Down regulation of myelin-specific mRNAs in the mechanism of hypomyelination in the undernourished developing brain.
The expression of myelin-specific protein genes, i.e. myelin proteolipid (PLP), basic (BP), and myelin associated glycoproteins (MAG) was studied in normal and severely undernourished 20-day-old rats. The undernutrition paradigm resulted in reductions of approximately 50, 25 and 65% in body weight, brain weight and brain myelin yield, respectively. The amount of total brain RNA was not significantly altered, although the amount of cyclophilin (CYC) mRNA was increased. In contrast, the steady-state levels of myelin specific mRNAs were significantly decreased by approximately 40, 20 and 40% for PLP, BP and MAG, respectively. In addition, polyadenylation of the PLP transcript was altered, producing an abnormal ratio of the 1.6 kb to the 3.2 kb PLP mRNAs. The results indicate that down-regulation of myelin-specific gene expression is involved in the mechanisms of hypomyelination in hunger disease, although the individual genes are differently altered. Furthermore, undernutrition may have additional effects on the posttranscriptional processing of the transcripts as indicated by the abnormal size distribution of PLP messages.
Royland
J
J
Department of Anatomy, School of Medicine, West Virginia University, Morgantown 26506.
Konat
G W
GW
Kanoh
M
M
Wiggins
R C
RC
D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight; D001921:Brain / Q000254:growth & development / Q000503:physiopathology*; D015342:DNA Probes; D003711:Demyelinating Diseases / Q000209:etiology / Q000503:physiopathology*; D015536:Down-Regulation; D005260:Female; D004676:Myelin Basic Protein / Q000096:biosynthesis / Q000235:genetics; D009185:Myelin Proteins / Q000096:biosynthesis* / Q000235:genetics; D018991:Myelin Proteolipid Protein; D009186:Myelin Sheath / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein; D009693:Nucleic Acid Hybridization; D009748:Nutrition Disorders / Q000150:complications / Q000503:physiopathology*; D009929:Organ Size; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats
D015342:DNA Probes; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D012333:RNA, Messenger