Chapter 3
Morphology and Properties of Astrocytes
Sukriti Nag
Abstract
Astrocytes were identified about 150 years ago, and, for the longest time, were considered to be supporting cells in the brain providing trophic, metabolic, and structural support for neural networks. Rearch in the last 2 decades has uncovered many novel molecules in astrocytes and the finding that astrocytes communicate with neurons via Ca2+ signaling, which leads to relea of chemical transmitters, termed gliotransmitters, has led to renewed interest in their biology. This chapter will briefly review the unique morphology and molecular properties of astrocytes. The reader will be introduced to the role of astro-cytes in blood-brain barrier (BBB) maintenance, in Ca2+signaling, in synaptic transmission, in CNS syn-aptogenesis, and as neural progenitor cells. Mention is also made of the dias in which astrocyte dysfunction has a role.
Key words: Astrocyte, Brain edema, Calcium, Cerebral blood flow, Gap junctions, Gliotransmitters, GF
AP, Aquaporin-4, Connexin43, Brain edema, Glutamate, Neural progenitor cells, Synaptic trans-mission, Synaptogenesis, Tripartite synap
1. Introduction
The neuron is well recognized as the principal signaling unit of
neurotransmission and key to the nervous system function while
astrocytes were for the longest time considered to be supporting
电脑文档cells in the brain providing trophic, metabolic, and structural sup-
port for neurons. They were bypasd by neurophysiologists since
they were found to be electrically nonexcitable cells. However,
the finding that they can communicate with neurons via Ca2+ sig-
naling has led to renewed interest in their biology. The last 2海洋里的动物
decades have en an explosion of rearch on astrocytes and it is
now recognized that astrocytes have a much greater role in the
nervous system than just a supportive one. This chapter will
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briefly review the unique morphology and molecular properties
Sukriti Nag (ed.), The Blood-Brain and Other Neural Barriers: Reviews and Protocols, Methods in Molecular Biology, vol. 686, DOI 10.1007/978-1-60761-938-3_3, © Springer Science+Business Media, LLC 2011
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of astrocytes. The reader will be introduced to the role of astrocytes in blood-brain barrier (BBB) maintenance, in Ca 2+ signaling, in synaptic transmission, in CNS synaptogenesis, and as neural pro-genitor cells. Mention is also made of the dias in which astro-cyte dysfunction has a role. This chapter is designed to whet your appetite for astrocyte biology which is reviewed in detail in a recent monograph (1).The interstitial tissue between neurons and blood vesls which contain stellate and spindle-shaped cells was named as “neuro-
glia” or “nerve glue” by Virchow in 1860 (2). About 100 years
ago, u of the gold sublimate staining method showed well-
developed process to emerge from many sides of astrocytes giv-ing them their stellate shape and allowing the
distinction of
astrocytes from other glia (3). Cajal also noted that the tips of astrocytic process having bulbous dilatations or end-feet termi-nated on vesl walls and that astrocytes could form a physical
bridge between neurons and vesls. The Weigert technique (4)
demonstrated the cytoplasmic fibrils in astrocytes and allowed the distinction between fibrillary astrocytes in the white matter, which have abundant fibrils, and protoplasmic astrocytes in the cerebral cortex which have fewer fibrils. Astrocytic process also combine at the surface of the brain to form the glia limitans (Fig. 1a ). The
Bergmann astrocytes of the cerebellum have process predomi-nantly oriented in one direction and
extending all the way from their cell bodies in the Purkinje layer to the surface of the molecu-lar layer, where their end-feet form the glia limitans.
