The role of activity-dependent neuroprotective protein in a mouse model of fetal alcohol syndrome.
OBJECTIVE
Fetal alcohol syndrome (FAS) is the most common nongenetic cause of mental retardation. Peptides NAPVSIPQ (NAP) and SALLRSIPA (SAL), related to activity-dependent neuroprotective protein (ADNP), prevent alcohol-induced damage in a mouse model of FAS. Our objective was to characterize ADNP in this model to relate this protein to the mechanisms of damage and peptide neuroprotection.


METHODS
Timed, pregnant C57Bl6/J mice were treated on day 8. Groups were control, alcohol, peptide pretreatment, or peptide alone. Embryo and decidua were harvested at 6 and 24 hours and 10 days. To evaluate ADNP expression, real-time polymerase chain reaction was performed with results presented as the ratio of ADNP-to-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) concentration. Analysis of variance was performed for overall comparisons with P<.05 considered significant.


RESULTS
At 6 hours, there was no difference in ADNP between alcohol-exposed embryos compared with control embryos. At 24 hours, there was an increase in ADNP in alcohol-exposed embryos compared with controls (P<.001); these findings persisted at 10 days (P<.001). In the decidua at 6 hours, there was no difference between alcohol and control. At 24 hours, there was greater ADNP in alcohol-exposed decidua compared with controls (P<.001), which did not persist at 10 days (P=.97). Peptide pretreatment did not prevent the alcohol-induced increase in ADNP in embryo or decidua.


CONCLUSIONS
Alcohol increased embryonic and decidual ADNP expression at 24 hours and it persisted in the embryo for 10 days. Because ADNP is a known neuroprotectant, these findings suggest that it may be released as a protective mechanism in FAS. Changes in the embryo were persistent suggesting that the embryo is more vulnerable to alcohol-induced damage than the mother.
Poggi
Sarah H
SH
Department of Obstetrics and Gynecology, Georgetown University Hospital, Washington, DC, USA. shp2@gunet.georgetown.edu
Goodwin
Katie
K
Hill
Joanna M
JM
Brenneman
Douglas E
DE
Tendi
Elizabetta
E
Schinelli
Sergio
S
Abebe
Daniel
D
Spong
Catherine Y
CY
D000818:Animals; D003656:Decidua / Q000737:chemistry; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000737:chemistry; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D018398:Homeodomain Proteins / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
C117632:Adnp protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000431:Ethanol; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases