Neuroprotective effect of vitamin C against the ethanol and nicotine modulation of GABAB receptor and PKA-α expression in prenatal rat brain

• Published in: Synapse (New York, N.Y.) Vol. 64; no. 6; pp. 467 - 477
• Main Authors: Naseer, M.I., Lee, H.Y., Kim, M.O.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-06-2010
• Subjects: cortex; cortex, prenatal rat; ethanol; GABAB receptors; nicotine; prenatal rat; vitamin-C
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/syn.20752

Prenatal ethanol exposure has various deleterious effects on neuronal development and can induce various defects in developing brain, resulting in fetal alcohol syndrome (FAS). γ‐Aminobutyric acid (GABAB) receptor (R) is known to play an important role during the development of the central nervous system (CNS). Our study was designed to investigate the effect of ethanol (100 mM), nicotine (50 μM) (for 30 min and 1 h), vitamin C (vitC, 0.5 mM), ethanol plus vitC, and nicotine plus vitC on expression level of GABAB1, GABAB2R, and protein kinase A‐α (PKA) in prenatal rat cortical and hippocampal neurons at gestational days (GD) 17.5. The results showed that, upon ethanol and nicotine exposure, GABAB1 and GABAB2R protein expression increased significantly in the cortex and hippocampus for a short (30 min) and long term (1 h), whereas only GABAB2R subunit was decreased upon nicotine exposure for a long term in the cortex. Furthermore, PKA expression in cortex and hippocampus increased with ethanol exposure during short term, whereas long‐term exposure results increased in cortex and decreased in hippocampus. Moreover, the cotreatment of vitC with ethanol and nicotine showed significantly decreased expression of GABAB1, GABAB2R, and PKA in cortex and hippocampus for a long‐term exposure. Mitochondrial membrane potential, Fluoro‐jade‐B, and propidium iodide staining were used to elucidate possible neurodegeneration. Our results suggest the involvement of GABABR and PKA in nicotine and ethanol‐mediated neurodevelopmental defects and the potential use of vitC as a effective protective agent for FAS‐related deficits. Synapse 64:467–477, 2010. © 2010 Wiley‐Liss, Inc.