red neuron ;적색신경세포)
- causes
(1) hypoxia/ischemia
(2) infection
(3) toxin
- morphologic features
(1) shrinkage (angularity) of the cell body
(2) pyknosis of the nucleus
(3) disappearance of the nucleolus
(4) intense eosinophilia of the cytoplasm
(5) loss of Nissl substance
- evident with H&E at about 12-24 hrs after insult
2) 아급성 및 만성 신경세포손상(subacute and chronic neuronal injury = degeneration; 변성)
* trans-synaptic degeneration
3) 축삭반응(axonal reaction)
4) neuronal inclusions and intracytoplasmic deposits
(1) viral infections
(2) Lewy bodies in PD, Neurofibrillary tangles in AD
Acute neuronal injury: Neurons are vulnerable to cytotoxic stress. In acute neuronal injury, the cell shrinks, cytoplasm becomes deeply eosinophilic and nucleus appears
pyknotic—the so called “red dead” neuron. In acute hypoxic
encephalopathy, these changes are frequently observed in the cortex (layers III,V), hippocampus (CA1) and cerebellar Purkinje layer
Pyknosis, or karyopyknosis, is the irreversible
condensation of chromatin in the nucleus of a cell
undergoing necrosis or apoptosis.
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Chromatolysis (염색질용해, axonal reaction); When the axon of a neuron is cut or damaged,
1. The cell body swells2. The Nissl bodies disperse and move peripherally3. The nucleus is displaced peripherally in the cell
Pigment
Lipofuscin
melanin
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Cell processes (neurites)
Dendrite
Dedritic spine (가시돌기가시)
Mental retardation
Spines and the strucutural basis of memory
Synaptoneurosome
Polyribosome below
synapses in dendritic
spines
Fragile X mental
retardation protein
(FMRP)
Fragile X syndrome
William Greenough
It was worth the effort.
Axon
Axon hillock: nissl body (X)
분지양상: 축삭곁가지 (axon collateral)
종말가지 (telodendron)
Boutons terminal (신경종말, 종말단추)
축삭의 형질막: axolemma
축삭의 세포질: axoplasma, Nissl body,
golgi (X)
Initial segment: action potential (AP)
@ immunohistochemical markers ; neurofilament protein (NF), neuron specific enolase (NSE), synaptophysin NeuN
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Axon vs. dendrite
Neuroglia (신경아교세포)
Astrocyte
protoplasmic astrocyte
fibrous astrocyte
Oligodendrocyte
perineuronal satellite
cell
interfascicular cell
Microglia
Ependymal Cell
Schwann Cell
in peripheral nerve &
ganglion
Capsular (Satellite) Cell
in ganglion
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Astrocyte (별아교세포)
Physical support for neurons & Energy provision with Glucose uptake
Guiding for migratory neuron
Brain-blood barrier (BBB): regulation of blood flow
Homeostasis of ions (K) and transmitters (Glu, GABA)
Regulation of synapse function & neural activity
Neuronal progenitor from radial glia
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human astrocytes are larger and more complex than rodent and other primates
Heterogeinity of human astrocyte(1) Protoplasmic ; mostly in gray matter, branched process(2) Fibrous ; mostly in white matter, long-thin process(3) Radial astrocyte (glia)(4) Perivascular or Marginal astrocyte: pia mater(5) Velate astrocyte: cerebellum(6) Muller cells: retina(7) Bergmann glia: cerebellum(8) Ependymal cells
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Astrocytes are closely related to cerebral blood vessels
and synapses.
2007 Nature Neuroscience
Tripartite Synapse
- Considered a physical barrier to restrict spill over and diffusion of released molecules to ECS.
- Position of relevance to their functions.
