Lasley S M, Green M C, Gilbert M E
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria, USA.
Neurotoxicology. 1999 Aug;20(4):619-29.
Previous work has demonstrated that continual exposure to 0.2% lead (Pb) beginning at birth diminishes depolarization-induced hippocampal glutamate (GLU) and GABA release in vivo. The present study sought to extend these findings by examining Pb-induced changes as a function of exposure period. Rats were continually exposed to 0.2% Pb in the drinking water beginning at conception (Gestational-Life, GL) or two weeks after weaning (Wean-Life, WL), while exposure in a third group was begun at conception but terminated at weaning (Gestational-Wean, GW). Hippocampal transmitter release was induced in adult animals by perfusion of 150 mM K+ in the presence of Ca+2 (total release) through a microdialysis probe in one test session, followed by perfusion through a contralateral probe in the absence of Ca+2 (Ca+2-independent release) in the second session. Decreases in total GLU and GABA release were observed in the GL and WL groups compared to controls over the first 20-min after initiation of high K+, decrements that could be attributed to exposure-induced reductions in Ca+2-dependent release. The pattern of Pb-induced changes in the GL group is similar to that observed previously in a group continuously exposed from birth, indicating that gestational exposure did not further enhance the impact of Pb beginning at birth when exposure in both groups extends into adulthood. Similar responses were also found in the WL group, indicating that exposure during early development is not a requirement to induce changes in GLU and GABA release. Pb-induced decreases in response were also seen in the GW group: a decrease in Ca+2-dependent GLU release was observed, while decrements in total and Ca+2-dependent GABA release were similar to those in the GL and WL groups. Thus, exposure limited to early development is also sufficient to produce deficits in evoked transmitter release. In addition, the exposure-induced decreases in GLU responses correspond to Pb-induced impairments in long-term potentiation (LTP) observed in similarly exposed groups (Gilbert et al., 1999), providing further evidence that Pb effects on GLU release are a critical factor in the alterations found in LTP.
先前的研究表明，从出生开始持续接触0.2%的铅（Pb）会减少体内去极化诱导的海马谷氨酸（GLU）和γ-氨基丁酸（GABA）释放。本研究试图通过检查铅诱导的变化作为暴露时间的函数来扩展这些发现。大鼠从受孕开始（孕期-终生，GL）或断奶后两周（断奶-终生，WL）持续饮用含0.2%铅的水，而第三组从受孕开始暴露，但在断奶时终止（孕期-断奶，GW）。在一个测试环节中，通过微透析探针在存在Ca+2的情况下灌注150 mM K+（总释放）来诱导成年动物海马神经递质释放，随后在第二个环节中通过对侧探针在不存在Ca+2的情况下灌注（Ca+2非依赖性释放）。与对照组相比，在高钾灌注后的前20分钟内，GL组和WL组的总GLU和GABA释放减少，这些减少可归因于暴露诱导的Ca+2依赖性释放减少。GL组中铅诱导的变化模式与先前从出生开始持续暴露的一组中观察到的模式相似，表明孕期暴露在两组暴露都持续到成年时，并没有进一步增强从出生开始的铅的影响。在WL组中也发现了类似的反应，表明早期发育期间的暴露不是诱导GLU和GABA释放变化的必要条件。在GW组中也观察到了铅诱导的反应降低：观察到Ca+2依赖性GLU释放减少，而总GABA和Ca+2依赖性GABA释放的减少与GL组和WL组相似。因此，仅限于早期发育的暴露也足以导致诱发的神经递质释放缺陷。此外，暴露诱导的GLU反应降低与在类似暴露组中观察到的铅诱导的长时程增强（LTP）损伤相对应（Gilbert等人，1999）这进一步证明了铅对GLU释放的影响是LTP改变的关键因素。
