Involvement of the Hippocampus in Binge Ethanol-Induced Spleen Atrophy in Adolescent Rats.
Ethanol (EtOH) affects the immune system. Binge drinking of hard liquor initiates a stress response. This form of drinking is popular during adolescence, which involves maturation of the immune system. The spleen is a key immune organ, and spleen atrophy is associated with immunosuppression. While the hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the initial stress response, the hippocampus may be involved in stress beyond the HPA axis.



Blood ethanol concentration (BEC), blood endotoxin levels, and plasma corticosterone levels were measured following binge EtOH treatment. Absolute and relative spleen sizes were analyzed, and stress-related gene expression was compared in the hypothalamus and hippocampus. Polymerase chain reaction array was performed to analyze the expression profile of EtOH metabolism and immune regulation-related genes in the spleen. Relationships among variables were analyzed using the Pearson correlation.



At 24 hours following a 3-day EtOH treatment, no significant difference in BEC was detected between EtOH-treated and control rats. Average plasma endotoxin levels in EtOH-treated animals were significantly higher than in controls, and spleen size was significantly lower. Spleen size did not correlate with plasma endotoxin levels; however, it did significantly negatively correlate with plasma corticosterone levels. Spleen size significantly negatively correlated with hippocampal CRH expression and significantly positively correlated with hippocampal MR expression. No correlation was observed in the hypothalamus. Significantly higher hippocampal CRH and significantly lower MR expression was seen in low spleen/body weight (sp-wt) ratio rats. No gene was found to decrease expression ≥1.5-fold (p < 0.05) in the spleen of high sp-wt group, whereas expression of several genes, including Gabra1, Gabra5, Ifnb1, Irf9, Il12b, and Cx3cr1, decreased significantly in the low sp-wt group.



Our findings suggest that binge EtOH exposure causes lower spleen size in adolescents and that the hippocampus and stress may be associated with alterations in spleen structure and gene expression.
Department of Histology and Embryology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, New Jersey.
Xiangqian
X
Liu
Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, New Jersey.
Kaitlyn P
KP
Connaghan
Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, New Jersey.
Yufeng
Y
Wei
Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, New Jersey.
Zhongli
Z
Yang
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia.
Ming D
MD
Li
Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, New Jersey.|Department of Biological Sciences , Seton Hall University, South Orange, New Jersey.
Sulie L
SL
Chang
D000818:Animals; D001284:Atrophy / Q000473:pathology*; D063425:Binge Drinking / Q000097:blood / Q000473:pathology*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis; D004731:Endotoxins / Q000097:blood; D000431:Ethanol / Q000009:adverse effects* / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051381:Rats; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis; D013154:Spleen / Q000473:pathology*
D004731:Endotoxins; D018161:Receptors, Mineralocorticoid; D000431:Ethanol; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
Adolescents; Binge Drinking; Hippocampus; Spleen; Stress