PMID- 10689198
OWN - NLM
STAT- MEDLINE
DCOM- 20000421
LR  - 20191024
IS  - 0890-6238 (Print)
IS  - 0890-6238 (Linking)
VI  - 14
IP  - 1
DP  - 2000 Jan-Feb
TI  - Valproic acid-induced alterations in growth and neurotrophic factor gene 
      expression in murine embryos [corrected].
PG  - 1-11
AB  - Although the teratogenicity of valproic acid (VPA) has been well established, the 
      mechanism(s) by which this anticonvulsant drug induces malformations remains 
      controversial. Using the combined molecular techniques of in situ-transcription 
      (IST) and antisense RNA (aRNA) amplification we analyzed VPA-induced alterations 
      in the gene expression for 10 genes within the neural tubes of embryos from two 
      murine strains that have been shown to differ in their susceptibility to 
      VPA-induce neural tube defects (NTD). Pregnant dams from both SWV (susceptible) 
      and LM/Bc (resistant) strains were either treated with saline (control) or VPA 
      (600 mg/kg) on gestational day (GD) 8:12 (day:hour). Neural tubes were isolated 
      from control or VPA exposed embryos at three gestational time points, which 
      represented the beginning (GD 8:18), middle (GD 9:00), and end (GD 9:12) of 
      neural tube closure (NTC) in both of these murine strains. Using univariant 
      statistics we demonstrated that in LM/Bc embryos with NTDs, the expression of 
      bdnf, ngf, and trk, ngf-R were significantly elevated at all three time points, 
      and the cytokine, cntf was significantly decreased at GD 9:00. In contrast, the 
      major gene alterations observed in SWV embryos were a significant increase in 
      tfgalpha and tgfbeta1-3 at GD 9:00. In an effort to better define the more 
      intricate interactions between VPA exposure and the expression of these genes, we 
      analyzed our data using Principal Component Analysis. The results from this 
      analysis demonstrated that embryos from these two stains behaved differently, not 
      only in response to a VPA exposure, but also under control conditions, which may 
      explain the multifactorial nature of NTDs in these mice.
FAU - Bennett, G D
AU  - Bennett GD
AD  - Department of Veterinary Anatomy and Public Health, Texas A&M University, College 
      Station, TX 77843, USA.
FAU - Wlodarczyk, B
AU  - Wlodarczyk B
FAU - Calvin, J A
AU  - Calvin JA
FAU - Craig, J C
AU  - Craig JC
FAU - Finnell, R H
AU  - Finnell RH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Reprod Toxicol
JT  - Reproductive toxicology (Elmsford, N.Y.)
JID - 8803591
RN  - 0 (Anticonvulsants)
RN  - 0 (Growth Substances)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Teratogens)
RN  - 614OI1Z5WI (Valproic Acid)
SB  - IM
EIN - Reprod Toxicol 2000 Mar-Apr;14(2):181
MH  - Analysis of Variance
MH  - Animals
MH  - Anticonvulsants/*toxicity
MH  - Female
MH  - Gene Expression/drug effects
MH  - Gene Expression Regulation, Developmental/*drug effects
MH  - Growth Substances/biosynthesis/*genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Nerve Growth Factors/biosynthesis/*genetics
MH  - Neural Tube Defects/*chemically induced/genetics/metabolism
MH  - Pregnancy
MH  - Teratogens/*toxicity
MH  - Transcription, Genetic/drug effects
MH  - Valproic Acid/*toxicity
EDAT- 2000/02/26 09:00
MHDA- 2000/04/29 09:00
CRDT- 2000/02/26 09:00
PHST- 2000/02/26 09:00 [pubmed]
PHST- 2000/04/29 09:00 [medline]
PHST- 2000/02/26 09:00 [entrez]
AID - S0890623899000647 [pii]
AID - 10.1016/s0890-6238(99)00064-7 [doi]
PST - ppublish
SO  - Reprod Toxicol. 2000 Jan-Feb;14(1):1-11. doi: 10.1016/s0890-6238(99)00064-7.