Developmental alcohol exposure disrupts circadian regulation of BDNF in the rat suprachiasmatic nucleus.
In rats, damage to neuronal populations in some brain regions occurs in response to neonatal alcohol exposure coinciding with the period of rapid brain growth. These alcohol-induced defects in brain development may persist into adulthood and thus have long-term implications for the functional characteristics of damaged neuronal populations. The present study examined the effects of neonatal alcohol exposure on endogenous rhythmicity of the circadian clock located in the rat suprachiasmatic nucleus (SCN). Specifically, experiments were conducted to determine whether neonatal alcohol exposure alters the circadian rhythm of brain-derived neurotrophic factor (BDNF) content in the rat SCN because this neurotrophin is an important rhythmic output from the SCN clock. Male rat pups were exposed to alcohol (4.5 g/kg/day) or isocaloric milk formula on postnatal days 4-9 using artificial rearing methods. At 5-6 months of age, SCN and hippocampal tissue was harvested and subsequently examined for content of BDNF protein. Time-dependent fluctuations in BDNF protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). In alcohol-treated rats, SCN levels of BDNF were significantly decreased and were characterized by a loss of circadian rhythmicity relative to those observed in control animals. In comparison, hippocampal levels of BDNF displayed no evidence of circadian regulation in all three treatment groups, but were slightly lower in alcohol-treated animals than in control groups. Importantly, these observations suggest that alcohol exposure during the period of rapid brain development may cause permanent changes in the SCN circadian clock.
Allen
Gregg C
GC
Department of Human Anatomy and Medical Neurobiology, The Texas A&M University System Health Science Center, 228 Reynolds Medical Building, College Station, TX 77843-1114, USA.
West
James R
JR
Chen
Wei-Jung A
WJ
Earnest
David J
DJ
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D002492:Central Nervous System Depressants; D000431:Ethanol