Bouteldja Ahmed A, Marceau Lianne A, Srivastava Lalit K, Cermakian Nicolas
Douglas Mental Health University Institute, Montréal, Québec, Canada.
Integrated Program in Neuroscience, McGill University, Montréal, Québec, Canada.
Eur J Neurosci. 2025 May;61(9):e70134. doi: 10.1111/ejn.70134.
Schizophrenia is believed to arise because of the interaction of early abnormal neurodevelopment with environmental insults during key developmental stages later in life. Furthermore, disrupted circadian rhythms are reported in patients, and circadian disruption is associated with increased symptom severity, hinting at its role as a risk factor. Using the neonatal ventral hippocampal lesion mouse model, we aimed to assess the interaction between disrupted ventral hippocampal development with circadian disruption during adolescence in affecting behavior in male and female C57BL/6N mice. After conducting a series of behavioral tests, we found that the neonatal ventral hippocampal lesion and chronic jet lag during adolescence synergistically led to increased anxiety-like behavior in males. In females, the lesion prevented increased social preference caused by chronic jet lag and led to increased anxiety-like behavior. Mice were then moved to running wheel cages to measure their locomotor activity rhythms. We found that the lesioned male mice exposed to chronic jet lag exhibited fragmented rhythms under constant darkness. Moreover, lesioned male and female mice, especially those exposed to chronic jet lag, had reduced activity counts under constant light. These findings highlight that the interaction of abnormal neurodevelopment in areas relevant to schizophrenia with circadian disruption during adolescence results in lasting behavioral changes in a sex-dependent manner in mice.
精神分裂症被认为是由于早期异常神经发育与生命后期关键发育阶段的环境损伤相互作用而产生的。此外，据报道患者存在昼夜节律紊乱，且昼夜节律紊乱与症状严重程度增加有关，这暗示了其作为一个风险因素的作用。我们使用新生小鼠腹侧海马损伤模型，旨在评估青春期腹侧海马发育紊乱与昼夜节律紊乱之间的相互作用对雄性和雌性C57BL/6N小鼠行为的影响。在进行了一系列行为测试后，我们发现新生小鼠腹侧海马损伤与青春期慢性时差反应协同导致雄性小鼠焦虑样行为增加。在雌性小鼠中，损伤阻止了慢性时差反应引起的社会偏好增加，并导致焦虑样行为增加。然后将小鼠转移到跑轮笼中以测量其运动活动节律。我们发现，暴露于慢性时差反应的损伤雄性小鼠在持续黑暗条件下表现出节律紊乱。此外，损伤的雄性和雌性小鼠，尤其是那些暴露于慢性时差反应的小鼠，在持续光照下活动计数减少。这些发现突出表明，与精神分裂症相关区域的异常神经发育与青春期昼夜节律紊乱之间的相互作用，以性别依赖的方式在小鼠中导致持久的行为变化。
