Chakraborty Prabahan, Dromard Yann, André Emilie M, Dedin Maheva, Arango-Lievano Margarita, Raner Ana, Besnard Antoine, Silva Thamyris Santos, Helbling Jean-Christophe, Ferreira Guillaume, Challet Etienne, Moisan Marie-Pierre, Jeanneteau Freddy
Institut de Génomique Fonctionnelle, University of Montpellier, INSERM, CNRS, 141 rue de la Cardonille, 34094, Montpellier, France; Department of Genetic Engineering, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, 60203, India.
Institut de Génomique Fonctionnelle, University of Montpellier, INSERM, CNRS, 141 rue de la Cardonille, 34094, Montpellier, France.
EBioMedicine. 2025 Jun 16;117:105783. doi: 10.1016/j.ebiom.2025.105783.
Highly caloric food consumed around the clock perturbs the metabolism and cognitive functioning. We hypothesised that obesogenic food could alter neuronal representations of memory depending on the feeding-fasting cycle.
We tracked memory performance, dendritic spine dynamics and neuronal representations of memory in C57Bl6J mice fed obesogenic food ad libitum from peri-adolescence. We aimed to correct energy rich diet-induced plasticity deficits and cognitive impairment with time-restricted feeding in males and females. We further used chemogenetics, pharmacology and knock-in mice to investigate functional correlates underlying diet-induced neurocognitive impairments.
We found that changes in the feeding-fasting cycle reverted the effects of ad libitum obesogenic food on memory impairment in both sexes (n = 55, p = 0.003). Concurrently, it also corrected the increased dendritic spine maintenance and neuroactivity in hippocampus and the decreased spine maintenance and activity in parietal cortex (n = 48, p < 0.005). Bi-directional effects in cortex and hippocampus mediated by glucocorticoid signalling are causal to behavioural changes (n = 91, p = 0.0008), and scaling hippocampal with cortical activities restored memory in mice fed obesogenic food (n = 44, p = 0.02).
These results indicate that meal scheduling is a promising approach to confront glucocorticoid signalling bias and memory deficits caused by obesogenic food.
Agence Nationale de la Recherche (ANR-21-CE14-0086), Fondation pour la Recherche sur le Cerveau (FRC).
全天候食用高热量食物会扰乱新陈代谢和认知功能。我们假设致肥胖食物可能会根据进食-禁食周期改变记忆的神经元表征。
我们追踪了从青春期前后开始随意喂食致肥胖食物的C57Bl6J小鼠的记忆表现、树突棘动态变化和记忆的神经元表征。我们旨在通过对雄性和雌性小鼠进行限时喂养来纠正高能量饮食引起的可塑性缺陷和认知障碍。我们还使用化学遗传学、药理学和基因敲入小鼠来研究饮食诱导的神经认知障碍背后的功能相关性。
我们发现，进食-禁食周期的变化逆转了随意喂食致肥胖食物对两性记忆损害的影响（n = 55，p = 0.003）。同时，它还纠正了海马体中增加的树突棘维持和神经活动以及顶叶皮质中减少的树突棘维持和活动（n = 48，p < 0.005）。由糖皮质激素信号介导的皮质和海马体中的双向作用是行为变化的原因（n = 91，p = 0.0008），并且使海马体与皮质活动相匹配可恢复喂食致肥胖食物小鼠的记忆（n = 44，p = 0.02）。
这些结果表明，饮食安排是应对由致肥胖食物引起的糖皮质激素信号偏差和记忆缺陷的一种有前景的方法。
法国国家研究机构（ANR-21-CE14-0086），大脑研究基金会（FRC）。
