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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