Taurine 8 pp 101-109 | Cite as

The Effect of Folic Acid on GABAA-B 1 Receptor Subunit

  • Kizzy VasquezEmail author
  • Salomon Kuizon
  • Mohammed Junaid
  • Abdeslem El Idrissi
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 775)


Autism contains a spectrum of behavioral and cognitive disturbances of childhood development that is manifested by deficits in social interaction, impaired communication, repetitive behavior, and/or restricted interest. Much research has been dedicated to finding the genes that are responsible for autism, but less than 10% of the cases can be attributed to one gene. Autism prevalence has increased in the last decade and there may be environmental components that are leading to this increase. There are reports of disruption of epigenetic mechanisms controlling the regulation of gene expression as probable cause for autism. Folic acid (FA) is prescribed to women during pregnancy, and can cause epigenetic changes. GABAergic pathway is involved in inhibitory neurotransmission in the central nervous system and plays a crucial role during early embryonic development. Autism may entail defect or deregulation of the GABAergic receptor pathway in the brain. Gamma-aminobutyric acid (type A) beta 1 receptor (GABRB1) disruption has been implicated in autism. In the present study, we investigated GABRB1 expression in response to FA supplementation in neuronal cells. Western blot analysis showed GABRB1 protein levels increased in the FA-treated cells in a concentration-dependent manner. FA-dependent increased expression of GABRB1 was further confirmed at the mRNA level using quantitative RT-PCR. These results suggest that epigenetic control of gene expression may affect the expression of GABRB1 and disrupt inhibitory synaptic transmission during embryonic development.


Folic Acid GABAA Receptor GABAA Receptor Subunit GABAA Receptor Complex Fmr1 Knockout Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Gamma-aminobutyric acid type A receptor beta 1 subunit


Gamma-aminobutyric acid type A receptors


Folic acid


Glutamic acid decarboxylase



This study is supported by funds from the New York State Office for People with Developmental Disabilities, The City University of New York, The College of Staten Island, and Louis Stokes Alliance for Minority Participation a division of National Science Foundation (NSF). Financial assistance to Kizzy Vasquez is gratefully acknowledged.


  1. Beard CM, Panser LA, Katusic SK (2011) Is excess folic acid supplementation a risk factor for autism? Med Hypotheses 77(1):15–17PubMedCrossRefGoogle Scholar
  2. Bekkers MB, Elstgeest LE, Scholtens S, Haveman-Nies A, de Jongste JC, Kerkhof M, Koppelman GH, Gehring U, Smit HA, Wijga AH (2012) Maternal use of folic acid supplements during pregnancy, and childhood respiratory health and atopy. Eur Respir J 39(6):1468–1474PubMedCrossRefGoogle Scholar
  3. Fatemi SH, Reutiman TJ, Folsom TD, Rooney RJ, Patel DH, Thuras PD (2010) mRNA and protein levels for GABAAalpha4, alpha5, beta1 and GABABR1 receptors are altered in brains from subjects with autism. J Autism Dev Disord 40(6):743–750PubMedCrossRefGoogle Scholar
  4. Huang ZJ, Di Cristo G, Ango F (2007) Development of GABA innervation in the cerebral and cerebellar cortices. Nat Rev Neurosci 8:673–686PubMedCrossRefGoogle Scholar
  5. Junaid MA, Kuizon S, Cardona J, Azher T, Murakami N, Pullarkat RK, Brown WT (2011) Folic acid supplementation dysregulates gene expression in lymphoblastoid cells -implications in nutrition. Biochem Biophys Res Commun 412(4):688–692PubMedCrossRefGoogle Scholar
  6. Kuizon S, DiMaiuta K, Walus M, Jenkins EC Jr, Kuizon M, Kida E, Golabek AA, Espinoza DO, Pullarkat RK, Junaid MA (2010) A critical tryptophan and Ca2+ in activation and catalysis of TPPI, the enzyme deficient in classic late-infantile neuronal ceroid lipofuscinosis. PLoS One 5(8):e11929PubMedCrossRefGoogle Scholar
  7. McLennan Y, Polussa J, Tassone F, Hagerman R (2011) Fragile x syndrome. Curr Genomics 12(3): 216–224PubMedCrossRefGoogle Scholar
  8. MMWR (1992) Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. Morb Mortal Wkly Rep 41:1–7Google Scholar
  9. Olsen RW, Sieghart W (2009) GABA A receptors: subtypes provide diversity of function and pharmacology. Neuropharmacology 56(1):141–148PubMedCrossRefGoogle Scholar
  10. Pfeiffer CM, Fazili Z, McCoy L, Zhang M, Gunter EW (2004) Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay. Clin Chem 50:423–432PubMedCrossRefGoogle Scholar
  11. U.S. Preventive Services Task Force (2009) Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 150:626–632Google Scholar
  12. Wolff T, Witkop CT, Miller T, Syed SB, U.S. Preventive Services Task Force (2009) Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 150(9):632–639PubMedGoogle Scholar
  13. Zhang A, Shen CH, Ma SY, Ke Y, El Idrissi A (2009) Altered expression of Autism-associated genes in the brain of Fragile X mouse model. Biochem Biophys Res Commun 379(4):920–923PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Kizzy Vasquez
    • 1
    • 2
    • 3
    Email author
  • Salomon Kuizon
    • 3
  • Mohammed Junaid
    • 3
  • Abdeslem El Idrissi
    • 1
    • 2
  1. 1.Department of BiologyCollege of Staten IslandStaten IslandUSA
  2. 2.City University of New York Graduate SchoolNew YorkUSA
  3. 3.Department of Structural NeurobiologyNew York State Institute for Basic ResearchStaten IslandUSA

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