Differential Early Mechanistic Frontal Lobe Responses to Choline Chloride and Soy Isoflavones in an Experimental Model of Fetal Alcohol Spectrum Disorder.
Fetal alcohol spectrum disorder (FASD) is the most common preventable cause of neurodevelopmental defects, and white matter is a major target of ethanol neurotoxicity. Therapeutic interventions with choline or dietary soy could potentially supplement public health preventive measures. However, since soy contains abundant choline, it would be important to know if its benefits are mediated by choline or isoflavones. We compared early mechanistic responses to choline and the Daidzein+Genistein (D+G) soy isoflavones in an FASD model using frontal lobe tissue to assess oligodendrocyte function and Akt-mTOR signaling. Long Evans rat pups were binge administered 2 g/Kg of ethanol or saline (control) on postnatal days P3 and P5. P7 frontal lobe slice cultures were treated with vehicle (Veh), Choline chloride (Chol; 75 µM), or D+G (1 µM each) for 72 h without further ethanol exposures. The expression levels of myelin oligodendrocyte proteins and stress-related molecules were measured by duplex enzyme-linked immunosorbent assays (ELISAs), and mTOR signaling proteins and phosphoproteins were assessed using 11-plex magnetic bead-based ELISAs. Ethanol's main short-term effects in Veh-treated cultures were to increase GFAP and relative PTEN phosphorylation and reduce Akt phosphorylation. Chol and D+G significantly modulated the expression of oligodendrocyte myelin proteins and mediators of insulin/IGF-1-Akt-mTOR signaling in both control and ethanol-exposed cultures. In general, the responses were more robust with D+G; the main exception was that RPS6 phosphorylation was significantly increased by Chol and not D+G. The findings suggest that dietary soy, with the benefits of providing complete nutrition together with Choline, could be used to help optimize neurodevelopment in humans at risk for FASD.
Pubmed ID: 37108779 RIS Download
Research resources used in this publication
None foundAdditional research tools detected in this publication
Antibodies used in this publication
- Goat Anti-4 Hydroxynonenal Polyclonal Antibody, Unconjugated (RRID:AB_722493)
- Mouse Anti-8-Hydroxy-2'-deoxyguanosine Monoclonal Antibody, Unconjugated, Clone N45.1 (RRID:AB_867461)
- Myelin PLP antibody (RRID:AB_776593)
- Rabbit Anti-Ubiquitin Polyclonal Antibody, Unconjugated (RRID:AB_306069)
- GFAP Monoclonal Antibody (131-17719) (RRID:AB_2535827)
- PDGF Receptor alpha antibody (RRID:AB_2162341)
- Rabbit Anti-Galactosylceramidase Polyclonal Antibody, Unconjugated (RRID:AB_2108528)
- Anti-Myelin Basic Protein (MBP) antibody produced in rabbit (RRID:AB_1841021)
- Myelin oligodendrocyte glycoprotein antibody (RRID:AB_2145529)
- Mouse Anti-Human MAG Monoclonal Antibody, Unconjugated (RRID:AB_2042411)
Associated grants
- Agency: NIAAA NIH HHS, United States
Id: R01-AA011431 - Agency: NIAAA NIH HHS, United States
Id: R01-AA028408
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This is a list of tools and resources that we have found mentioned in this publication.
Thermo Fisher Scientific (tool)
RRID:SCR_008452
Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsCrl:LE (tool)
RRID:RGD_2308852
Rattus norvegicus with name Crl:LE from RGD.
View all literature mentionsGoat Anti-4 Hydroxynonenal Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_722493
This polyclonal targets 4 Hydroxynonenal
View all literature mentionsMouse Anti-8-Hydroxy-2'-deoxyguanosine Monoclonal Antibody, Unconjugated, Clone N45.1 (antibody)
RRID:AB_867461
This monoclonal targets 8-Hydroxy-2'-deoxyguanosine
View all literature mentionsMyelin PLP antibody (antibody)
RRID:AB_776593
This polyclonal targets Myelin PLP antibody
View all literature mentionsRabbit Anti-Ubiquitin Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_306069
This polyclonal targets Ubiquitin
View all literature mentionsGFAP Monoclonal Antibody (131-17719) (antibody)
RRID:AB_2535827
This monoclonal targets GFAP
View all literature mentionsPDGF Receptor alpha antibody (antibody)
RRID:AB_2162341
This polyclonal targets PDGF Receptor alpha
View all literature mentionsRabbit Anti-Galactosylceramidase Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_2108528
This polyclonal targets Galactosylceramidase
View all literature mentionsAnti-Myelin Basic Protein (MBP) antibody produced in rabbit (antibody)
RRID:AB_1841021
This unknown targets Myelin Basic Protein (MBP)
View all literature mentionsMyelin oligodendrocyte glycoprotein antibody (antibody)
RRID:AB_2145529
This polyclonal targets Myelin oligodendrocyte glycoprotein
View all literature mentionsMouse Anti-Human MAG Monoclonal Antibody, Unconjugated (antibody)
RRID:AB_2042411
This monoclonal targets Human MAG
View all literature mentions
