Biochemistry Research Institute of La Plata (INIBIOLP), National Scientific and Technical Research Council (CONICET), CC 455, zip code 1900 La Plata, Buenos Aires, Argentina; Cathedra of Histology and Embryology B-Cathedra of Pathology B, School of Medical Sciences, National University of La Plata (UNLP), CC 455, zip code 1900 La Plata, Buenos Aires, Argentina.
Biochemistry Research Institute of La Plata (INIBIOLP), National Scientific and Technical Research Council (CONICET), CC 455, zip code 1900 La Plata, Buenos Aires, Argentina; Cathedra of Histology and Embryology B-Cathedra of Pathology B, School of Medical Sciences, National University of La Plata (UNLP), CC 455, zip code 1900 La Plata, Buenos Aires, Argentina.
Behav Brain Res. 2022 Oct 28;435:114026. doi: 10.1016/j.bbr.2022.114026. Epub 2022 Aug 5.
Ageing is associated with impaired performance in recognition memory, a process that consists of the discrimination of familiar and novel stimuli. Previous studies have shown the impact of ageing on object recognition memories. However, the early stages of memory impairment remain unknown. To fill this gap, we aimed at evaluating the ability of young (Y), middle-aged (MA), and senile (S) female Sprague-Dawley rats to retain 24 h long-term recognition memory. The MA cohort was included to characterise early memory deficits under two behavioural paradigms based on spontaneous location recognition (SLR) and spontaneous object recognition (SOR) tasks. In the SLR task, there was a markedly diminished novel discrimination capacity in the MA and S rats compared with the Y ones. In the SOR task, S rats evidenced a deterioration in novelty discrimination, while MA rats partially preserved the capacity to distinguish the new stimulus as compared with Y rats. Regarding early changes from MA to S rats, immunohistochemistry showed a marked decrease in the number and diameter of adult-born immature neurons in the Dentate Gyrus (DG) with a positive correlation with behavioural performance in the SLR task. Furthermore, we found a slight reduction in CA3 mature neurons and a decrease in the number of total microglia in the perirhinal cortex (Prh) in MA and S rats as compared with Y rats. As regards changes that were only observed in S rats, we found an increase in the number of total and reactive microglia in CA3 and a reduction in the number of total microglia in the DG. We conclude that spatial discrimination capacity could be affected earlier than feature discrimination capacity. We suggest that early depletion of neurogenesis in MA rats is involved in object location recognition deficits, whereas the disruption of microglial homeostasis in the Prh could be associated with object feature discrimination capacity.
衰老是与识别记忆的表现受损相关的，这一过程包括对熟悉和新颖刺激的辨别。先前的研究表明了衰老对物体识别记忆的影响。然而，记忆损伤的早期阶段仍然未知。为了填补这一空白，我们旨在评估年轻（Y）、中年（MA）和老年（S）雌性 Sprague-Dawley 大鼠保留 24 小时长时识别记忆的能力。包含 MA 队列是为了在基于自发位置识别（SLR）和自发物体识别（SOR）任务的两个行为范式下，描述早期记忆缺陷。在 SLR 任务中，MA 和 S 大鼠与 Y 大鼠相比，新颖辨别能力明显降低。在 SOR 任务中，S 大鼠表现出新颖性辨别能力恶化，而 MA 大鼠与 Y 大鼠相比，部分保留了区分新刺激的能力。关于 MA 到 S 大鼠的早期变化，免疫组织化学显示齿状回（DG）中成年新生不成熟神经元的数量和直径明显减少，与 SLR 任务中的行为表现呈正相关。此外，我们发现 MA 和 S 大鼠的 CA3 成熟神经元数量略有减少，而边缘前皮质（Prh）中总小胶质细胞数量减少。至于仅在 S 大鼠中观察到的变化，我们发现 CA3 中总小胶质细胞和反应性小胶质细胞的数量增加，DG 中总小胶质细胞的数量减少。我们得出结论，空间辨别能力可能比特征辨别能力更早受到影响。我们认为 MA 大鼠中的神经发生早期耗竭参与了物体位置识别缺陷，而 Prh 中小胶质细胞的内稳态破坏可能与物体特征辨别能力有关。
