title: Prenatal alcohol-induced neuroapoptosis in rat brain cerebral cortex: protective effect of folic acid and betaine.
abstract: OBJECTIVE
  Alcohol consumption in pregnancy may cause fetal alcohol syndrome (FAS) in the infant. This study aims to investigate prenatal alcohol exposure related neuroapoptosis on the cerebral cortex tissues of newborn rats and possible neuroprotective effects of betaine, folic acid, and combined therapy.
  
  
  METHODS
  Pregnant rats were divided into five experimental groups: control, ethanol, ethanol + betaine, ethanol + folic acid, and ethanol + betaine + folic acid combined therapy groups. We measured cytochrome c release, caspase-3, calpain and cathepsin B and L. enzyme activities. In order to observe apoptotic cells in the early stages, TUNEL method was chosen together with histologic methods such as assessing the diameters of the apoptotic cells, their distribution in unit volume and volume proportion of cortical intact neuron nuclei.
  
  
  RESULTS
  Calpain, caspase-3 activities, and cytochrome c levels were significantly increased in alcohol group while cathepsin B and L. activities were also found to be elevated albeit not statistically significant. These increases were significantly reversed by folic acid and betaine + folic acid treatments. While ethanol increased the number of apoptotic cells, this increase was prevented in ethanol + betaine and ethanol + betaine + folic acid groups. Morphometric examination showed that the mean diameter of apoptotic cells was increased with ethanol administration while this increase was reduced by betaine and betaine + folic acid treatments.
  
  
  CONCLUSIONS
  We observed that ethanol is capable of triggering apoptotic cell death in the newborn rat brains. Furthermore, folic acid, betaine, and combined therapy of these supplements may reduce neuroapoptosis related to prenatal alcohol consumption, and might be effective on preventing fetal alcohol syndrome in infants.
authors.affiliation: Vocational School of Health Services, Istanbul Bilim University, Yazarlar Sok. No:17, 34394, Istanbul, Turkey. ibrahim.sogut@gmail.com.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Sogut
authors.affiliation: Vocational School of Health Services, Eskisehir Osmangazi University, 26480, Eskisehir, Turkey.
authors.forename: Onur
authors.initials: O
authors.lastname: Uysal
authors.affiliation: Medical School, Department of Biochemistry, Eskisehir Osmangazi University, 26480, Eskisehir, Turkey.
authors.forename: Aysegul
authors.initials: A
authors.lastname: Oglakci
authors.affiliation: Medical School, Department of Anatomy, Eskisehir Osmangazi University, 26480, Eskisehir, Turkey.
authors.forename: Ferruh
authors.initials: F
authors.lastname: Yucel
authors.affiliation: Medical School, Department of Biochemistry, Eskisehir Osmangazi University, 26480, Eskisehir, Turkey.
authors.forename: Kazim
authors.initials: K
authors.lastname: Kartkaya
authors.affiliation: Medical School, Department of Biochemistry, Eskisehir Osmangazi University, 26480, Eskisehir, Turkey.
authors.forename: Gungor
authors.initials: G
authors.lastname: Kanbak
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001622:Betaine / Q000627:therapeutic use*; D000067401:Blood Alcohol Content; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D056668:Cathepsin L / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000633:toxicity; D002540:Cerebral Cortex / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000067401:Blood Alcohol Content; D002492:Central Nervous System Depressants; D018696:Neuroprotective Agents; D000431:Ethanol; D001622:Betaine; D045304:Cytochromes c; D005492:Folic Acid; D002154:Calpain; D053148:Caspase 3; D002401:Cathepsin B; D056668:Cathepsin L
keywords: Betaine; Calpain; Caspase-3; Cytochrome c; Folic acid; Neuroapoptosis