Neuroscience Ch 1: 신경조직 충남의대해부학교실김동운 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) 1
신경계통의구성 중추신경계 (central nervous system, CNS) 뇌 (brain) + 척수 (spinal cord) CNS 의보호 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 ) 의지질성분이반사되어흰빛을띈다. 말초신경계 (peripheral Nervous system, PNS) Cranial nerve ( 뇌신경, 12 쌍 ) + spinal nerve ( 척수신경, 31 쌍 ) Nerve fiber 의다발 (bundle) CNS 의위치에관한용어 2
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) 3
Neuron 신경계에서자극을받아들이고정보를처리하여효과기에전달하여반응을일으킨다 자극의수용 (excitability, 흥분성 ) & 신경흥분의전달 (conductivity, 전도성 ) 세포체 (cell body) 핵 핵주위부 (perikaryon) 세포돌기 (cell process) 축삭 (axon) 가지돌기 (dendrite) Nissle body Axon hillock Myelin sheath Neuromuscular junction 4
신경세포의종류 Unipolar: DRG (Dorsal root ganglion) Bipolar: Bipolar neuron in retina, cochlear gl. 신경세포의종류 Golgi type I neuron Golgi type II neuron 5
@ 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) 6
Nucleus ; 핵은둥글고크며대부분세포체의중간에위치 Chromatin type Euchromatin: Active mrna transcription Barr body 그림 2-5 Nucleolus Active rrna transcription Barr body: inactive X chromosome in female Barr s the Human Nervous System An Anatomical Viewpoint, 10 th Ed. 7
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 8
Cresyl violet Cajal s silver nitrate staining 그림 2-2 그림 2-3 Nissl substance: rer Axon 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 NF Tau 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. 9
Distinctive arrangements of cytoskeletal elements in neurons A: Tubulin: (G) cell body, axon, dendrites Tau: (R) microtubule associated protein axon B: Hippocampal neuron actin: (R) growing tips of axonal & dendritic processes C: Epithelial cells actin: (R), most of cell body D: Astrocytes actin: (R), fibrillar bundle E, F: Neuron, tubulin (G), Processes actin (R), dendritic spine G: non-neuronal cells The major features of neurons visualized with microscopy 10
손상에대한신경세포의병리학적반응 (reactions of neurons to injury) 1) 급성신경세포손상 (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) 아급성및만성신경세포손상 (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. 11
Chromatolysis ( 염색질용해, axonal reaction) ; When the axon of a neuron is cut or damaged, 1. The cell body swells 2. The Nissl bodies disperse and move peripherally 3. The nucleus is displaced peripherally in the cell Pigment Lipofuscin melanin 12
Cell processes (neurites) Dendrite Dedritic spine ( 가시돌기가시 ) Mental retardation Spines and the strucutural basis of memory William Greenough Synaptoneurosome Polyribosome below synapses in dendritic spines Fragile X mental retardation protein (FMRP) Fragile X syndrome It was worth the effort. Axon Axon hillock: nissl body (X) 분지양상 : 축삭곁가지 (axon collateral) 종말가지 (telodendron) Boutons terminal ( 신경종말, 종말단추 ) 축삭의형질막 : axolemma 축삭의세포질 : axoplasma, Nissl body, golgi (X) Initial segment: action potential (AP) @ immunohistochemical markers ; neurofilament protein (NF), neuron specific enolase (NSE), synaptophysin NeuN 13
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 14
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 15
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 16
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) 17
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 18
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 19
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) 20
Resting microglia Microglial cells are highly active in the presumed resting state, continually surveying their microenvironment with extremely motile processes and ramifications. Synaptic pruning Nimmerjahn et al., Science 308, 1314-1318 (2005) 21
Microglia: Detrimental vs. Protective Microglia activation pathway 22
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 23
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 24
Formation of myelin Mesaxon ( 축삭간막 ) Major dense line ( 주치밀선 ) Minor dense line ( 부치밀선 ) 25
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 * 융합하지않은면 : MAG Myelin Proteins 26
Myelination in CNS OLG 한세포가담당하는신경섬유의숫자가최대 60 개 하나의축삭중여러마디도가능 Node of Ranvier 존재 말이집틈새존재 축삭간막이없다 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 27
Tanycytes Figure 25.5 Regeneration in peripheral nerves 1. Cut 2. Distal portion degenerates 3. Phagocytosed by Macrophages 4. Debris is mostly cleared 5. Proximal axon stump transforms into a growth cone 6. Axon has regrown Donor graft Exercise 28
Figure 25.6 Molecular and cellular responses that promote peripheral nerve regeneration Figure 25.11 Cellular response to injury in the CNS MAG Nogo 29
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 30