Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Institute of Pharmacy, Freie Universität Berlin, 14195 Berlin, Germany.
Cells. 2023 May 10;12(10):1355. doi: 10.3390/cells12101355.
Currently, there are no animal models for studying both specific social fear and social fear with comorbidities. Here, we investigated whether social fear conditioning (SFC), an animal model with face, predictive and construct validity for social anxiety disorder (SAD), leads to the development of comorbidities at a later stage over the course of the disease and how this affects the brain sphingolipid metabolism. SFC altered both the emotional behavior and the brain sphingolipid metabolism in a time-point-dependent manner. While social fear was not accompanied by changes in non-social anxiety-like and depressive-like behavior for at least two to three weeks, a comorbid depressive-like behavior developed five weeks after SFC. These different pathologies were accompanied by different alterations in the brain sphingolipid metabolism. Specific social fear was accompanied by increased activity of ceramidases in the ventral hippocampus and ventral mesencephalon and by small changes in sphingolipid levels in the dorsal hippocampus. Social fear with comorbid depression, however, altered the activity of sphingomyelinases and ceramidases as well as the sphingolipid levels and sphingolipid ratios in most of the investigated brain regions. This suggests that changes in the brain sphingolipid metabolism might be related to the short- and long-term pathophysiology of SAD.
目前，尚无用于研究特定社交恐惧和伴有共病的社交恐惧的动物模型。在这里，我们研究了社交恐惧条件反射（SFC）——一种具有社交焦虑障碍（SAD）面部、预测和构建效度的动物模型——是否会在疾病过程中的后期发展出共病，以及这如何影响大脑神经鞘脂代谢。SFC 以时间依赖的方式改变了情绪行为和大脑神经鞘脂代谢。虽然社交恐惧至少在两到三周内没有伴随非社交焦虑样和抑郁样行为的变化，但 SFC 五周后出现了共病性抑郁样行为。这些不同的病理变化伴随着大脑神经鞘脂代谢的不同改变。特定的社交恐惧伴随着腹侧海马体和腹侧中脑神经鞘脂代谢中神经酰胺酶活性的增加，以及背侧海马体神经鞘脂水平的微小变化。然而，伴有共病抑郁的社交恐惧改变了大多数研究脑区的鞘磷脂酶和神经酰胺酶活性以及神经鞘脂水平和神经鞘脂比值。这表明，大脑神经鞘脂代谢的变化可能与 SAD 的短期和长期病理生理学有关。
