PMID- 10526319 OWN - NLM STAT- MEDLINE DCOM- 19991210 LR - 20191103 IS - 0022-3034 (Print) IS - 0022-3034 (Linking) VI - 41 IP - 3 DP - 1999 Nov 15 TI - Alcohol exposure during the first two trimesters equivalent alters granule cell number and neurotrophin expression in the developing rat olfactory bulb. PG - 414-23 AB - Although alcohol has been shown to affect brain development adversely, the underlying mechanism of alcohol's actions are poorly understood. The present study addressed the hypothesis that alcohol affects growth factor availability during critical periods of neural growth by measuring the mRNA expression of brain-derived neurotrophic factor (BDNF), a potent developmental growth factor. Multiple offspring of timed-pregnant rat dams given alcohol (6.0 g/kg per day) or control treatments during gestation were sacrificed at either embryonic (E) day 21 or E33 (usually postnatal day 10) when their olfactory bulbs were processed for molecular analyses or neuron counting. BDNF mRNA levels were measured by reverse-transcription-polymerase chain reaction, and DNA methylation of the BDNF gene was quantified by Southern blot analyses following digestion with methylation-sensitive enzymes. Estimates of total granule cell number were obtained by counting those cells using unbiased stereological techniques. There was a significant decrease in BDNF mRNA levels in the alcohol-exposed offspring of both ages compared with controls. In addition, the number of olfactory bulb granule cells significantly decreased in the E33 but not the E21 rat pups exposed to alcohol compared with their appropriate aged controls. Finally, BDNF DNA of alcohol-exposed animals was less susceptible to digestion with the methylation-sensitive enzyme HpaII compared with controls, suggesting that the DNA of the alcohol exposed pups was hypermethylated. Our results indicate that exposure to alcohol during early brain development in the rat, a period equivalent to the first two trimesters in humans, can have a detrimental effect on normal development of the olfactory bulb by reducing the number of BDNF-synthesizing neurons. Although the exact mechanism for the alcohol-induced neuronal loss is unknown, the inappropriate transcription of the BDNF gene is one mechanism that may account for the complexity of effects observed in offspring exposed to heavy alcohol exposure in utero. CI - Copyright 1999 John Wiley & Sons, Inc. FAU - Maier, S E AU - Maier SE AD - Alcohol and Brain Research Laboratory and Department of Human Anatomy and Neurobiology, Texas A&M University System Health Science Center, College Station, Texas 77843-1114, USA. FAU - Cramer, J A AU - Cramer JA FAU - West, J R AU - West JR FAU - Sohrabji, F AU - Sohrabji F LA - eng GR - AA10090/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurobiol JT - Journal of neurobiology JID - 0213640 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Central Nervous System Depressants) RN - 0 (RNA, Messenger) RN - 3K9958V90M (Ethanol) SB - IM MH - Animals MH - Body Weight/drug effects MH - Brain-Derived Neurotrophic Factor/*genetics MH - Central Nervous System Depressants/adverse effects MH - Ethanol/*adverse effects MH - Female MH - Gene Expression/drug effects MH - Neurons/chemistry/cytology/*drug effects MH - Olfactory Bulb/cytology/*drug effects/*embryology MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - RNA, Messenger/analysis MH - Rats MH - Rats, Sprague-Dawley EDAT- 1999/10/20 00:00 MHDA- 1999/10/20 00:01 CRDT- 1999/10/20 00:00 PHST- 1999/10/20 00:00 [pubmed] PHST- 1999/10/20 00:01 [medline] PHST- 1999/10/20 00:00 [entrez] AID - 10.1002/(SICI)1097-4695(19991115)41:3<414::AID-NEU9>3.0.CO;2-F [pii] AID - 10.1002/(sici)1097-4695(19991115)41:3<414::aid-neu9>3.0.co;2-f [doi] PST - ppublish SO - J Neurobiol. 1999 Nov 15;41(3):414-23. doi: 10.1002/(sici)1097-4695(19991115)41:3<414::aid-neu9>3.0.co;2-f.