astrocytes Play Starring Role

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Source: Medical Institute (http://www.hhmi.org/)

Date: Posted 5/6/2002

Astrocytes Play Starring Role In Neural Stem Cell Development

Researchers have discovered that astrocytes -- brain cells once thought to

be little more than a component of the supportive scaffold for neurons --

may actually play a starring role in triggering the maturation and

proliferation of adult neural stem cells. The studies also suggest that

growth factors produced by astrocytes may be critical in regenerating brain

or spinal tissue that has been damaged by trauma or disease.

The discovery that astrocytes are important for neuronal maturation, or

neurogenesis, was reported in the May 2, 2002, issue of the journal Nature

by Medical Institute investigator F. s and

colleagues Fred H. Gage and HHMI research associate Hong-jun Song at The

Salk Institute.

Neurons are the key information-carrying cells in the central nervous

system. All neurons, as well as other types of brain cells, arise from

immature neural stem cells, which have the potential to develop into any

kind of cell in the central nervous system.

According to s, astrocytes have not traditionally been thought to be

involved in neurogenesis. " Astrocytes, so-named because of their starlike

shape, are glial cells, a term which is derived from the Latin word for

'glue,' " explained s. " They fill in the space between neurons, and

they have long been known to have a supportive role, which includes taking

up neurotransmitters released by neurons. They also maintain the

extracellular environment with the right concentrations of chemicals to

support neurons. "

Recently, however, evidence emerged that astrocytes might actually be

" instructing " stem cells about which developmental pathway to select, said

s. For example, s and his colleagues reported in a previous

research article that adult neuronal stem cells proliferated more readily

when they were cultured with astrocytes rather than on a layer of fibroblast

cells.

s said that at first it seemed likely that the astrocytes might be

keeping the stem cells alive longer or encouraging proliferation. In other

words, they might be merely supporting the cells in becoming functional

neurons, s said.

" Another possibility was that the astrocytes were somehow actually

instructing the stem cells to divide and adopt a neuronal fate, " he said.

" This seemed least likely because when the embryonic brain is growing, most

of the neurons are born before the glia, so one wouldn't have thought glia

were instructing stem cells. "

To define the astrocytes’ contribution to neuronal development, Song,

s and Gage tagged adult neural stem cells with a green fluorescent

marker so they could follow the development of those cells. When they grew

the tagged stem cells in cell culture with both astrocytes and other

neurons, the stem cells readily developed into mature neurons. However, when

the scientists grew the tagged stem cells in cultures enriched with

astrocytes, they found that the astrocytes supported the growth of many more

neurons from the stem cells.

A big question, said s, was whether the astrocytes influenced neuronal

growth by releasing chemicals or by direct contact with the stem cells. So,

the scientists cultured neural stem cells so that they could not touch the

astrocytes, or so that the astrocytes were gently killed and could not

release regulatory chemicals. The experiments showed that in both cases, the

astrocytes triggered stem cell development. This suggests that astrocytes

trigger neuronal growth both by releasing chemicals and through a

contact-related signal, s said.

Mathematical analysis of the cells in culture revealed that astrocytes

encouraged both stem cell proliferation and their maturation into neurons.

" We found that stem cells grown on glia divided about twice as fast as they

did when grown on fibroblasts, " said s. " Glia make a good environment

to instruct them to divide.

" But the big surprise was that the stem cells were adopting a neuronal fate

at about six times the rate they were on fibroblasts, " said s. " The

astrocytes either instruct the progenitors to adopt a neuronal fate or form

an environment that induces or permits that fate. We're not exactly sure

what word to use, because we don't know what the mechanism is, " he said.

In additional experiments, the researchers found that adult astrocytes were

about half as effective as embryonic astrocytes in promoting neurogenesis in

adult neural stem cells.

One intriguing implication of the experiments, said s, is that

astrocytes’ involvement in neuronal growth regulation might explain why

neural stem cells can regenerate neurons in areas of the brain such as the

hippocampus, but not in the spinal cord, where they mature into glial cells.

" It was surprising to us that the stained stem cells from the hippocampus

would only produce neurons when grown on glia from the hippocampus, but they

hardly made any neurons at all when we grew them on glia from the spinal

cord, " said s.

" While it is only speculation at this point, it may be that spinal cords

fail to regenerate not because the stem cells aren't there, but because

there is something missing in their glial cells. Thus, developing spinal

cord regeneration therapies might mean supplying some factor produced by

glial cells, " said s.

Editor's Note: The original news release can be found at

http://www.hhmi.org/news/stevens2.html

Glia 2001 Nov;36(2):180-90 Related Articles, Books, LinkOut

Immune function of astrocytes.

Dong Y, Benveniste EN.

Department of Cell Biology, University of Alabama at Birmingham, Birmingham,

Alabama 35294-0005, USA.

Astrocytes are the major glial cell within the central nervous system (CNS)

and have a number of important physiological properties related to CNS

homeostasis. The aspect of astrocyte biology addressed in this review

article is the astrocyte as an immunocompetent cell within the brain. The

capacity of astrocytes to express class II major histocompatibility complex

(MHC) antigens and costimulatory molecules (B7 and CD40) that are critical

for antigen presentation and T-cell activation are discussed. The functional

role of astrocytes as immune effector cells and how this may influence

aspects of inflammation and immune reactivity within the brain follows,

emphasizing the involvement of astrocytes in promoting Th2 responses. The

ability of astrocytes to produce a wide array of chemokines and cytokines is

discussed, with an emphasis on the immunological properties of these

mediators. The significance of astrocytic antigen presentation and

chemokine/cytokine production to neurological diseases with an immunological

component is described. Copyright 2001 Wiley-Liss, Inc.

Publication Types:

Review

Review, Academic

PMID: 11596126 [PubMed - indexed for MEDLINE]

Glia 2001 Nov;36(2):145-55 Related Articles, Books, LinkOut

Glial cell influence on the human blood-brain barrier.

Prat A, Biernacki K, Wosik K, Antel JP.

Neuroimmunology unit, Montreal Neurological Institute, McGill University,

Montreal, Quebec, Canada. aprat@...

The blood-brain barrier (BBB) is a specialized structure of the central

nervous system (CNS) that restricts immune cell migration and soluble

molecule diffusion from the systemic compartment into the CNS. Astrocytes

and microglia are resident cells of the CNS that contribute to the formation

of the BBB. In this article, we consider the influence of these glial cells

on the immune regulatory functions of the microvascular endothelium, with

special emphasis on the human BBB. A series of in vitro studies demonstrate

that soluble factors produced by glial cells, under basal culture

conditions, help restrict development of inflammation within the CNS. These

soluble factor effects include upregulating expression of molecules

including HT7, UEA-1 lectin-binding sites, and angiotensin receptors that

help define the phenotype of endothelial cells. These factors also induce

tight junction formation between brain endothelial cells, contributing to

the restricted permeability of the BBB. In contrast, these factors have

little effect on expression of molecules by ECs that either promote

lymphocyte migration, such as chemokines and adhesion molecules or molecules

that are required for competent antigen presentation, such as MHC and

co-stimulatory molecules. Glial cells that become activated in response to

signals derived from the immune system or generated within the CNS, produce

an array of inflammatory molecules that increase permeability and promote

lymphocyte trafficking and persistence. These observations emphasize the

bidirectional nature of neural-immune interactions; this dynamic system

should be amenable to therapeutic interventions. Copyright 2001 Wiley-Liss,

Inc.

Publication Types:

Review

Review, Academic

PMID: 11596123 [PubMed - indexed for MEDLINE]

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