Quantitative studies on proliferative changes of reactive astrocytes in mouse cerebral cortex

Miyake, Toshihiko; Hattori, Takanori; Fukuda, M; Kitamura, Tadahisa; Fujita, Setsuya

doi:10.1016/0006-8993(88)90757-3

Cited by 153 publications

(89 citation statements)

References 17 publications

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“…8 A,B, arrowheads), similar to GFAP-positive reactive astrocytes. This was consistent with previous studies showing the occurrence of cell division among GFAP-expressing astrocytes induced by brain injury (Miyake et al, 1988(Miyake et al, , 1992. In addition, the colocalization of BrdU and m-Msi-1 was observed in a few cells that were Ͼ100 m away from the injury site.…”

Section: Changes In M-msi-1 Immunoreactivity After Injurysupporting

confidence: 93%

“…Experimentally induced damage to the CNS leads to multiple changes in the glial cells surrounding the damaged tissue and to formation of a glial scar at the site of injury. Immunohistochemical and autoradiographic studies have indicated that hypertrophic and hyperplastic reactive astrocytes in the regions immediately adjacent to the injury site display increased levels of GFAP and become mitotically active (Miyake et al, 1988(Miyake et al, , 1992Takamiya et al, 1988).…”

Section: Changes In M-msi-1 Immunoreactivity After Injurymentioning

confidence: 99%

“…To determine whether this increased population of m-Msi-1-positive cells represents a so-called reactive astrocyte that proliferates in an injured area and participates in a glial scar formation at the site of injury (Miyake et al, 1988(Miyake et al, , 1992, we performed double-label immunostaining for m-Msi-1 and GFAP. As shown in Figure 8, in areas immediately adjacent to the injury site, numerous GFAP-positive astrocytes were present that had long and wav y processes extending in all directions or parallel to the needle track and seemed to form a thick bundle of glial array in the scar tissue, characteristics typical of reactive astrocytes.…”

Section: Changes In M-msi-1 Immunoreactivity After Injurymentioning

confidence: 99%

“…After brain injury, upregulation of m-Msi-1 expression was observed in a vast number of cells in broad regions of the injured cerebral hemisphere, including the subependyma distant from the injury site, as well as in the GFAP-positive proliferating reactive astrocytes in the immediate vicinity of the lesioned site. Previous studies suggested that protoplasmic astrocytes can transform into the fibrous type in response to injury and that the marked increase in the number of GFAP-positive reactive astrocytes in the injured cortex is principally attributable to upregulation of GFAP expression in already existing protoplasmic astrocytes surrounding the injury site, rather than to the induction of proliferation of GFAP-positive reactive astrocytes themselves (Bignami and Dahl, 1976;Graeber and Kreutzberg, 1986;Miyake et al, 1988Miyake et al, , 1992. Consistent with the presumptive m-Msi-1 expression in the protoplasmic astrocytes in the normal cerebral cortex, the majority of m-Msi-1-positive cells observed at least in the vicinity of the lesioned site may represent overproduced protoplasmic astrocytes that are destined to become reactive astrocytes in the injured area.…”

Section: Changes In M-msi-1 Immunoreactivity After Injurymentioning

confidence: 99%

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Expression of Neural RNA-Binding Proteins in the Postnatal CNS: Implications of Their Roles in Neuronal and Glial Cell Development

1997

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There is an increasing interest in the role of RNA-binding proteins during neural development. Mouse-Musashi-1 (m-Msi-1) is a mouse neural RNA-binding protein with sequence similarity to Drosophila musashi (d-msi), which is essential for neural development. m-Msi-1 is highly enriched in neural precursor cells that are capable of generating both neurons and glia during embryonic CNS development. The present study characterized m-Msi-1-expressing cells in the postnatal and adult CNS. Postnatally, m-Msi-1 was expressed in proliferative neuronal precursors in the external granule cell layer of the cerebellum and in the anterior corner of the subventricular zone of the lateral ventricles. In gliogenesis, the persistent expression of m-Msi-1 was observed in cells of the astrocyte lineage ranging from proliferative glial precursors in the subventricular zone (SVZ) to differentiated astrocytes in the parenchyma. In addition, we showed that m-Msi-1 was still expressed in proliferating cells in the adult SVZ, which may contain neural precursor or stem cells. Another neural RNA-binding protein Hu (the mammalian homolog of a Drosophila neuronal RNAbinding protein Elav) was present in postmitotic neurons throughout the development of the CNS, and its pattern of expression was compared with that of m-Msi-1. These observations imply that these two RNA-binding proteins may be involved in the development of neurons and glia by regulating gene expression at the post-transcriptional level. Key words: RNA-binding proteins; postnatal CNS; mouseMusashi-1 (m-Msi-1); Hu; Drosophila musashi; neuronal and glial precursor cells; astrocyte lineageA number of transcription factors that f unction in the proliferation and differentiation of neural precursor cells have been identified. However, the recent discovery of neural-specific RNAbinding proteins raises the possibility that the development of neural cells from the precursors may also be regulated at the post-transcriptional level. We believe that at least two gene families are represented by the neural RNA-binding proteins found in both invertebrates and vertebrates (Okano, 1995;Sakakibara et al., 1996). One, the Elav family, includes Drosophila elav genes (Yao et al., 1993) and their mammalian homologs, the Hu genes (Szabo et al., 1991). Members of this family share extensive sequence similarity with one another, and they seem to be expressed mainly in postmitotic neurons (Okano and Darnell, 1997). The other Msi family is composed of Drosophila musashi (Nakamura et al., 1994), Xenopus laevis nrp-1 (Richter et al., 1990), and their mouse homolog mouse-musashi-1 (m-msi-1) (Sakakibara et al., 1996). d-Msi is required for the two successive asymmetric cell divisions of sensory organ precursors (Nakamura et al., 1994). In contrast to the Elav family, the members of the Msi family are expressed in the neural precursor cells at least during embryonic C NS development (Sakakibara et al., 1996). Although the molecular f unctions and the in vivo RNA targets of Msi and Elav families remain largel...

