Fetal alcohol spectrum disorder-associated depression: evidence for reductions in the levels of brain-derived neurotrophic factor in a mouse model.
Prenatal ethanol exposure is associated with an increased incidence of depressive disorders in patient populations. However, the mechanisms that link prenatal ethanol exposure and depression are unknown. Several recent studies have implicated reduced brain-derived neurotrophic factor (BDNF) levels in the hippocampal formation and frontal cortex as important contributors to the etiology of depression. In the present studies, we sought to determine whether prenatal ethanol exposure is associated with behaviors that model depression, as well as with reduced BDNF levels in the hippocampal formation and/or medial frontal cortex, in a mouse model of fetal alcohol spectrum disorder (FASD). Compared to control adult mice, prenatal ethanol-exposed adult mice displayed increased learned helplessness behavior and increased immobility in the Porsolt forced swim test. Prenatal ethanol exposure was associated with decreased BDNF protein levels in the medial frontal cortex, but not the hippocampal formation, while total BDNF mRNA and BDNF transcripts containing exons III, IV or VI were reduced in both the medial frontal cortex and the hippocampal formation of prenatal ethanol-exposed mice. These results identify reduced BDNF levels in the medial frontal cortex and hippocampal formation as potential mediators of depressive disorders associated with FASD.
Department of Neurosciences, MSC 08 4740, 1 University of New Mexico, Albuquerque, NM 87131, USA. KCaldwell@salud.unm.edu
Kevin K
KK
Caldwell
S
S
Sheema
Rodrigo D
RD
Paz
Sabrina L
SL
Samudio-Ruiz
Mary H
MH
Laughlin
Nathan E
NE
Spence
Michael J
MJ
Roehlk
Sara N
SN
Alcon
Andrea M
AM
Allan
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000097:blood; D021984:Cyclophilin A / Q000378:metabolism; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003866:Depressive Disorder / Q000209:etiology / Q000378:metabolism* / Q000523:psychology*; D000431:Ethanol / Q000097:blood; D005091:Exons / Q000235:genetics; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism* / Q000523:psychology*; D006380:Helplessness, Learned; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013550:Swimming / Q000523:psychology
D019208:Brain-Derived Neurotrophic Factor; D002492:Central Nervous System Depressants; D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D000431:Ethanol; D007041:Hypoxanthine Phosphoribosyltransferase; D021984:Cyclophilin A