PMID- 27162054
OWN - NLM
STAT- MEDLINE
DCOM- 20171208
LR  - 20200319
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 40
IP  - 6
DP  - 2016 Jun
TI  - Modeling Fetal Alcohol Spectrum Disorder: Validating an Ex Vivo Primary 
      Hippocampal Cell Culture System.
PG  - 1273-82
LID - 10.1111/acer.13090 [doi]
AB  - BACKGROUND: Fetal alcohol spectrum disorder (FASD) is the leading nongenetic 
      cause of mental retardation. There are no treatments for FASD to date. 
      Preclinical in vivo and in vitro studies could help in identifying novel drug 
      targets as for other diseases. Here, we describe an ex vivo model that combines 
      the physiological advantages of prenatal ethanol (EtOH) exposure in vivo with the 
      uniformity of primary fetal hippocampal culture to characterize the effects of 
      prenatal EtOH. The insulin signaling pathways are known to be involved in 
      hippocampal functions. Therefore, we compared the expression of insulin signaling 
      pathway genes between fetal hippocampi (in vivo) and primary hippocampal culture 
      (ex vivo). The similarity of prenatal EtOH effects in these 2 paradigms would 
      deem the ex vivo culture acceptable to screen possible treatments for FASD. 
      METHODS: Pregnant Sprague-Dawley rats received 1 of 3 diets: ad libitum standard 
      laboratory chow (control-C), isocaloric pair-fed (nutritional control), and EtOH 
      containing liquid diets from gestational day (GD) 8. Fetal male and female 
      hippocampi were collected either on GD21 (in vivo) or on GD18 for primary culture 
      (ex vivo). Transcript levels of Igf2, Igf2r, Insr, Grb10, Rasgrf1, and Zac1 were 
      measured by reverse transcription quantitative polymerase chain reaction. 
      RESULTS: Hippocampal transcript levels differed by prenatal treatment in both 
      males and females with sex differences observed in the expression of Igf2 and 
      Insr. The effect of prenatal EtOH on the hippocampal expression of the insulin 
      pathway genes was parallel in the in vivo and the ex vivo conditions. 
      CONCLUSIONS: The similarity of gene expression changes in response to prenatal 
      EtOH between the in vivo and the ex vivo conditions ascertains that these effects 
      are already set in the fetal hippocampus at GD18. This strengthens the 
      feasibility of the ex vivo primary hippocampal culture as a tool to test and 
      screen candidate drug targets for FASD.
CI  - Copyright (c) 2016 by the Research Society on Alcoholism.
FAU - Tunc-Ozcan, Elif
AU  - Tunc-Ozcan E
AD  - Department of Psychiatry and Behavioral Sciences, The Asher Center, Feinberg 
      School of Medicine, Northwestern University, Chicago, Illinois.
FAU - Ferreira, Adriana B
AU  - Ferreira AB
AD  - Department of Cellular and Molecular Biology, Feinberg School of Medicine, 
      Northwestern University, Chicago, Illinois.
FAU - Redei, Eva E
AU  - Redei EE
AD  - Department of Psychiatry and Behavioral Sciences, The Asher Center, Feinberg 
      School of Medicine, Northwestern University, Chicago, Illinois.
LA  - eng
GR  - R01 AA017978/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Validation Study
DEP - 20160510
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Igf2 protein, rat)
RN  - 0 (Plagl1 protein, rat)
RN  - 0 (Rasgrf1 protein, rat)
RN  - 0 (Receptors, Somatomedin)
RN  - 0 (Transcription Factors)
RN  - 0 (ras-GRF1)
RN  - 151441-47-3 (GRB10 Adaptor Protein)
RN  - 3K9958V90M (Ethanol)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Animals
MH  - Cell Cycle Proteins/biosynthesis
MH  - Ethanol/adverse effects
MH  - Female
MH  - Fetal Alcohol Spectrum Disorders/*metabolism
MH  - GRB10 Adaptor Protein/biosynthesis
MH  - Gene Expression/drug effects
MH  - *Gene Expression Profiling
MH  - Genes, Tumor Suppressor
MH  - Hippocampus/*metabolism
MH  - Insulin-Like Growth Factor II/biosynthesis
MH  - Male
MH  - Models, Biological
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/metabolism
MH  - Primary Cell Culture/*methods
MH  - Rats
MH  - Receptor, Insulin/biosynthesis
MH  - Receptors, Somatomedin/biosynthesis
MH  - Sex Characteristics
MH  - Signal Transduction/genetics
MH  - Transcription Factors/biosynthesis
MH  - ras-GRF1/biosynthesis
PMC - PMC4889522
MID - NIHMS774692
OTO - NOTNLM
OT  - Fetal
OT  - Hippocampus
OT  - Insulin Pathway Genes
OT  - Prenatal Ethanol
OT  - Primary Culture
COIS- Conflict of Interest: All authors declare no conflict of interest.
EDAT- 2016/05/11 06:00
MHDA- 2017/12/09 06:00
PMCR- 2017/06/01
CRDT- 2016/05/11 06:00
PHST- 2015/12/17 00:00 [received]
PHST- 2016/03/30 00:00 [accepted]
PHST- 2016/05/11 06:00 [entrez]
PHST- 2016/05/11 06:00 [pubmed]
PHST- 2017/12/09 06:00 [medline]
PHST- 2017/06/01 00:00 [pmc-release]
AID - 10.1111/acer.13090 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2016 Jun;40(6):1273-82. doi: 10.1111/acer.13090. Epub 2016 
      May 10.