The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, Nanjing 210096, China.
Institute for Brain and Intelligence, Southeast University, Nanjing 210096, China.
J Neurosci. 2024 Mar 20;44(12):e1689232024. doi: 10.1523/JNEUROSCI.1689-23.2024.
As the most common form of dementia in the world, Alzheimer's disease (AD) is a progressive neurological disorder marked by cognitive and behavioral impairment. According to previous researches, abundant social connections shield against dementia. However, it is still unclear how exactly social interactions benefit cognitive abilities in people with AD and how this process is used to increase their general cognitive performance. In this study, we found that single novel social (SNS) stimulation promoted c-Fos expression and increased the protein levels of mature ADAM10/17 and sAPPα in the ventral hippocampus (vHPC) of wild-type (WT) mice, which are hippocampal dorsal CA2 (dCA2) neuron activity and vHPC NMDAR dependent. Additionally, we discovered that SNS caused similar changes in an AD model, FAD mice, and these alterations could be reversed by α-secretase inhibitor. Furthermore, we also found that multiple novel social (MNS) stimulation improved synaptic plasticity and memory impairments in both male and female FAD mice, accompanied by α-secretase activation and Aβ reduction. These findings provide insight into the process underpinning how social interaction helps AD patients who are experiencing cognitive decline, and we also imply that novel social interaction and activation of the α-secretase may be preventative and therapeutic in the early stages of AD.
作为世界上最常见的痴呆症形式，阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是认知和行为障碍。根据之前的研究，丰富的社会联系可以预防痴呆症。然而，目前尚不清楚社交互动究竟如何有益于 AD 患者的认知能力，以及如何利用这一过程来提高他们的整体认知表现。在这项研究中，我们发现单一新颖的社交（SNS）刺激可促进野生型（WT）小鼠腹侧海马（vHPC）中的 c-Fos 表达，并增加成熟的 ADAM10/17 和 sAPPα 的蛋白水平，这依赖于海马背侧 CA2（dCA2）神经元的活性和 vHPC 的 NMDAR。此外，我们发现 SNS 在 AD 模型 FAD 小鼠中也引起了类似的变化，而 α-分泌酶抑制剂可逆转这些变化。此外，我们还发现，多次新颖的社交（MNS）刺激可改善雄性和雌性 FAD 小鼠的突触可塑性和记忆障碍，同时伴随着 α-分泌酶的激活和 Aβ的减少。这些发现为社交互动如何帮助认知能力下降的 AD 患者提供了深入的了解，同时也暗示了新颖的社交互动和 α-分泌酶的激活在 AD 的早期阶段可能具有预防和治疗作用。
