Zimmermann Annelie, Priebe Julia, Rupprecht Hanna, Lang Stephan, Haberland Fabienne, Schuster Katharina, Staffeld Anna, Berger Christoph, Zhu Hang, Dück Alexander, Kölch Michael, Frintrop Linda
Institute of Anatomy, Rostock University Medical Center, Rostock, Germany.
Department of Psychiatry, Neurology, Psychosomatics, and Psychotherapy in Childhood and Adolescence, Rostock University Medical Center, Rostock, Germany.
Int J Eat Disord. 2025 Apr;58(4):756-769. doi: 10.1002/eat.24379. Epub 2025 Jan 21.
Anorexia nervosa (AN) is an eating disorder characterized by severe weight loss and associated with hyperactivity and circadian rhythm disruption. However, the cellular basis of circadian rhythm disruption is poorly understood. Glial cells in the suprachiasmatic nucleus (SCN), the principal circadian pacemaker, are involved in regulating circadian rhythms. We hypothesize that the circadian rhythm disruption in AN patients is associated with glial cell changes in the SCN.
In the starvation-induced hyperactivity mouse model, mice had free access to a running wheel and received a restricted amount of food once a day, until a 25% body weight loss was reached and maintained their weight loss for two weeks. This was followed by a refeeding phase. Different daily periods of running wheel activity were defined, such as food anticipatory activity up to 4 h before feeding. Circadian rhythmicity was analyzed using the cosinor method. Gene expression was evaluated using real-time polymerase chain reaction. Immunohistochemistry was used to quantify astrocytes, microglia, and oligodendrocytes.
Starvation induced changes in circadian rhythm, as indicated by changes in cosinor-based characteristics. Refeeding reversed these effects. Additionally, there was an increase in cryptochrome circadian regulator 1 expression and a decrease in the density of astrocytes and oligodendrocytes in the SCN after chronic starvation.
Starvation-induced alterations in circadian rhythms are associated with molecular, and cellular changes in the hypothalamus. Reduced astrocytes and oligodendrocytes in the SCN in a mouse model of AN suggest that glial pathophysiology may play a role in circadian rhythm disruption.
神经性厌食症（AN）是一种以严重体重减轻为特征的饮食失调症，与多动和昼夜节律紊乱有关。然而，昼夜节律紊乱的细胞基础尚不清楚。视交叉上核（SCN）作为主要的昼夜节律起搏器，其中的神经胶质细胞参与调节昼夜节律。我们假设AN患者的昼夜节律紊乱与SCN中的神经胶质细胞变化有关。
在饥饿诱导的多动小鼠模型中，小鼠可自由使用跑轮，每天给予限量食物，直至体重减轻25%并维持两周体重减轻状态。随后进入再喂养阶段。定义了不同的每日跑轮活动时间段，如进食前长达4小时的食物预期活动。使用余弦分析法分析昼夜节律性。使用实时聚合酶链反应评估基因表达。采用免疫组织化学法对星形胶质细胞、小胶质细胞和少突胶质细胞进行定量。
如基于余弦分析的特征变化所示，饥饿诱导了昼夜节律的改变。再喂养逆转了这些影响。此外，长期饥饿后，SCN中隐花色素昼夜节律调节因子1的表达增加，星形胶质细胞和少突胶质细胞的密度降低。
饥饿诱导的昼夜节律改变与下丘脑中的分子和细胞变化有关。AN小鼠模型中SCN中星形胶质细胞和少突胶质细胞减少表明，神经胶质病理生理学可能在昼夜节律紊乱中起作用。
