Erb C, Klein J, Köppen A, Löffelholz K, Jeltsch H, Cassel J C
Pharmakologisches Institut der Universität Mainz, Germany.
Neurosci Lett. 1997 Aug 1;231(1):5-8. doi: 10.1016/s0304-3940(97)00504-1.
Female Long-Evans rats sustained electrolytic lesions of the fimbria and the dorsal fornix causing a partial lesion of the septohippocampal pathway. Two weeks later, the rats received intra-hippocampal grafts of fetal septal cell suspensions. Nine to twelve months later, the release of acetylcholine (ACh) in the hippocampus of sham-operated, lesion-only and grafted rats was measured by microdialysis. The extent of cholinergic (re)innervation was determined by acetylcholinesterase (AChE) staining and densitometry. In both lesion-only and grafted rats, the ratio of ACh release to AChE staining intensity was increased as compared to sham-operated rats, indicating a loss of endogenous inhibitory mechanisms. Scopolamine (0.5 mg/kg i.p.), a muscarinic antagonist, increased ACh release in all treatment groups. 8-OH-DPAT (0.5 mg/kg s.c.), an agonist at serotonergic 5HT1A-receptors, induced an increase of hippocampal ACh release in sham-operated rats. This effect was lost in lesion-only rats, but was fully restored by neuronal grafting. As 8-OH-DPAT influences hippocampal ACh release by a postsynaptic action, this finding indicates that the host brain exerts a serotonergic influence on the grafted cholinergic neurons.
雌性Long-Evans大鼠接受了穹窿和背侧穹窿的电解损伤，导致隔海马通路部分受损。两周后，这些大鼠接受了胎鼠隔细胞悬液的海马内移植。9至12个月后，通过微透析测量假手术组、仅损伤组和移植组大鼠海马中乙酰胆碱（ACh）的释放。通过乙酰胆碱酯酶（AChE）染色和光密度测定法确定胆碱能（再）神经支配的程度。与假手术组大鼠相比，仅损伤组和移植组大鼠的ACh释放与AChE染色强度之比均升高，表明内源性抑制机制丧失。毒蕈碱拮抗剂东莨菪碱（0.5mg/kg腹腔注射）可增加所有治疗组的ACh释放。5-羟色胺能5HT1A受体激动剂8-OH-DPAT（0.5mg/kg皮下注射）可诱导假手术组大鼠海马ACh释放增加。这种效应在仅损伤组大鼠中消失，但通过神经元移植完全恢复。由于8-OH-DPAT通过突触后作用影响海马ACh释放，这一发现表明宿主脑对移植的胆碱能神经元发挥5-羟色胺能影响。
