Recovery of adult oligodendrocytes is preceded by a "lag period" accompanied by upregulation of transcription factors expressed in developing young cells.
Cell cultures prepared from oligodendrocytes directly obtained from adult rat brain are composed of mature cells that lose their cell processes and myelin membrane during their isolation and therefore represent a very useful model to investigate the factors that could stimulate their recovery. We have observed that mature oligodendrocytes isolated from adult animals remain as round cells that lack processes for the first 3-4 days in culture. At the end of this lag period, however, the majority of the adult oligodendrocytes show a remarkable recovery, rapidly growing complex and extensive cell processes. Interestingly, the end of this lag period is accompanied by a dramatic upregulation in the expression of thyroid hormone (T(3)) receptor (TR). The functional importance of this increase in TR levels is supported by the observation that the majority of the cells cultured in the presence of T(3) show significantly more extensive and complex process outgrowth than the control cells in cultures lacking this hormone. In addition, this reactivation of the adult cells was also preceded by an increased expression of glucocorticoid receptor (GR) and cyclic AMP-response element binding protein (CREB), two transcription factors that together with TR appear to play important roles in the control of neonatal oligodendrocyte development. Thus, it is possible to hypothesize that upregulation of these proteins may be part of the metabolic changes that occur during the lag period required for recovery of the adult oligodendrocytes. These observations raise the question of whether these transcription factors may play any significant role during remyelination after demyelinating lesions of adult CNS.
Afshari
Fatemah S
FS
Department of Biochemistry and Molecular Biophysics, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298-0614, USA.
Chu
Annie K
AK
Sato-Bigbee
Carmen
C
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D003711:Demyelinating Diseases / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D004676:Myelin Basic Protein / Q000187:drug effects / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D004676:Myelin Basic Protein; D011965:Receptors, Glucocorticoid; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; D014284:Triiodothyronine