This study aimed to assess the effects of cotinine on age-induced memory and learning impairment and related downstream pathways in mice. Thirty aged (18-month old) and 10 young mice (8-week old) were randomly divided into 4 groups (n = 10 each) and subjected to cotinine at 5 mg/kg dose and/or methyllycaconitine (MLA) at 1 mg/kg, i.p. dose (α₇ nAChRs antagonist) for 4 weeks. Morris water maze (MWM) and novel object recognition (NOR) tasks were used to assess spatial and recognition learning and memories of the mice, respectively. Levels of oxidative stress, apoptosis, neuroinflammation, and structural synaptic plasticity, and also neurotrophic factors and α₇ nAChRs were assessed in the hippocampus using either ELISA or Western blotting. Aging was associated with learning and memory disabilities and dysregulation of the assessed pathways in the hippocampus of mice. Chronic cotinine treatment improved learning and memory in aged animals, indicated by decreased latency time, and increased time spent in the target quadrant and discrimination index (DI) in the MWM and NOR tasks. Also, chronic cotinine injection increased total antioxidant capacity (TAC), SOD and GSH-px activity, PSD-95, GAP-43, SYN, brain-derived neurotrophic factor, and neural growth factor levels and decreased malondialdehyde, TNF-α, and IL-1β in the hippocampus of aged mice. Conversely, MLA treatment reversed most of the mentioned effects via the blockade of α₇ nAChRs. Cotinine improves age-induced memory and learning impairment via its modulatory effects on α₇ nAChRs and subsequent activation/deactivation of the mentioned pathways in the hippocampus of aged mice.

本研究旨在评估可替宁对小鼠年龄诱导的记忆和学习障碍及相关下游通路的影响。将 30 只（18 个月大）和 10 只幼鼠（8 周大）随机分为 4 组（每组 n = 10），并接受 5 mg/kg 剂量的可替宁和/或 1 mg 甲基可替宁 (MLA) /kg，ip 剂量（α ₇ nAChRs 拮抗剂），持续 4 周。Morris水迷宫（MWM）和新物体识别（NOR）任务分别用于评估小鼠的空间和识别学习和记忆。氧化应激水平、细胞凋亡、神经炎症和结构突触可塑性，以及神经营养因子和 α ₇使用 ELISA 或蛋白质印迹法在海马中评估 nAChR。衰老与学习和记忆障碍以及小鼠海马体中评估通路的失调有关。慢性可替宁治疗改善了老年动物的学习和记忆，这表现为潜伏时间减少，MWM 和 NOR 任务中在目标象限和辨别指数 (DI) 上花费的时间增加。此外，长期注射可替宁可增加总抗氧化能力 (TAC)、SOD 和 GSH-px 活性、PSD-95、GAP-43、SYN、脑源性神经营养因子和神经生长因子水平，并降低丙二醛、TNF-α 和老年小鼠海马体中的 IL-1β。相反，MLA 治疗通过阻断 α ₇逆转了大部分提到的影响nAChR。可替宁通过其对 α ₇ nAChRs 的调节作用以及随后激活/失活老年小鼠海马体中提到的通路来改善年龄引起的记忆和学习障碍。