Short-term ethanol exposure causes imbalanced neurotrophic factor allocation in the basal forebrain cholinergic system: a novel insight into understanding the initial processes of alcohol addiction.
Alcohol ingestion affects both motor and cognitive functions. One brain system that is influenced by ethanol is the basal forebrain (BF) cholinergic projection system, which projects to diverse neocortical and limbic areas. The BF is associated with memory and cognitive function. Our primary interest is the examination of how regions that receive BF cholinergic projections are influenced by short-term ethanol exposure through alterations in the mRNA levels of neurotrophic factors [nerve growth factor/TrkA, brain-derived neurotrophic factor/TrkB, and glial-derived neurotrophic factor (GDNF)/GDNF family receptor α1]. Male BALB/C mice were fed a liquid diet containing 5 % (v/v) ethanol. Pair-fed control mice were maintained on an identical liquid diet, except that the ethanol was isocalorically substituted with sucrose. Mice exhibiting signs of ethanol intoxication (stages 1-2) were used for real-time reverse transcription-polymerase chain reaction analyses. Among the BF cholinergic projection regions, decreased levels of GDNF mRNA and increased levels of TrkB mRNA were observed in the basal nucleus, and increased levels of TrkB mRNA were observed in the cerebral cortex. There were no significant alterations in the levels of expression of relevant neurotrophic factors in the septal nucleus and hippocampus. Given that neurotrophic factors function in retrograde/anterograde or autocrine/paracrine mechanisms and that BF cholinergic projection regions are neuroanatomically connected, these findings suggested that an imbalanced allocation of neurotrophic factor ligands and receptors is an initial phenomenon in alcohol addiction. The exact mechanisms underlying this phenomenon in the BF cholinergic system are unknown. However, our results provide a novel notion for the understanding of the initial processes in alcohol addiction.
Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University, Takamatsu, Japan, mikit@med.kagawa-u.ac.jp.
Takanori
T
Miki
Takashi
T
Kusaka
Toshifumi
T
Yokoyama
Ken-ichi
K
Ohta
Shingo
S
Suzuki
Katsuhiko
K
Warita
Mostofa
M
Jamal
Zhi-Yu
ZY
Wang
Masaaki
M
Ueki
Jun-Qian
JQ
Liu
Tomiko
T
Yakura
Motoki
M
Tamai
Kazunori
K
Sumitani
Naohisa
N
Hosomi
Yoshiki
Y
Takeuchi
D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000378:metabolism*; D002849:Chromatography, Gas; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism
D002492:Central Nervous System Depressants; D018678:Cholinergic Agents; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D000431:Ethanol