Ultrastructural studies show that astrocytes have relatively
“clear” cytoplasm containing small, highly electron-den gran-ules that are glycogen, and all the usual organelles and lipid drop-lets. Microtubules are rarely en in mature astrocytes. Their
nuclei are oval and contain evenly distributed moderately abun-dant DNA components. A feature of the cytoplasm is the pres-ence of 9-nm
intermediate filaments which may also occur in
parallel bundles in their process (Figs. 2 and 3). Thin short extensions appear to interconnect some of the filaments.Adjacent astrocytes are parated by a 15–20 nm extracellular
space along which two types of junctions are prent. The first type of junction is the puncta adhaerentia where adjacent astro-cyte membranes are parallel being parated by a wider space of 25–30 nm (5). Slightly incread electron density of the gap and
adjacent cytoplasm is also prent. The cond type of junction is the gap junction where adjacent membranes are parated by a 2- to 3-nm wide gap (Fig. 3). Both junctions allow the penetration of tracers such as horradish peroxida and lanthanum (6).
法西斯是什么意思2. Morphology and Anatomic Distribution of Astrocytes
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Fig. 1. Merged confocal images from rat brain dual-labeled for GFAP (red) and Claudin-5 (green) (a, c, e, and g), for caveolin-3 and GFAP (d), and zonula occludens-1 (ZO-1) and aquaporin4 (AQP4) (f ) are shown. (a) The glia limitans formed by astrocytic process is prent at the brain surface and astrocytic end-feet surround the entire circumference of two intracerebral arterioles. (b) One-month-old postnatal rats showing two protoplasmic astrocytes, one filled with Lucifer Yellow (green) and the other with Alexa 568. Astrocytic domains are well established and the fine spongiform process of adjacent astrocytes intermingle in an area only a couple of microns wide. (c) Fibrillary astrocytes of the white matter have few process and the long axes of the cells are parallel to the white matter axons. (d) Normal rat brain shows colocal-ization (yellow ) of caveolin-3 and GFAP in the white matter and in hippocampal astrocytes. (e) A large cortical vesl shows the termination of end-feet in the form of looped process (arrowhead ). (f ) Vesl gment shows endothelial ZO-1fibrils (green) surrounded by astrocytic foot process which are immunoreactive for AQP4 (red, arrowhead ). (g) Reactive astro-cytosis adjacent to a cortical cold lesion is shown. The density and size of astrocytes are incread. Note also that their process terminate into multiple mini process which form a network (arrowheads). (f) Scale bar = 50 m m (a, c–e, g);
10 m m (b) and 20 m m (f ). (b) Reproduced with permission (13); (f ) reproduced with permission (64).
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Fig. 2. An electron micrograph of an astrocyte in layer 3 of the cerebral cortex shows relatively electron-lucent cytoplasm in which the normal complement of organelles is prent. Groups of 9-nm intermediate filaments are prent in the cytoplasm (arrowheads ). ×18,500.
Fig. 3. An electron micrograph taken at the level of layer 3 of the cerebral cortex shows an arteriolar gment which consists of endothelial, smooth muscle, and attenuated leptomeningeal cell layers. The latter is parated from two astrocytic end-feet (A ) by a bament membrane. Note that in well-fixed vesls, a perivascular space is not prent. The end-feet show mito-chondria and the cross-ctions of intermediate filaments (arrowheads ) in the cytoplasm and are parated by a gap junction (*). Note the proximity of the end-feet to pre- and postsynaptic terminals which together form a tripartite synap. ×50,000.
