School of Biological Sciences, National Institute of Science Education and Research (NISER), HBNI, PO - Bhimpur-Padanpur, Jatni - 752050, Dist. -Khurda, Odisha, India; Centre for Interdisciplinary Science (CIS), National Institute of Science Education and Research (NISER), HBNI, PO - Bhimpur-Padanpur, Jatni - 752050, Dist. -Khurda, Odisha, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India.
School of Biological Sciences, National Institute of Science Education and Research (NISER), HBNI, PO - Bhimpur-Padanpur, Jatni - 752050, Dist. -Khurda, Odisha, India; Centre for Interdisciplinary Science (CIS), National Institute of Science Education and Research (NISER), HBNI, PO - Bhimpur-Padanpur, Jatni - 752050, Dist. -Khurda, Odisha, India.
Neuroscience. 2023 May 21;519:73-89. doi: 10.1016/j.neuroscience.2023.03.016. Epub 2023 Mar 24.
The circadian clock can coordinate, regulate and predict physiology and behavior in response to the standard light-dark (LD: 12 h light and 12 h dark) cycle. If we alter the LD cycle by exposing mice to constant darkness (DD: 00 h light and 24 h dark), it can perturb behavior, the brain, and associated physiological parameters. The length of DD exposure and the sex of experimental animals are crucial variables that could alter the impact of DD on the brain, behavior, and physiology, which have not yet been explored. We exposed mice to DD for three and five weeks and studied their impact on (1) behavior, (2) hormones, (3) the prefrontal cortex, and (4) metabolites in male and female mice. We also studied the effect of three weeks of standard light-dark cycle restoration after five weeks of DD on the parameters mentioned above. We found that DD exposure was associated with anxiety-like behavior, increased corticosterone and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), downregulated neurotrophins (BDNF and NGF), and altered metabolites profile in a duration of DD exposure and sex-dependent manner. Females showed a more robust adaptation than males under DD exposure. Three weeks of restoration was adequate to establish homeostasis in both sexes. To the best of our knowledge, this study is the first of its kind to look at how DD exposure impacts physiology and behavior as a function of sex- and time. These findings would have translational value and may help in establishing sex-specific interventions for addressing DD-related psychological issues.
生物钟可以协调、调节和预测生理和行为，以适应标准的明暗（LD：12 小时光照和 12 小时黑暗）周期。如果我们通过让老鼠暴露在持续的黑暗中（DD：00 小时光照和 24 小时黑暗）来改变 LD 周期，它会扰乱行为、大脑和相关的生理参数。DD 暴露的时间长度和实验动物的性别是关键变量，它们可能会改变 DD 对大脑、行为和生理的影响，但尚未得到探索。我们让老鼠暴露在 DD 中 3 周和 5 周，研究它们对（1）行为、（2）激素、（3）前额叶皮层和（4）雄性和雌性老鼠代谢物的影响。我们还研究了在 DD 后 5 周恢复 3 周标准明暗周期对上述参数的影响。我们发现，DD 暴露与焦虑样行为、皮质酮和促炎细胞因子（TNF-α、IL-6 和 IL-1β）增加、神经营养因子（BDNF 和 NGF）下调以及代谢物谱改变有关，这些变化与 DD 暴露时间和性别有关。与雄性相比，雌性在 DD 暴露下表现出更强的适应性。3 周的恢复足以在两性中建立体内平衡。据我们所知，这项研究首次观察了 DD 暴露如何根据性别和时间影响生理和行为。这些发现具有转化价值，并可能有助于确定针对 DD 相关心理问题的性别特异性干预措施。
