Hong S J, Grover C A, Safe S H, Tiffany-Castiglioni E, Frye G D
Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station 77843, USA.
Toxicol Appl Pharmacol. 1998 Jan;148(1):7-13. doi: 10.1006/taap.1997.8317.
Halogenated aromatic hydrocarbons (HAHs), such as polychlorinated biphenyls (PCBs) and dibenzo-p-dioxins (PCDDs), alter cognitive function and learning. The cellular basis of HAH-induced alteration of brain function is not well-understood. The hippocampus is a likely site of toxic action because of its well-known roles in learning and memory, as well as its propensity to accumulate environmental neurotoxicants. A hippocampal function that can be measured readily is evoked excitatory postsynaptic potentials (EPSPs), which are an index of excitatory synaptic function. In this study, effects of HAHs on EPSPs were characterized in hippocampal slices from adolescent to adult male Sprague-Dawley rats. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,3,4-TCDD were used because these HAHs are prototypical potent and weak aryl hydrocarbon (Ah) receptor agonists, respectively. 2,2',5,5'-Tetrachlorobiphenyl (TCB) was used as a prototypical ortho-substituted PCB, which acts through Ah receptor-independent pathways. For each hippocampal slice, peak amplitudes of EPSPs during a 15-min recording period (1 recording/min) were averaged and used as baseline (100%). Subsequent EPSPs were expressed as percentage of baseline. TCDD and 1,2,3,4-TCDD did not alter EPSPs in slices from the middle third of the hippocampus. However, in ventral slices, TCDD significantly decreased EPSPs, whereas 1,2,3,4-TCDD was inactive. TCB decreased EPSPs in both middle and ventral slices at half-maximal stimulation. An unexpected reversal of inhibition was observed within 30 min of continuous application of TCDD or TCB. In ventral slices, L-type calcium channel blocker nifedipine blocked inhibition of EPSPs induced by TCDD but not EPSPs inhibited by TCB. These results suggest that, while TCB-induced inhibition of EPSPs occurs through an unknown mechanism, TCDD-induced inhibition of EPSPs was mediated by L-type calcium channel activity in a congener-specific manner.
卤代芳烃（HAHs），如多氯联苯（PCBs）和二苯并 - p - 二恶英（PCDDs），会改变认知功能和学习能力。HAH诱导的脑功能改变的细胞基础尚未完全明确。海马体可能是毒性作用的部位，因为它在学习和记忆中具有众所周知的作用，并且易于积累环境神经毒素。一种易于测量的海马体功能是诱发兴奋性突触后电位（EPSPs），它是兴奋性突触功能的指标。在本研究中，在青春期至成年雄性Sprague-Dawley大鼠的海马体切片中，对HAHs对EPSPs的影响进行了表征。使用2,3,7,8 - 四氯二苯并 - p - 二恶英（TCDD）和1,2,3,4 - 四氯二苯并 - p - 二恶英，因为这些HAHs分别是典型的强效和弱效芳烃（Ah）受体激动剂。2,2',5,5'-四氯联苯（TCB）用作典型的邻位取代多氯联苯，其通过不依赖Ah受体的途径起作用。对于每个海马体切片，在15分钟记录期（每分钟记录1次）内EPSPs的峰值幅度进行平均并用作基线（100%）。随后的EPSPs表示为基线的百分比。TCDD和1,2,3,4 - TCDD在海马体中三分之一的切片中未改变EPSPs。然而，在腹侧切片中，TCDD显著降低EPSPs，而1,2,3,4 - TCDD无活性。在半最大刺激下，TCB在中侧和腹侧切片中均降低了EPSPs。在持续应用TCDD或TCB的30分钟内观察到了意外的抑制逆转。在腹侧切片中，L型钙通道阻滞剂硝苯地平阻断了TCDD诱导的EPSPs抑制，但未阻断TCB抑制的EPSPs。这些结果表明，虽然TCB诱导的EPSPs抑制通过未知机制发生，但TCDD诱导的EPSPs抑制是以同系物特异性方式由L型钙通道活性介导的。
