Leanza G, Nilsson O G, Björklund A
Department of Medical Cell Research, University of Lund, Sweden.
Brain Res. 1993 Jun 25;615(1):147-59. doi: 10.1016/0006-8993(93)91126-d.
Lesions of the fimbria-fornix pathways are known to induce a partial cholinergic and noradrenergic denervation of the hippocampal formation, which is followed by a slow and protracted collateral sprouting by the spared afferents. Using the intracerebral microdialysis technique, compensatory changes in extracellular levels of acetylcholine (ACh) and noradrenaline (NA) have been monitored over time in the partially denervated hippocampus of awake unrestrained rats subjected to an unilateral fimbria-fornix (FF) transection. One week after the lesion, baseline ACh output was reduced by 90% and 80% in the dorsal and ventral hippocampus, respectively, and it remained depressed still by 6 months after lesion. KCl-evoked and atropine-stimulated ACh efflux were equally reduced by 1 week after lesion, remained depressed at 3 months, but showed a significant recovery by 6 months post-lesion. Tissue choline acetyltransferase (ChAT) activity levels, initially reduced by 92% and 86%, in the dorsal and ventral hippocampus, respectively, recovered significantly by 3 months and remained unchanged at 6 months. Baseline NA output was significantly reduced (-80%) in the dorsal hippocampus by 1 week after the lesion and showed a partial recovery over time (to 50% of normal), whereas the ventral part was not significantly affected by the FF lesion. The significant FF lesion-induced reduction in KCl- or desipramine (DMI)-stimulated NA release observed in the dorsal hippocampus at 1 week after the lesion remained unchanged during the subsequent months. By contrast, in the ventral hippocampus, the initial 65-70% reduction in KCl- and DMI-stimulated NA release significantly recovered to normal levels within 3 months post-lesion. The NA tissue levels were significantly reduced by 4 weeks after lesion, in the dorsal hippocampus and did not show any significant recovery over time. In the ventral hippocampus, these levels were significantly reduced only at 4 weeks. Transmitter turnover, expressed as the ratio between dialysate levels and tissue ChAT or NA content, showed a 3-fold increase in the dorsal hippocampus at 4 weeks after lesion, but not at later time points. This indicates that the spared noradrenergic and cholinergic afferents respond to the partial denervation by a transient increase in transmitter turnover, evident as early as 4 weeks post-lesion in the region of maximal denervation. This was followed by a long-term increase in evoked transmitter release which may result from a slowly progressing compensatory sprouting of the spared afferents.
已知穹窿-海马伞通路损伤会导致海马结构部分胆碱能和去甲肾上腺素能失神经支配，随后存活的传入纤维会出现缓慢而持久的侧支发芽。运用脑内微透析技术，对单侧穹窿-海马伞（FF）横断的清醒自由活动大鼠部分失神经支配的海马中，乙酰胆碱（ACh）和去甲肾上腺素（NA）细胞外水平随时间的代偿性变化进行了监测。损伤后1周，背侧和腹侧海马的基线ACh输出分别降低了90%和80%，损伤后6个月仍处于抑制状态。损伤后1周，KCl诱发和阿托品刺激的ACh流出同样降低，3个月时仍处于抑制状态，但损伤后6个月有显著恢复。组织胆碱乙酰转移酶（ChAT）活性水平，最初在背侧和腹侧海马分别降低了92%和86%，3个月时显著恢复，6个月时保持不变。损伤后1周，背侧海马的基线NA输出显著降低（-80%），并随时间部分恢复（至正常的50%），而腹侧部分未受FF损伤的显著影响。损伤后1周在背侧海马观察到的FF损伤导致的KCl或地昔帕明（DMI）刺激的NA释放显著减少，在随后几个月保持不变。相比之下，在腹侧海马，损伤后3个月内，KCl和DMI刺激的NA释放最初降低65 - 70%，显著恢复至正常水平。损伤后4周，背侧海马的NA组织水平显著降低，且随时间未显示任何显著恢复。在腹侧海马，这些水平仅在4周时显著降低。以透析液水平与组织ChAT或NA含量的比值表示的递质周转率，损伤后4周在背侧海马增加了3倍，但在后期时间点未增加。这表明存活的去甲肾上腺素能和胆碱能传入纤维对部分失神经支配的反应是递质周转率短暂增加，早在损伤后4周在失神经支配最严重的区域就很明显。随后是诱发递质释放的长期增加，这可能是由于存活传入纤维缓慢进展的代偿性发芽所致。