(Araque et al., TINS 22 (1999))
Fellin et al., Physiology 21, 208 (2006)
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Astrocytic reactions to injury
Gliosis (=astrogliosis, reactive astrocyte, astrocyte activation)
; the most important histopathologic indicator of CNS injury
Changing the molecular expression
Changing the morphology
Neural protection and repair by regulation of inflammation
Scar formation
Rosenthal fibers ; eosinophilic, thick, elongated structure in the
astrocytic process
- found in
a. long standing progressive gliosis
b. pilocytic astrocytoma
Brain inflammation and gliosis
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Radial glial cell
Specialized astrocyte
Important during
development of the CNS
Provide pathways for
neuronal growth and
targeting
In adult
Muller cell: retina
Bergmann glia: cerebellum
Microglia
Micro-glia represent around 10-20% of all glial cells with a
number ranging from 100 to 200 billions of cells
depedending on the condition (health vs. disease)
Present in the entire CNS including the spinal cord
There are CNS regions that are more populated than
others and the white mater generally contains less
microglia than the gray matter
Microglial cells are the resident immune cells of the CNS
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Resting (ramified)
Activated
Phagocytic
Microglia
Origin: both macrophages and
microglia derive from myeloid
progenitors
During development
Derive from cirulating monocytes
during the postnatal stage
During adult life
Intact brain: microglia cells self
renew themselves via in situ
proliferation from resident
progenitors
Diseased brain: microglia cells are
replenished from circulating
progenitors (e.g. monocytes)
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Resting microglia
Nimmerjahn et al., Science 308, 1314-1318 (2005)
Microglial cells are highly active in the presumed resting state, continually surveying their microenvironment with extremely motile processes and ramifications. Synaptic pruning
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Microglia: Detrimental vs. Protective
Microglia activation pathway
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Oligodendrocyte
(희소돌기아교세포)
Small, lymphocyte-sized
nucleus with a clear halo ;
fried egg appearance
Function; production and
maintenance of the CNS
myelin
Perineuronal Satellite Cell
Interfascicular Cell
Myelin forming cell in CNS
- Myelin Sheath
Cho et al., 1997
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FIGURE 31-4: Premyelinating and myelinating oligodendrocytes in vivo. Representative images of (A) premyelinating oligodendrocytes from P6 mouse cortex, labeled with EGFP (in Plp -EGFP mice (Mallon et al., 2002) and PLP (Texas Red) or (B) a myelinating oligodendrocyte from mature mouse striatum labeled with EGFP (in Plp -EGFP mice). (Figure 4B reproduced from Mallon et al., 2002).
Copyright © 2012, American Society for Neurochemistry. Published by
Elsevier Inc. All rights reserved.
Nerve fibers
Myelinated
Myelin sheath
Node of Ranvier
OLG (CNS)
Schwann cell (PNS)
Non-myelinated
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Formation of myelin
Mesaxon (축삭간막)
Major dense line
(주치밀선)
Minor dense line
(부치밀선)
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1. trilaminar unit membrane
2. Major dense line: MBP, Shi mice
3. Minor dense line: PLP (jimpy mice), protein 0 (Trembler mice)
4. Cytoplasm of Schwann cell
* 융합하지 않은 면: MAG
Myelin Proteins
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Myelination in CNS
OLG
한세포가 담당하는 신경섬유의 숫자가 최대 60개
하나의 축삭중 여러 마디도가능
Node of Ranvier 존재
말이집틈새 존재
축삭간막이 없다
Ependymal cell
Epithelial Cell
lining ventricular surface
cilia and microvilli on luminal surface
simple cuboidal cell with round nucleus
Tanicyte
basal process, numerous in 3rd ventricle
Choroid Plexus Epithelial Cells
ion transporting cell: numerous mitochondria
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Tanycytes
Figure 25.5 Regeneration in peripheral nerves
1. Cut2. Distal portion degenerates3. Phagocytosed by Macrophages4. Debris is mostly cleared5. Proximal axon stump transforms into a growth cone6. Axon has regrown
Donor graftExercise
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Figure 25.6 Molecular and cellular responses that promote
peripheral nerve regeneration
Figure 25.11 Cellular response to injury in the CNS
MAG
Nogo
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Figure 25.7 Growth-promoting properties of peripheral nerve sheaths and
Schwann cells facilitate growth of damaged axons in the CNS
1. Optic nerve is CNS, therefore, would normally not regenerate through the optic nerve.
2. Now grow through the peripheral nerve graft to reach the SC, a normal target for retinal ganglion cells