Bielarczyk H, Tian X, Suszkiw J B
Department of Molecular and Cellular Physiology, University of Cincinnati, OH 45267-0576, USA.
Brain Res. 1996 Feb 5;708(1-2):108-15. doi: 10.1016/0006-8993(95)01315-6.
We investigated the effects of developmental lead exposure from embryonic day 16 (E16) through postnatal day 28 (PN28), on cholinergic and catecholaminergic markers in the septohippocampal pathway in rats through fourth month of age. Lead exposure resulted in a persistent 30-40% reduction of [3H]hemicholinium-3 ([3H]HC-3) binding in the hippocampus through PN120, and 20-30% reduction of septal and hippocampal choline acetyltransferase (ChAT) activity which persisted through PN84 but returned to control levels in both septum and hippocampus at PN112. The muscarinic ligand [3H]quinuclidinyl benzylate ([3H]QNB) binding was reduced in the septum at PN28 but did not differ significantly from controls at PN56-PN112. Neither short- nor long-term effects of Pb exposure on [3H]QNB binding were seen in the hippocampus. Similar to the effects of fimbria-fornix transection, Pb exposure resulted in a long-term 50-90% increase of tyrosine hydroxylase(TH) activity in the hippocampus, although neither treatment affected TH activity in the septum. The lead-induced increase in hippocampal TH was significantly attenuated by superior cervical ganglionectomy. It is concluded that the effects of perinatal lead exposure resemble in several respects those seen following surgical disruption of the septohippocampal pathway in adult animals. The denervation-like effects in the hippocampus may be an important factor in long-term learning and cognitive impairments following developmental exposure to low-levels of lead.
我们研究了从胚胎第16天（E16）至出生后第28天（PN28）发育期间铅暴露，对4月龄大鼠海马隔区通路中胆碱能和儿茶酚胺能标志物的影响。铅暴露导致海马中[3H]半胱氨酸转运体-3（[3H]HC-3）结合在PN120之前持续降低30%-40%，隔区和海马胆碱乙酰转移酶（ChAT）活性在PN84之前持续降低20%-30%，但在PN112时隔区和海马的ChAT活性均恢复到对照水平。M胆碱能配体[3H]喹核醇基苯甲酸酯（[3H]QNB）结合在PN28时在隔区降低，但在PN56-PN112时与对照无显著差异。在海马中未观察到铅暴露对[3H]QNB结合的短期或长期影响。与穹窿海马伞横断的影响相似，铅暴露导致海马中酪氨酸羟化酶（TH）活性长期增加50%-90%，尽管两种处理均未影响隔区的TH活性。颈上神经节切除术可显著减弱铅诱导的海马TH增加。结论是围产期铅暴露的影响在几个方面类似于成年动物海马隔区通路手术破坏后的影响。海马中的去神经样效应可能是发育期间低水平铅暴露后长期学习和认知障碍的一个重要因素。