73Morphology and Properties of Astrocytes Gap junctions are evenly distributed along the astrocytic process, often interconnecting adjacent astrocytic process derived from the same cell referred to as autocellular junctions (7, 8). Only in the narrow interface of adjacent cells do gap junc-tions couple process from different cells (9). At the gap junc-tion, each of the joined cells contributes a hemi-channel or connexon to each cell–cell channel. Each hemi-channel compris a hexamer of connexins arranged around a central pore, and the cell–cell channels are gated by veral stimuli, including transjunc-tional voltage, low pH, and various pharmacological agents. Connexin30 and connexin43 colocalize at gap junctions (10). Zonula occludens-1 (ZO-1) has also been localized at astrocytic gap junctions where it is found to colocalize with connexin30 and 43 and ZONAB (ZO-1-as
sociated nucleic acid-binding protein) (11). Connexins are known to have adhesive properties and the autocellular junctions may stabilize the complex network of astro-cytic process and may also facilitate intracellular diffusion of energy metabolites and possible signaling molecules, such as Ca 2+ and inositol (1,4,5)-triphosphate (IP 3), between fine astrocytic process (8).Astrocytes typically extend between five to eight major process, each of which is highly ramified into innumerable delicate leaflet-like process, which are insinuated between and around the vari-ous components of the nervous tissue (12). Microinjection of
single hippocampal astrocytes with fluorescent dyes demonstrates that each astrocyte occupies a discrete area that is free of process from any adjacent astrocytes thus defining its own anatomical domain (Fig. 1b ). Only the most peripheral process interdigi-tate with one another in a narrow interface within which <5% of the volumes of adjacent astrocytes overlap (13, 14). Glial fibril-lary acidic protein (GFAP) labels only the major process of astrocytes, many of the smaller process being nonreactive with GFAP . The smaller process fill a volume that is best defined as a polyhedron (12–14). The fine process have a significantly higher density of mitochondria as compared with the surround-ing neuronal process, synaps, other glial process, and endothelial cells, supporting the concept that oxidative metabo-lism is a major part of the energy met
主要表现
abolism in protoplasmic astrocytes (15).Within a single astrocyte domain, 300–600 neuronal den-drites (16) and 105 synaps are prent in the rodent cortex and hippocampus. In contrast, in the human cortex, a single astrocyte might n the activity and regulate the function of more than one million synaps within its domain (17). The distribution of astrocytes throughout the brain and spinal cord is highly orga-nized being evenly distributed, such that their cell bodies and larger process are not in contact with each other (18).
2.1. Astrocyte
Domains
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The functional significance of the nonoverlapping astrocytic domains is unknown, although all synaps lying within a given volumetrically defined compartment may be under the sole influ-ence of a single astrocyte (19).Neurons are disperd among the astrocytic domains, with the innumerable fine neurites penetrating each astrocytic domain and being surrounded by its process. The ratio of glia to neu-rons is higher in humans than most other species (19–21).Bad on GFAP immunostaining, human cortical astrocytes are reported to have four distinct morphologies
being named protoplasmic, interlaminar, polarized, and fibrous or fibrillary astrocytes (17).Protoplasmic astrocytes are the most abundant type in human cortex, being prent in cortical layers 2–6. Human protoplasmic astrocytes are larger and more elaborate than their rodent coun-terparts (22). Although the cell body of human astrocytes is only ~10 m m in diameter, their process span 100–200 m m, giving them a 27-fold greater volume than their rodent counterparts (17). The synaptic density in the rat cortex has been estimated to be 1,397 million synaps/mm 3, while that of human cortex is ~1,100 million synaps/mm 3 (23). This suggests that synaptic density alone does not account for the incread capacity of human brain. The majority of the GFAP-positive process of protoplasmic astrocytes do not overlap indicating a domain organization.Interlaminar astrocytes were first described in cortical layer 1 of primate cortex (24, 25) where they extend striking long, fre-quently unbranched, process extending through the cortical layers, terminating in layers 3 or 4 (26). The cell bodies of the astrocytes are ~10 m m in diameter and extend two types of pro-cess: three to six fibers that contribute to the astrocytic network near the pial surface, and another one or two that penetrate deeper layers of the cortex. The latter have a constant diameter and can extend up to 1 mm in length (26). The process are tortuous and, although largely unbranched, occasionally nd collaterals to the vasculature (26). The endings of the interlaminar fibers deep in the cortex might be in the form of a “terminal mass” or end bulb containing a multilami
nar structure and mitochondria (27). The function of the interlaminar astrocytes is unknown. Their interlaminar fibers clearly violate the domain organization and might rve as a nonsynaptic pathway for long-distance sig-naling and integration of activity within cortical columns (17).The unipolar cells are relatively uncommon and are prent in layers 5 and 6 of the cortex, near the white matter, and extend 2.2. Types
of Astrocytes in the Human Cerebral Cortex
2.2.1. Protoplasmic Astrocytes
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2.2.2. Interlaminar Astrocytes
2.2.
3. Polarized Astrocytes
