Aging is the major risk factor of the most common (∼95% of cases) sporadic Alzheimer’s disease (AD). Accumulating data indicate middle age as a critical period for the relevant pathological processes, however, the question of when AD starts to develop remains open. It has been reported only recently that in the early postnatal period—when brain development is completing—preconditions for a decrease in cognitive abilities and for accelerated aging can form. Here, we hypothesized that specific features of early postnatal brain development may be considered some of the prerequisites of AD development at an advanced age. To test this hypothesis, we used OXYS rats, which are a suitable model of sporadic AD. The duration of gestation, litter size, and weight at birth were lower in OXYS rats compared to control Wistar rats. The shortened duration of gestation may result in developmental retardation. Indeed, we noted decreased locomotor activity and increased anxiety in OXYS rats already at a young age: possible signs of altered brain development. We demonstrated retardation of the peak of postnatal neurogenesis in the hippocampal dentate gyrus of OXYS rats. Delayed neuronal maturation led to alterations of mossy-fiber formation: a shortened suprapyramidal bundle and longer infrapyramidal bundle, less pronounced fasciculation of granule cells’ axons, and smaller size and irregular shape of nuclei in the CA3 pyramidal layer. These changes were accompanied by altered astrocytic migration. The observed features of early development may be considered some of the risk factors of the AD-like pathology that manifests itself in OXYS rats late in life.

中文翻译：

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散发性阿尔茨海默病大鼠模型的出生后海马发育特征

衰老是最常见（约 95% 的病例）散发性阿尔茨海默病 (AD) 的主要危险因素。越来越多的数据表明，中年是相关病理过程的关键时期，然而，AD 何时开始发展的问题仍然悬而未决。最近才有报道称，在出生后早期——大脑发育完成时——认知能力下降和衰老加速的先决条件可以形成。在这里，我们假设出生后早期大脑发育的特定特征可能被认为是高龄 AD 发育的一些先决条件。为了验证这一假设，我们使用了 OXYS 大鼠，它们是散发性 AD 的合适模型。与对照 Wistar 大鼠相比，OXYS 大鼠的妊娠持续时间、窝产仔数和出生体重较低。妊娠期缩短可能导致发育迟缓。事实上，我们注意到 OXYS 大鼠在年轻时的运动活动减少，焦虑增加：大脑发育改变的可能迹象。我们证明了 OXYS 大鼠海马齿状回中出生后神经发生峰值的延迟。延迟的神经元成熟导致苔藓纤维形成的改变：缩短的锥体上束和更长的锥体下束，颗粒细胞轴突的不太明显的束状，以及 CA3 锥体层中较小尺寸和不规则形状的细胞核。这些变化伴随着星形胶质细胞迁移的改变。观察到的早期发育特征可能被认为是 AD 样病理的一些危险因素，这种病理在 OXYS 大鼠的晚年表现出来。