Sex and regional differences in effects of chronic intermittent ethanol exposure on subsequent excitotoxic challenges in hippocampal slice cultures.
Sex and regional differences in effects of chronic intermittent ethanol exposure on subsequent excitotoxic challenges in hippocampal slice cultures.
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慢性间歇性乙醇暴露对海马切片培养物随后的兴奋性毒性挑战的影响的性别和区域差异。
DOI：
10.1016/j.neulet.2013.05.011
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发表时间：
2013
影响因子：
2.5
通讯作者：
Devaud,LeslieL
中科院分区：
文献类型：
--
作者：
Walls,ShawnA;Rosenwasser,AlanM;Devaud,LeslieL
器官型海马切片培养技术用于研究男性和女性之间重复乙醇戒断的影响在细胞水平上可能有何不同，包括对后续损伤的潜在调节。采用慢性间歇性乙醇 (CIE) 暴露范例，暴露 3 天，然后 24 小时停药，共 3 个周期。接下来将切片暴露于皮质酮 (CORT) 或戊四唑 (PTZ) 24 小时，然后成像以获得碘化丙啶 (PI) 信号强度。海马切片培养物的 CA1 区和齿状回对 CIE 和/或 CORT 或 PTZ 治疗存在性别选择性反应。单独使用 50 mM CIE 通常不会增加 PI 信号，但会增强对 CORT（特别是女性）和 PTZ（特别是男性）毒性作用的敏感性。相比之下，100 mM CIE 引起的毒性反应在女性中比男性更大，并且由于暴露于 PTZ 而加剧。这些数据表明，即使在未成熟状态下，海马的性别二态性也会影响对乙醇和其他有毒化学物质的敏感性。低剂量 CIE 可能会以海马性别和区域选择性的方式减轻额外挑战带来的伤害。这些发现为慢性乙醇暴露和戒断反应中重要的神经生物学性别差异提供了越来越多的证据。
The organotypic hippocampal slice culture technique was used to study how the effects of repeated ethanol withdrawal might differ between males and females at the cellular level, including potential modulation of subsequent insults. A chronic intermittent ethanol (CIE) exposure paradigm was employed, with 3 days of exposure followed by 24 h withdrawal for 3 cycles. Slices were next exposed to corticosterone (CORT) or pentylenetetrazol (PTZ) for 24 h then imaged for propidium iodide (PI) signal intensities. There were sex-selective responses in the CA1 region and dentate gyrus of the hippocampal slice cultures to treatment with CIE and/or CORT or PTZ. The 50 mM CIE alone generally did not increase the PI signal, but enhanced sensitivity to the toxic effects of CORT (particularly for females) and PTZ (particularly for males). In contrast, 100 mM CIE elicited a toxic response that was greater in females than males, and was exacerbated by exposure to PTZ. These data showed that hippocampal sexual dimorphism influences sensitivity to ethanol and other toxic chemicals even in an immature state. Low-dose CIE may attenuate harm from additional challenges in a hippocampal sex- and region-selective manner. These findings add to the growing evidence of important neurobiological sex differences in responses to chronic ethanol exposure and withdrawal.