Prevention of the alcohol-induced changes in brain-derived neurotrophic factor expression using neuroprotective peptides in a model of fetal alcohol syndrome.
OBJECTIVE
Our objective was to evaluate whether brain-derived neurotrophic factor (BDNF) expression is affected by prenatal alcohol exposure and whether the neuroprotective effects of the vasoactive intestinal peptide (VIP)-related peptides, NAPVSIPQ (NAP) and SALLRSIPA (SAL), are mediated through BDNF.


METHODS
Using a well-characterized fetal alcohol syndrome (FAS) model, timed pregnant C57BL6/J mice were treated on gestational day (E) 8 with alcohol (0.03 mL/g), placebo, or alcohol plus (NAP plus SAL). Embryos were harvested at 6 hours (E8), 24 hours (E9), and 10 days (E18) and pups at postnatal day 40. Calibrator-normalized relative real time polymerase chain reaction was performed to quantify BDNF with hypoxanthine phosphoribosyl transferase-1 standardization.


RESULTS
BDNF expression was lower in the alcohol-exposed embryos than in controls at 6 hours and higher at 24 hours and 10 days (all P<.05). Pretreatment with NAP plus SAL prevented the alcohol-induced rise in BDNF expression (P<.05) at 24 hours and 10 days after alcohol exposure. We found no difference between alcohol and control in young-adults' brain (P>.05).


CONCLUSIONS
NAP plus SAL treatment prevented alcohol-induced changes in BDNF expression 24 hours and 10 days after alcohol exposure in mouse embryos. This may explain, at least in part, the peptides' prevention of neurodevelopmental anomalies in FAS.
Incerti
Maddalena
M
Unit on Perinatal and Developmental Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, Bethesda, MD, USA.
Vink
Joy
J
Roberson
Robin
R
Benassou
Ines
I
Abebe
Daniel
D
Spong
Catherine Y
CY
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy
D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D009842:Oligopeptides; C502410:seryl-alanyl-leucy-leucyl-arginyl-seryl-isoleucyl-prolyl-alanine; C425904:davunetide