Transcriptional Regulation Studies of Myelin-Associated Genes in &lt;i&gt;Myelin-Deficient&lt;/i&gt;Mutant Rats

Kumar, Sumit; Macklin, Wendy B.; Gordon, Marcia N.; Monteros, Alejandro Espinosa de los; Cole, R.; Scully, Sheila; Vellis, Jean de

doi:10.1159/000111860

Cited by 30 publications

(23 citation statements)

References 28 publications

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“…However, elongated nestin+ cell processes were present in the subventricular region of untreated md animals at the same age. This extended expression of nestin in the subventricular regions of the untreated md rat brain confi rms the immature status of the md CNS [8] .…”

Section: Discussionsupporting

confidence: 57%

“…Myelin loss has devastating effects in patients affl icted by multiple sclerosis or Pelizaeus-Merzbacher disease. Previously, using the myelin-defi cient mutant rat (md) we showed that failure of OLs to mature is the cause of myelin defi ciency [7][8][9] . We also showed that in cell culture md OL progenitors (OLPs) express markers that are synthesized by more mature OL; however, these were not expressed in vivo [7,10] , suggesting that an adequate trophic environment might result in further maturation of OLs in these mutants.…”

Section: Introductionmentioning

confidence: 99%

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Activation, Proliferation and Commitment of Endogenous Stem/Progenitor Cells to the Oligodendrocyte Lineage by TS1 in a Rat Model of Dysmyelination

Espinosa‐Jeffrey

Zhao²,

Awosika³

et al. 2006

Dev Neurosci

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Wild-type and myelin-deficient rats received a single intraparenchymal injection of TS1, a specific combination of IGF-1 and transferrin (Tf), into their corpus callosum at postnatal day 4. The fate of endogenous stem cells in the brain was examined by the expression of the stem cell marker nestin, together with Tf, neurofilaments and glial fibrillary acidic protein from 2 to 14 days after injection. Treated mutants lacked nestin expression in the ventricular wall and had an increase in nestin-labeled radial cell processes in the subventricular regions, and extended into the parenchyma. The subventricular zone was populated by healthy new oligodendrocytes (OLs). BrdU incorporation showed that these cells originated by proliferation and were identified as OLs based upon Tf expression. Thus, TS1 is an effective treatment to promote endogenous subventricular zone progenitor proliferation, migration and OL lineage specification. This strategy offers for the first time the possibility of myelin restoration to treat myelin disorders.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Activation, Proliferation and Commitment of Endogenous Stem/Progenitor Cells to the Oligodendrocyte Lineage by TS1 in a Rat Model of Dysmyelination

Espinosa‐Jeffrey

Zhao²,

Awosika³

et al. 2006

Dev Neurosci

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“…The transcription rate of PLP is greatly reduced in m d rats [26]. Our in vitro results suggest that a recovery of PLP tran scription rate occurs under cell culture condi tions.…”

Section: Discussionmentioning

confidence: 60%

“…These findings suggest that MBP and PLP mRNA levels in vitro are increased and may be translated into protein. Since MBP transcription rate is normal in m d rats [26], the increase in MBP mRNA must result from a posttranscriptional effect that takes place in m d cultures in vitro but not in m d animals in vivo.…”

Section: Discussionmentioning

confidence: 99%

The <i>Myelin-Deficient</i>Rat Mutant: Partial Recovery of Oligodendrocyte Maturation in vitro

et al. 1990

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The morphological and immunocytochemical identification and characterization of the myelin-forming cell, the oligodendrocyte, have defined a model system for developmental studies. The myelin-defictent (md) rat mutant lacks myelin in the central nervous system and fails to express the normal developmental increase in oligodendroglial and myelin markers, apparently as a consequence of a point mutation in the proteolipid protein gene. In the present work, we compared the developmental pattern of primary glial cultures derived from newborn md rat brains to those derived from wild-type animals. Brain cell suspensions were prepared from each rat pup and cultured separately. We found by immunocytochemical and enzymatic analyses for the various markers that the developmental cascade of oligodendroglial marker expression is delayed, oligodendrocytes failing to mature compared to normal cultures. However, a partial recovery of marker expression was observed in md-derived cultures as compared to development previously reported in the intact md animals. We suggest that the partial recovery of the sequential expression of oligodendroglial markers may be due to a supportive environment provided to the oligodendrocyte progenitor cell (1) by tissue culture conditions or (2) by the absence of the blood-brain barrier in contrast to its presence in the intact animal.

