Černotová Daniela, Hrůzová Karolína, Touš Jan, Janča Radek, Stuchlík Aleš, Levčík David, Svoboda Jan
Laboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, Prague 142 00, Czech Republic; Third Faculty of Medicine, Charles University, Ruska 87, Prague 100 00, Czech Republic.
Laboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, Prague 142 00, Czech Republic; Faculty of Electrical Engineering, Czech Technical University in Prague, Technicka 2, Prague 160 00, Czech Republic.
Neurobiol Dis. 2025 May;208:106875. doi: 10.1016/j.nbd.2025.106875. Epub 2025 Mar 15.
Social withdrawal and deficits in social cognition are hallmarks of Alzheimer's disease (AD). While early deficits in social behavior and memory have been documented in mouse AD models, they remain understudied in rat models. Early-stage AD is accompanied by dysfunction of parvalbumin-positive (PV+) interneurons, implicating their potential connection to early symptoms. In this study, we employed a 5-trial social memory task to investigate early deficits in social cognition in 6-month-old TgF344-AD male and female rats. We counted the number of PV+ interneurons and recorded local field potentials during social interactions in the hippocampal CA2 - a region critical for social information processing. Our results show decreased social interest and novelty preference in TgF344-AD male and female rats. However, reduced PV+ interneuron numbers were observed only in female rats and specific to the CA2 area. The electrophysiological recordings revealed reduced theta-gamma phase-amplitude coupling in the CA2 during direct social interactions. We conclude that deficits in social cognition accompany early-stage AD in TgF344-AD rats and are potentially linked to PV+ interneuron and brain oscillatory dysfunction in the CA2 region of the hippocampus.
社交退缩和社会认知缺陷是阿尔茨海默病（AD）的标志。虽然在小鼠AD模型中已记录到早期社交行为和记忆缺陷，但在大鼠模型中仍未得到充分研究。早期AD伴有小白蛋白阳性（PV+）中间神经元功能障碍，这暗示了它们与早期症状的潜在联系。在本研究中，我们采用了一项5次试验的社会记忆任务，来研究6个月大的TgF344-AD雄性和雌性大鼠的早期社会认知缺陷。我们计算了PV+中间神经元的数量，并在海马CA2区（对社会信息处理至关重要的区域）的社交互动过程中记录了局部场电位。我们的结果显示，TgF344-AD雄性和雌性大鼠的社会兴趣和新奇偏好降低。然而，仅在雌性大鼠中观察到PV+中间神经元数量减少，且特定于CA2区域。电生理记录显示，在直接社交互动期间，CA2区的θ-γ相位-振幅耦合降低。我们得出结论，TgF344-AD大鼠的早期AD伴有社会认知缺陷，并且可能与海马CA2区的PV+中间神经元和脑振荡功能障碍有关。
