Gilad G M, Rabey J M, Tizabi Y, Gilad V H
Center for Neuroscience and Behavioral Research, Weizmann Institute of Science, Rehovot, Israel.
Brain Res. 1987 Dec 15;436(2):311-22. doi: 10.1016/0006-8993(87)91675-1.
Inbred Wistar-Kyoto rats which are behaviorally more reactive to stress have a shorter life span than Brown-Norway rats. This is paralleled by higher basal activity and more pronounced changes in the septohippocampal cholinergic system of Wistar-Kyotos after stress. Age- and strain-dependent differences were therefore characterized in the septohippocampal system of 3- and 24-month-old (aged) Wistar-Kyotos and Brown-Norways, and in 30-month-old Brown-Norways. High affinity [3H]choline uptake and newly synthesized [3H]acetylcholine release served as markers for cholinergic terminals in the hippocampus. [3H]Quinuclidinylbenzilate binding served as a marker of muscarinic receptors in the hippocampus. Choline acetyltransferase activity served as a marker for cholinergic neurons and their terminals in the septum and hippocampus respectively. Acetylcholinesterase histochemical staining served to localize cholinergic neurons and their terminals in the septum and hippocampus respectively. In the hippocampus of aged Wistar-Kyotos choline uptake and acetylcholine release were reduced by approximately 50% compared to their young counterparts, but remained unchanged in aged Brown-Norways. Hippocampal choline acetyltransferase activity, acetylcholinesterase staining and muscarinic binding were unchanged in aged rats of both strains. Pyramidal cell loss (observed in Cresyl violet stained sections) was detected in hippocampus of 24-month-old Wistar-Kyotos and 30-month-old, but not younger Brown-Norways. Numbers of acetylcholinesterase-stained cells in the septum were reduced by 45 and 25% in 24-month-old Wistar-Kyotos and Brown-Norways respectively, and by 50% in 30-month-old Brown-Norways. Mean diameter of these cells was increased only in aged Wistar-Kyotos (approximately 46%) and in 30-month-old Brown-Norways (40%). The results indicate: (1) there is an ongoing age-dependent degeneration of septohippocampal cholinergic neurons which is associated with two principal compensatory changes in remaining cholinergic neurons: (a) hypertrophy of perikarya and (b) relative increase in activity of presynaptic markers in terminals with unchanged regional distribution, suggesting possible collateral sprouting; (2) age-dependent loss of septal cholinergic neurons precedes loss of hippocampal pyramidal neurons and (3) loss of pyramidal neurons in the hippocampus is associated with a compensatory increased muscarinic binding by remaining target hippocampal neurons. The results imply that higher basal and stress-induced activity of septohippocampal cholinergic neurons may be correlated with an accelerated and more pronounced age-dependent degeneration of this cholinergic system.(ABSTRACT TRUNCATED AT 400 WORDS)
对压力行为反应更强的近交系Wistar-Kyoto大鼠的寿命比Brown-Norway大鼠短。这与Wistar-Kyoto大鼠更高的基础活性以及应激后海马隔区胆碱能系统更明显的变化相平行。因此，对3个月和24个月大（老龄）的Wistar-Kyoto大鼠和Brown-Norway大鼠以及30个月大的Brown-Norway大鼠的海马隔区系统中的年龄和品系依赖性差异进行了表征。高亲和力[3H]胆碱摄取和新合成的[3H]乙酰胆碱释放作为海马中胆碱能终末的标志物。[3H]喹核酯苄酯结合作为海马中毒蕈碱受体的标志物。胆碱乙酰转移酶活性分别作为隔区和海马中胆碱能神经元及其终末的标志物。乙酰胆碱酯酶组织化学染色分别用于定位隔区和海马中的胆碱能神经元及其终末。在老龄Wistar-Kyoto大鼠的海马中，胆碱摄取和乙酰胆碱释放与其年轻对应物相比减少了约50%，但在老龄Brown-Norway大鼠中保持不变。两种品系老龄大鼠的海马胆碱乙酰转移酶活性、乙酰胆碱酯酶染色和毒蕈碱结合均未改变。在24个月大的Wistar-Kyoto大鼠和30个月大的Brown-Norway大鼠（而非更年轻的Brown-Norway大鼠）的海马中检测到锥体细胞丢失（在甲酚紫染色切片中观察到）。24个月大的Wistar-Kyoto大鼠和Brown-Norway大鼠隔区中乙酰胆碱酯酶染色细胞的数量分别减少了45%和25%，30个月大的Brown-Norway大鼠减少了50%。这些细胞的平均直径仅在老龄Wistar-Kyoto大鼠（约46%）和30个月大的Brown-Norway大鼠（40%）中增加。结果表明：（1）海马隔区胆碱能神经元存在随年龄增长的持续退化，这与剩余胆碱能神经元的两个主要代偿性变化相关：（a）胞体肥大和（b）终末中突触前标志物活性相对增加，区域分布不变，提示可能有侧支发芽；（2）隔区胆碱能神经元随年龄的丢失先于海马锥体细胞的丢失；（3）海马中锥体细胞的丢失与剩余海马靶神经元代偿性增加的毒蕈碱结合相关。结果表明，海马隔区胆碱能神经元更高的基础活性和应激诱导活性可能与该胆碱能系统加速且更明显的随年龄退化相关。（摘要截取自400字）
