title: Downregulation of dopamine D₁ receptors and increased neuronal apoptosis upon ethanol and PTZ exposure in prenatal rat cortical and hippocampal neurons.
abstract: The objective of this study was to evaluate the effect of ethanol and pentylenetetrazol (PTZ) on the expression of dopamine receptors (D1R) and to observe the apoptotic neurodegeneration in prenatal rat cortical and hippocampal neurons at gestational days (GD) 17.5. In the present study, ethanol (100 mM) and PTZ (15 mM) were exposed to the prenatal rat cortical and hippocampal neuronal cell cultures for 1 h. For mRNA RT-PCR and for protein Western blot analysis was done to elucidate D1R, Bax, Bak, Bcl-2 and cleaved caspase-3 expression upon ethanol and PTZ exposure in neuronal cell cultures. Furthermore, ethanol and PTZ-induced apoptotic neurodegeneration was also observed using TUNEL staining and propidium iodide (PI) used as counter stain under confocal microscopy. The results of present study showed that ethanol and PTZ exposure significantly decreased D1R expression and induced neuronal death by significantly increasing the expression of pro-apoptotic Bax, Bak and decreasing anti-apoptotic protein Bcl-2 leading to the apoptosis by increasing cleaved caspase-3 expression in cortical and hippocampal primary neuronal cell cultures. Our findings indicated that ethanol and PTZ exposure to the prenatal neurons showed not only downregulation of D1R but also causes neuronal apoptosis in the developing rat brain. Further, this explains the possibility of higher risk of developmental disturbances and malformations during early developmental stage.
authors.affiliation: Center of Excellence in Genomic Medicine and Research (CEGMR), King Abdulaziz University, Jeddah, 21589, Saudi Arabia, mimrannaseer@yahoo.com.
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Naseer
authors.forename: Ikram
authors.initials: I
authors.lastname: Ullah
authors.forename: Mahmood
authors.initials: M
authors.lastname: Rasool
authors.forename: Shakeel Ahmed
authors.initials: SA
authors.lastname: Ansari
authors.forename: Ishfaq Ahmed
authors.initials: IA
authors.lastname: Sheikh
authors.forename: Fehmida
authors.initials: F
authors.lastname: Bibi
authors.forename: Adeel Gulzar
authors.initials: AG
authors.lastname: Chaudhary
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Al-Qahtani
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003292:Convulsants / Q000633:toxicity; D015536:Down-Regulation; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010433:Pentylenetetrazole / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D003292:Convulsants; D017447:Receptors, Dopamine D1; D000431:Ethanol; D010433:Pentylenetetrazole