Neuroactive Steroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP) and Pro-inflammatory Cytokine MCP-1 Levels in Hippocampus CA1 are Correlated with Voluntary Ethanol Consumption in Cynomolgus Monkey.
Neuroactive Steroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP) and Pro-inflammatory Cytokine MCP-1 Levels in Hippocampus CA1 are Correlated with Voluntary Ethanol Consumption in Cynomolgus Monkey.
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DOI：
10.1111/acer.13545
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Morrow AL
中科院分区：
文献类型：
--
作者：
Beattie MC;Reguyal CS;Porcu P;Daunais JB;Grant KA;Morrow AL
神经活性类固醇如（3α,5α）3-羟基孕酮-20-酮（3α,5α- thp，异孕酮）是有效的神经调节剂，可增强gaba能神经传递，产生抑制神经行为和抗炎作用。慢性乙醇消耗降低人血浆中3α，5α-THP水平，但对中枢神经系统中3α，5α-THP水平有脑区和物种特异性影响。我们探讨了食蟹猴在连续12个月每天自我给药乙醇后，海马中3α、5α-THP水平与自愿乙醇消耗之间的关系，并进一步研究了乙醇暴露前与HPA轴功能的关系。我们同时研究了慢性自我给药后海马单核细胞趋化蛋白1 （MCP-1）的水平，MCP-1是一种促炎细胞因子，在对乙醇的神经免疫反应中起重要作用。在4个月的时间里，猴子接受预定的诱导水和乙醇消耗（0-1.5 g/kg），然后在12个月的时间里每天自由使用乙醇或水22小时。采用抗3α、5α-THP或抗mcp -1抗体进行免疫组化。长期自愿饮酒导致乙醇消耗量的个体差异，在12个月内为1.2 - 4.2 g/kg/天。长时间乙醇消耗使海马CA1细胞3α，5α-THP免疫反应性提高12±2% (p<0.05)，使MCP-1免疫反应性降低23±9% （p<0.05）。在这两种情况下，酒精的影响在重度饮酒者中最为明显，饮酒者在≥20%的天数中消耗≥3g /kg。3α，5α-THP免疫反应性与平均每日乙醇摄入量（Spearman r = 0.75, p<0.05）和地塞米松抑制HPA轴功能（Spearman r = 0.9, p<0.05）呈正相关。相反，MCP-1免疫反应性与平均每日乙醇摄入量（Spearman r = - 0.78, p<0.05）和地塞米松抑制HPA轴功能（Spearman r = - 0.76, p<0.05）呈负相关。3α、5α-THP和MCP-1免疫反应性呈负相关（Spearman r= - 0.68, P < 0.05）。这些数据表明，长期自愿乙醇消耗导致CA1海马区3α，5α-THP水平升高，而MCP-1水平降低，这两种变化可能与HPA轴功能和自愿乙醇消耗的大小有关。
Neuroactive steroids such as (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone) are potent neuromodulators that enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Chronic ethanol consumption reduces 3α,5α-THP levels in human plasma, but has brain-region and species-specific effects on CNS levels of 3α,5α-THP. We explored the relationship between 3α,5α-THP levels in the hippocampus and voluntary ethanol consumption in the cynomolgus monkey following daily self-administration of ethanol for 12 months and further examined the relationship to HPA axis function prior to ethanol exposure. We simultaneously explored hippocampus levels of monocyte chemoattractant protein 1 (MCP-1), a pro-inflammatory cytokine that plays an important role in the neuroimmune response to ethanol, following chronic self-administration. Monkeys were subjected to scheduled induction of water and ethanol consumption (0–1.5 g/kg) over four months, followed by free access to ethanol or water for 22 hours/day over twelve months. Immunohistochemistry was performed using an anti-3α,5α-THP or anti-MCP-1 antibody. Prolonged voluntary drinking resulted in individual differences in ethanol consumption that ranged from 1.2 – 4.2 g/kg/day over 12 months. Prolonged ethanol consumption increased cellular 3α,5α-THP immunoreactivity by 12±2% (p<0.05) and reduced MCP-1 immunoreactivity by 23±9% (p<0.05) in the hippocampus CA1. In both cases, the effect of ethanol was most pronounced in heavy drinkers that consumed ≥3 g/kg for ≥20% of days. 3α,5α-THP immunoreactivity was positively correlated with average daily ethanol intake (Spearman r = 0.75, p<0.05) as well as dexamethasone inhibition of HPA axis function (Spearman r = 0.9, p<0.05. In contrast, MCP-1 immunoreactivity was negatively correlated with average daily ethanol intake (Spearman r = −0.78, p<0.05) as well as dexamethasone suppression of HPA axis function (Spearman r = − 0.76, p<0.05). Finally, 3α,5α-THP and MCP-1 immunoreactivity were inversely correlated with each other (Spearman r=−0.68, P < 0.05). These data indicate that voluntary, long-term ethanol consumption results in higher levels of 3α,5α-THP, while decreasing levels of MCP-1 in the CA1 hippocampus, and that both changes may be linked to HPA axis function and the magnitude of voluntary ethanol consumption.
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影响因子：
2.9
作者：
Hueston, Cara M.;Deak, Terrence
通讯作者：
Deak, Terrence
影响因子：
3.4
作者：
Beattie MC;Maldonado-Devincci AM;Porcu P;O'Buckley TK;Daunais JB;Grant KA;Morrow AL
通讯作者：
Morrow AL
影响因子：
10.6
作者：
Crews, Fulton T.;Qin, Liya;Sheedy, Donna;Vetreno, Ryan P.;Zou, Jian
通讯作者：
Zou, Jian
DOI：
10.1111/j.1530-0277.2011.01685.x
发表时间：
2012-06-01
影响因子：
3.2
作者：
Helms, Christa M.;Messaoudi, Ilhem;Grant, Kathleen A.
通讯作者：
Grant, Kathleen A.
影响因子：
2.9
作者：
BITRAN, D;HILVERS, RJ;KELLOGG, CK
通讯作者：
KELLOGG, CK