Bielarczyk H, Tomsig J L, Suszkiw J B
Department of Physiology and Biophysics, University of Cincinnati College of Medicine, OH 45267-0576.
Brain Res. 1994 Apr 18;643(1-2):211-7. doi: 10.1016/0006-8993(94)90027-2.
We investigated the effects of low-level lead exposure on the postnatal development of cholinergic muscarinic receptors (mAChR) and a cholinergic marker enzyme cholineacetyltransferase (ChAT) activity in the rat septum and hippocampus. Rat pups were maternally lead-exposed by giving 0.2% lead acetate in drinking water to dams from one week before parturition (gestational day 16) through weaning at postnatal day 28. The lead-exposed litters had blood Pb in the range 20 micrograms/dl and tissue Pb < 0.2 micrograms/g in both the septum and hippocampus. Associated with this level of lead exposure there was a significant 30-40% reduction in the ChAT activity in the septa and hippocampi of PN7 through PN28 animals. In contrast, the levels of glutamic acid decarboxylase (GAD) activity, a GABAergic neuron marker enzyme, were not altered in either brain region. Associated with the selective reduction of ChAT activity there was a parallel 30-40% reduction of the [3H]quinuclidinyl benzilate, [3H]AF-DX 384, and [3H]pirenzepine binding in the septum, however muscarinic ligand binding in the hippocampus of lead exposed animals was not affected. These results indicate preferential vulnerability of septal cholinergic neurons to adverse effects of low-level Pb exposure and suggest that impaired expression of muscarinic receptors and disruption of muscarinic transmission in the septum may be an important factor in cognitive and learning deficits associated with developmental low-level lead exposure.
我们研究了低水平铅暴露对大鼠中隔和海马中胆碱能毒蕈碱受体（mAChR）的产后发育以及胆碱能标记酶胆碱乙酰转移酶（ChAT）活性的影响。从分娩前一周（妊娠第16天）至出生后第28天断奶，通过给母鼠饮用含0.2%醋酸铅的水，使幼鼠在母体中暴露于铅。铅暴露组幼鼠血液中的铅含量在20微克/分升范围内，中隔和海马组织中的铅含量均<0.2微克/克。与这种铅暴露水平相关的是，出生后第7天至第28天的动物中隔和海马中的ChAT活性显著降低了30 - 40%。相比之下，γ-氨基丁酸能神经元标记酶谷氨酸脱羧酶（GAD）的活性在两个脑区均未改变。与ChAT活性的选择性降低相关，中隔中[³H]喹核醇基苯甲酸酯、[³H]AF-DX 384和[³H]哌仑西平的结合也平行降低了30 - 40%，然而，铅暴露动物海马中的毒蕈碱配体结合未受影响。这些结果表明中隔胆碱能神经元对低水平铅暴露的不利影响具有优先易损性，并提示中隔中毒蕈碱受体表达受损和毒蕈碱传递中断可能是与发育性低水平铅暴露相关的认知和学习缺陷的一个重要因素。