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“…USA 90 (1993) antibody, a specific marker for microglia and macrophages (13). No (18) and displays an arrest in oligodendrocyte differentiation (19,20). The …”

mentioning

confidence: 99%

O2A progenitor cells transplanted into the neonatal rat brain develop into oligodendrocytes but not astrocytes.

Monteros

Zhang

Vellis

1993

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

124

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The differentiation of the bipotential 02Aprogenitor cell into an oligodendrocyte or a type 2 astrocyte has been well documented in cell cultures of various regions of the central nervous system. The appropriate tools to prove its existence in vivo have been lacking. We report on an in vitro-in vivo approach that combines stable labeling of an enriched population of cultured 02A progenitors by the fluorescent dye fast blue, followed by their transplantation into neonatal rat brains, which allowed us to study the influence of the brain microenvironment on their lineage decision. Recently, the existence of type 2 astrocytes in vivo has been questioned (6, 7). Raffand coworkers (5) have estimated the in vivo appearance of type 1 astrocytes, oligodendrocytes, and type 2 astrocytes in the rat optic nerve to be at postnatal day 0 (PO), P4, and P15, respectively. However, a light and electron microscopic immunocytochemical analysis of [3H]thymidine pulse-labeled developing rats has revealed only two periods of astrocyte and oligodendrocyte generations, the earliest being that of GFAP+ cells near PO followed by a wave of oligodendrocytes at P4-P8 (6, 7). A major obstacle to resolve this controversy has been the lack of appropriate markers to identify type 2 astrocytes in the brain (5). The antibody A2B5 is not a reliable marker in tissue sections because it stains unrelated cell types and intracellular structures (for review, see refs. 7 and 8).In this study, we propose an approach to compare the fate of 02A progenitors in the in vivo vs. in vitro environment. An enriched population of 02A progenitors in culture was labeled with the fluorescent dye fast blue (FB) and transplanted into neonatal rat brains. The phenotypic differentiation of 02A cells was studied in tissue sections by single and double immunolabeling and examined by fluorescence microscopy to visualize grafted cells and their progeny. We have reported (9) that FB-labeled cultured glial cells transplanted into normal and myelin-deficient (md) Wistar rats remain identifiable in immunostained tissue sections up to 6 months after grafting (9). We now report that transplanted 02A progenitors in vivo develop into oligodendrocytes but not astrocytes. MATERIALS AND METHODSAnimals. Normal Wistar and md Wistar rat pups were raised in our breeding colonies. Rats were housed in a restricted-access temperature-controlled vivarium on a 12-h light/12-h dark cycle, with free access to food and water. Fifty percent of pups born to previously identified female carriers of the md trait are genetically normal (+/y) and 50% carry the md trait (md/y). Males ofboth genotypes were used at P5 as recipients for cell transplants.Cell Culture. Primary cultures were prepared from newborn rat brains as described (10). These cultures were maintained in Waymouth medium supplemented with 10% (vol/ vol) fetal calf serum. After 9 days in culture, 02A cells growing on top ofthe astrocyte monolayer (type 1 astrocytes) were removed by a modification of the method of McCarthy and de Vel...

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Transcriptional Regulation Studies of Myelin-Associated Genes in <i>Myelin-Deficient</i>Mutant Rats

Cited by 30 publications

References 28 publications

Activation, Proliferation and Commitment of Endogenous Stem/Progenitor Cells to the Oligodendrocyte Lineage by TS1 in a Rat Model of Dysmyelination

Activation, Proliferation and Commitment of Endogenous Stem/Progenitor Cells to the Oligodendrocyte Lineage by TS1 in a Rat Model of Dysmyelination

The <i>Myelin-Deficient</i>Rat Mutant: Partial Recovery of Oligodendrocyte Maturation in vitro

O2A progenitor cells transplanted into the neonatal rat brain develop into oligodendrocytes but not astrocytes.

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