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Section: Changes In M-msi-1 Immunoreactivity After Injurysupporting

confidence: 93%

Section: Changes In M-msi-1 Immunoreactivity After Injurymentioning

confidence: 99%

Section: Changes In M-msi-1 Immunoreactivity After Injurymentioning

confidence: 99%

Section: Changes In M-msi-1 Immunoreactivity After Injurymentioning

confidence: 99%

See 2 more Smart Citations

Expression of Neural RNA-Binding Proteins in the Postnatal CNS: Implications of Their Roles in Neuronal and Glial Cell Development

1997

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“…Astrocytes react to brain injury by hypertrophy of their somata and processes (5), increased synthesis of glial-fibrillary acidic protein (GFAP), or reexpression of the progenitor markers vimentin and nestin (2,6). Because a subpopulation of these reactive GFAP ϩ cells also divides (2,(6)(7)(8) it has been suggested that these cells arise from endogenous progenitors present in the adult brain (3,4,8,9). Discovering the cellular origin of this reaction to brain injury not only is crucial to design manipulations toward a better repair (10) but also has broader relevance for our concept of mature cell types in the mammalian brain.…”

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confidence: 99%

Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain

Buffo

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Tripathi

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

699

718

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Reactive gliosis is the universal reaction to brain injury, but the precise origin and subsequent fate of the glial cells reacting to injury are unknown. Astrocytes react to injury by hypertrophy and up-regulation of the glial-fibrillary acidic protein (GFAP). Whereas mature astrocytes do not normally divide, a subpopulation of the reactive GFAP ؉ cells does so, prompting the question of whether the proliferating GFAP ؉ cells arise from endogenous glial progenitors or from mature astrocytes that start to proliferate in response to brain injury. Here we show by genetic fate mapping and cell type-specific viral targeting that quiescent astrocytes start to proliferate after stab wound injury and contribute to the reactive gliosis and proliferating GFAP ؉ cells. These proliferating astrocytes remain within their lineage in vivo, while a more favorable environment in vitro revealed their multipotency and capacity for self-renewal. Conversely, progenitors present in the adult mouse cerebral cortex labeled by NG2 or the receptor for the plateletderived growth factor (PDGFR␣) did not form neurospheres after (or before) brain injury. Taken together, the first fate-mapping analysis of astrocytes in the adult mouse cerebral cortex shows that some astrocytes acquire stem cell properties after injury and hence may provide a promising cell type to initiate repair after brain injury.astrocytes ͉ cell fate ͉ cerebral cortex ͉ stem cells

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Concurrent loss and proliferation of astrocytes following lateral fluid percussion brain injury in the adult rat

et al. 1999

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Astrocyte populations were analyzed over a period of 1 month in the hippocampus following lateral fluid percussion (FP) brain injury. Rats (n = 23) were subjected either to a brain injury of moderate severity, or to anesthesia and surgery without injury (n = 7). At 3 days, 1, 2, or 4 weeks postinjury, subgroups of animals were sacrificed and the brains removed and sectioned for histochemical analysis. The density of astrocytes, identified with gold sublimate staining, decreased significantly in the ipsilateral hippocampus of injured rats 3 days following injury, eventually falling to 64% of the total astrocyte population present in uninjured animals by 1 week postinjury. One month postinjury, the density of hippocampal astrocytes had returned to 85% of the total number of astrocytes observed in the hippocampus of uninjured animals. In order to characterize the post-traumatic formation of new astrocytes, immunohistochemistry was performed using antibodies to proliferating cell nuclear antigen (PCNA) and to glial fibriallary acidic protein (GFAP). Positive immunolabeling for both PCNA and GFAP was most abundant at 3 days following FP brain injury in regions where the blood brain barrier was compromised, and was not detectable by 1 month postinjury. These results indicate that astrocyte proliferation after injury may be evoked by mitogens released from vascular sources, and may be an attempt to compensate for some of the astrocytic cell loss observed after injury.

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Quantitative studies on proliferative changes of reactive astrocytes in mouse cerebral cortex

Cited by 153 publications

References 17 publications

Expression of Neural RNA-Binding Proteins in the Postnatal CNS: Implications of Their Roles in Neuronal and Glial Cell Development

Expression of Neural RNA-Binding Proteins in the Postnatal CNS: Implications of Their Roles in Neuronal and Glial Cell Development

Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain

Concurrent loss and proliferation of astrocytes following lateral fluid percussion brain injury in the adult rat

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