In vitro neurogenesis from neural progenitor cells isolated from the hippocampus region of the brain of adult rats exposed to ethanol during early development through their alcohol-drinking mothers.
OBJECTIVE
This study was aimed to determine whether ethanol exposure during early development altered neurogenesis in the brain of adult rats.


METHODS
Pregnant rats were given either ethanol-mixed or mannose-mixed (for control) rodent liquid diet ad libitum. Ethanol drinking continued during pregnancy and nursing. After weaning, the pups (AC(o): pups from control mothers, AE(o): pups from ethanol exposed mothers) received normal diet and water ad libitum for 11 weeks. Then the rats were anesthetized, their brains were collected and the hippocampal samples were processed for isolation of neural progenitor cells (NPCs). AC(o) NPCs and AE(o) NPCs were sequentially grown in media containing different growth factors that induced proliferation and differentiation.


CONCLUSIONS
Neuronal maturation was significantly delayed in ethanol-exposed rats. AC(o) NPCs, up to day 7 of culture, exhibited high beta-catenin-probe binding, an increase in Ca(2+) when exposed to gamma-amino butyric acid (GABA) and lack of response to glutamate (Glu) exposure. beta-Catenin-probe binding and the stimulatory effects of GABA declined thereafter. AC(o) NPCs, at culture day 29, exhibited high beta-catenin-probe binding, lack of response to GABA and elevated Glu-induced increase in Ca(2+i). Cultures of AE(o) NPCs showed an amplified stimulatory effects of GABA, attenuated stimulatory effects of Glu and attenuated the delayed (culture day 29) increase in the expression of Wnt proteins and beta-catenin-probe binding. This suggests a significant alteration in neurogenesis and synapse formation in adult rats exposed to ethanol at early development through their alcohol-drinking mothers.
Singh
Ashok K
AK
Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Twin Cities campus, St Paul, MN 55108, USA. singh001@umn.edu
Gupta
Shveta
S
Jiang
Yin
Y
Younus
Mohammed
M
Ramzan
Mohammed
M
D000079:Acetaldehyde / Q000097:blood; D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics / Q000473:pathology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000187:drug effects*; D013569:Synapses / Q000473:pathology; D016704:Synapsins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D000963:Antimetabolites; D002492:Central Nervous System Depressants; D016704:Synapsins; D000431:Ethanol; D012313:RNA; D003346:Corticotropin-Releasing Hormone; D001973:Bromodeoxyuridine; D000079:Acetaldehyde