Chanda Kaushik, Carter Jackson P, Nishizono Hirofumi, Raveendra Bindu L, Brantley Alicia, Grinman Eddie, Espadas Isabel, Lozano-Villada Sebastian, Wingfield Jenna Lynne, Wagner Grace, Peterson Amy, Yasuda Ryohei, Puthanveettil Sathyanarayanan V
Department of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Max Planck Florida Institute, 1 Max Planck Way, Jupiter, FL 33458, USA.
iScience. 2025 Jul 5;28(8):113070. doi: 10.1016/j.isci.2025.113070. eCollection 2025 Aug 15.
Activity-dependent neuronal changes are critical for learning and memory, but the role of long noncoding RNAs (lncRNAs) in these processes is under active investigation. In this study we investigated ADEPTR, a dendritically localized, cAMP-modulated lncRNA essential for synapse morphology. Using two mouse models-one with ADEPTR deletion (L-ADEPTR) and another lacking its protein interaction domain (S-ADEPTR)-we examined sex-specific effects on behavior and neuronal architecture. Behavioral tests showed reduced anxiety in S-ADEPTR adult male mice, with no learning or memory deficits in either model. Neuronal cultures and brain samples from various developmental stages revealed morphological impairments in both sexes. Notably, L-ADEPTR female mice had fewer thin spines in the hippocampal CA1 region at postnatal day 42. Despite these structural deficits, increased expression of plasticity-related genes BDNF and cFOS in the cortex and hippocampus suggests compensatory mechanisms preserve cognitive function. These findings highlight a sex-specific role for ADEPTR in regulating neuronal structure and anxiety-related behaviors.
依赖活动的神经元变化对学习和记忆至关重要，但长链非编码RNA（lncRNA）在这些过程中的作用正在积极研究中。在本研究中，我们研究了ADEPTR，一种定位于树突、受cAMP调节的lncRNA，对突触形态至关重要。使用两种小鼠模型——一种是ADEPTR缺失模型（L-ADEPTR），另一种是缺乏其蛋白质相互作用结构域的模型（S-ADEPTR）——我们研究了对行为和神经元结构的性别特异性影响。行为测试显示，S-ADEPTR成年雄性小鼠的焦虑减少，两种模型均无学习或记忆缺陷。来自不同发育阶段的神经元培养物和脑样本显示两性均有形态学损伤。值得注意的是，L-ADEPTR雌性小鼠在出生后第42天海马CA1区的细棘较少。尽管存在这些结构缺陷，但皮质和海马中可塑性相关基因BDNF和cFOS的表达增加表明补偿机制维持了认知功能。这些发现突出了ADEPTR在调节神经元结构和焦虑相关行为中的性别特异性作用。
