Harkany T, O'Mahony S, Kelly J P, Soós K, Törõ I, Penke B, Luiten P G, Nyakas C, Gulya K, Leonard B E
Central Research Division, Haynal Imre University of Health Sciences, Budapest, Hungary.
Behav Brain Res. 1998 Feb;90(2):133-45. doi: 10.1016/s0166-4328(97)00091-0.
Long-term behavioral effects, changes in learning and memory functions and aberrations of cholinergic fibers projecting to the parietal cortex were investigated after bilateral injections of beta-amyloid(Phe(SO3H)24)25-35 peptide in rat nucleus basalis magnocellularis (nbm). The beta-amyloid peptide used in these experiments contained the original beta-amyloid 25-35 sequence which was coupled to a phenylalanine-sulphonate group at position 24. This additional residue serves as a protective cap on the molecule without influencing its neurotoxic properties and results in water-solubility, stability and low rates of peptide metabolism. In this paper, home cage, locomotor and open-field activities, passive shock-avoidance and 'Morris' water maze learning abilities were assessed throughout a 35-day survival period. Subsequently, acetylcholinesterase (AChE) histochemistry was used to visualize alterations of parietal cortical cholinergic innervation. In response to the neurotoxic action of beta-amyloid(Phe(SO3H)24)25-35, a progressive hyperactivity developed in the rats in their home cages which were maintained throughout the 5-week post-injection period. This was accompanied by a significant hypoactivity in the novel environment of a locomotor arena. Beta-amyloid(Phe(SO3H)24)25-35-treated animals showed greatly impaired cortical memory functions in the step-through passive shock-avoidance paradigm, while spatial learning processes remained unaffected. Moreover, beta-amyloid(Phe(SO3H)24)25-35 injections in the nucleus basalis suppressed explorative behavior in rats and inhibited conditioned stress responses 28 days after surgery. Reductions of cortical cholinergic (AChE-positive) projections provided anatomical substrate for the behavioral changes. This indicated extensive, long-lasting neurodegenerative processes as a result of beta-amyloid(Phe(SO3H)24)25-35 infusion.
在大鼠基底核大细胞部（nbm）双侧注射β-淀粉样蛋白（Phe(SO3H)24）25 - 35肽后，研究了其长期行为效应、学习和记忆功能的变化以及投射到顶叶皮质的胆碱能纤维的畸变情况。这些实验中使用的β-淀粉样肽包含原始的β-淀粉样蛋白25 - 35序列，该序列在第24位与苯丙氨酸磺酸盐基团相连。这个额外的残基作为分子上的保护帽，不影响其神经毒性特性，并导致水溶性、稳定性和低肽代谢率。在本文中，在整个35天的存活期内评估了家笼活动、自发活动和旷场活动、被动回避电击以及“莫里斯”水迷宫学习能力。随后，使用乙酰胆碱酯酶（AChE）组织化学来观察顶叶皮质胆碱能神经支配的改变。响应β-淀粉样蛋白（Phe(SO3H)24）25 - 35的神经毒性作用，大鼠在家笼中出现进行性多动，这种多动在注射后5周内一直持续。同时，在新的自发活动环境中出现明显的活动减少。经β-淀粉样蛋白（Phe(SO3H)24）25 - 35处理的动物在穿梭式被动回避电击范式中表现出皮质记忆功能严重受损，而空间学习过程未受影响。此外，在基底核注射β-淀粉样蛋白（Phe(SO3H)24）25 - 35可抑制大鼠的探索行为，并在手术后28天抑制条件性应激反应。皮质胆碱能（AChE阳性）投射的减少为行为变化提供了解剖学基础。这表明β-淀粉样蛋白（Phe(SO3H)24）25 - 35注入导致了广泛、持久的神经退行性过程。
