Hyperglycemia delays rostral initiation sites during neural tube closure.
Neural tube defects contribute greatly to perinatal loss, physical handicap, mental retardation and other developmental defects, yet the mechanisms through which they occur are poorly understood. One hindrance to the study of these defects at the cellular and molecular levels is the low frequency with which they arise in susceptible animals. The present study utilizes a culture system for the study of rodent exencephaly, an animal model of human anencephaly, in which a high frequency of affected animals are obtained by culture in hyperglycemic rat serum. Rat embryos were dissected at day 9.5 from timed-pregnant Sprague-Dawley dams and cultured under standard conditions developed by New [Biol. Rev. (1978) 53,81-122]. Embryos cultured under elevated glucose conditions are able to close the caudal neural tube with the failure of neural tube closure limited to the rostral neuralepithelium. In this report we present the novel finding that, although at the end of culture frequently only the hindbrain region remains open, the normal sequence of events expected during rostral closure anterior to the hindbrain is markedly delayed. In embryos cultured in hyperglycemic serum, both rostral initiation sites II and III are significantly delayed. The degree of delay increases with increasing glucose concentration in the culture medium. These studies support the use of this defined in vitro model of anencephaly for studies of the molecular and cellular bases underlying the failure of hindbrain closure and demonstrate that sufficient numbers of affected animals can be produced to obtain significant results.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Biochemistry and Molecular Biology, R.L. Smith Mental Retardation Research Center, University of Kansas Medical Center, Kansas City 66160-7421.
Y
Y
Peng
B E
BE
Finley
K
K
Fechtel
D000757:Anencephaly / Q000473:pathology; D000818:Animals; D004622:Embryo, Mammalian / Q000502:physiology; D005260:Female; D005947:Glucose / Q000502:physiology; D006943:Hyperglycemia / Q000473:pathology*; D008855:Microscopy, Electron, Scanning; D009436:Neural Tube Defects / Q000473:pathology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000196:embryology / Q000473:pathology
D005947:Glucose