Astrocytes: Form, Functions, and Roles in Disease

Abstract

Abstract. Astrocytes, once relegated to a mere supportive role in the central nervous system, are now recognized as a heterogeneous class of cells with many important and diverse functions. Major astrocyte functions can be grouped into three categories: guidance and support of neuronal migration during development, maintenance of the neural microenvironment, and modulation of immune reactions by serving as antigen-presenting cells. The concept of astrocytic heterogeneity is critical to understanding the functions and reactions of these cells in disease. Astrocytes from different regions of the brain have diverse biochemical characteristics and may respond in different ways to a variety of injuries. Astrocytic swelling and hypertrophy-hyperplasia are two common reactions to injury. This review covers the morphologic and pathophysiologic findings, time course, and determinants of these two responses. In addition to these common reactions, astrocytes may play a primary role in certain diseases, including epilepsy, neurological dysfunction in liver disease, neurodegenerative disorders such as Parkinson's and Huntington's diseases, and demyelination. Evidence supporting primary involvement of astrocytes in these diseases will be considered.Key words: Astrocyte; functions; morphology; pathology.Neuroglia were recognized as distinct cellular elements in the central nervous system (CNS) in the late 1 8 0 0~.~~~ Mihaly von Lenhossek in 1895 proposed the name astrocyte to identify a specific class of these cells and suggested that the term neuroglia be used to encompass all supporting cells in the CNS.256 Astrocytes have long been considered as playing structural and supporting roles, reacting sluggishly and in a largely stereotypical manner to injury and disease. Rarely have astrocytes been identified as playing a primary part in diseases of the CNS. Mainly because of advances in cell culture and more specific ways to identify these cells, knowledge of astrocytic development, form, function, and roles in disease has increased dramatically. Astrocytes are estimated to comprise as much as 20-25% or even up to 50% of the total volume in some brain a r e a~. * I .~~~ Although with increasing brain weight there is a decrease in the number of neurons across several species, in the same species the ratio of glia to neurons increases. Astrocytic density then remains relatively constant or may even increase in more phylogenetically advanced species.256 These findings indicate the importance of astrocytes in the CNS.As is true of many aspects of cell biology and medicine, knowledge gained from studies in one species may not apply to other animals or to human beings. Likewise, information from in vitro studies may not be representative of astrocytes in situ8' In an organ as biochemically and functionally complex as the brain, knowledge gained from the study of astrocytes in specific areas may not apply to other regions of the CNS. The concept of astrocytic morphologic, biochemical, and functional heterogeneity is important to remem...

Astrócitos imunorreativos à proteína glial fibrilar ácida (GFAP) em sistema nervoso central de equinos normais e de equinos com leucoencefalomalácia

“…No entanto, nem sempre se verifica aumento da quantidade de GFAP intracitoplasmático quando determinado por métodos quantitativos (Eng et al 1992). Mas o estudo de astrócitos imunorreativos fornece informações mais precisas em relação ao seu estado funcional (Montgomery 1994). A melhoria das técnicas que desmascaram os determinantes antigênicos da GFAP com uso de enzimas, microondas ou tratamento térmico apresentam novas perspectivas quanto ao estudo dos astrócitos GFAP+ (Cullen 1997).…”

“…Estudos sobre o desenvolvimento embrionário, morfologia, funções e participação de astrócitos em processos patológicos têm sido frequentes ultimamente (Montgomery 1994).…”

“…Astrócitos são importantes por fornecerem suporte nutricional e estrutural para neurônios, por participarem funcionalmente da barreira hemato-encefálica (Bignani 1991) e por participarem de outras funções propostas tais como detoxificação, fagocitose, funções imunes e outras (revisado por Montgomery 1994).…”

“…A literatura veterinária é pobre em informações sobre a participação de astrócitos na patogênese de doenças naturais do SNC que afetam as diversas espécies animais (Montgomery 1994). Assim, o presente trabalho, teve como objetivo investigar a distribuição de astrócitos imunorreativos à GFAP na substância branca da cortex cerebral de equinos normais e também de equinos com leucoencefalomalácia (LEM) causada por ingestão de alimento contaminado com micotoxina.…”

Syngeneic central nervous system transplantation of genetically transduced mature, adult astrocytes

“…Trophic factors necessary for their growth and survival are very likely fairly ubiquitous. 20,21 Thus, the mature adult astrocytes were transplanted into an environment that was naturally conducive to their survival with little adaptive adjustment required. The degree of success may also be due in part to support rendered by endogenous brain astrocytes.…”