Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Int J Mol Sci. 2022 Mar 21;23(6):3398. doi: 10.3390/ijms23063398.
Acid sphingomyelinase (ASM) regulates a variety of physiological processes and plays an important role in emotional behavior. The role of ASM in fear-related behavior has not been investigated so far. Using transgenic mice overexpressing ASM (ASMtg) and ASM deficient mice, we studied whether ASM regulates fear learning and expression of cued and contextual fear in a classical fear conditioning paradigm, a model used to investigate specific attributes of post-traumatic stress disorder (PTSD). We show that ASM does not affect fear learning as both ASMtg and ASM deficient mice display unaltered fear conditioning when compared to wild-type littermates. However, ASM regulates the expression of contextual fear in a sex-specific manner. While ASM overexpression enhances the expression of contextual fear in both male and female mice, ASM deficiency reduces the expression of contextual fear specifically in male mice. The expression of cued fear, however, is not regulated by ASM as ASMtg and ASM deficient mice display similar tone-elicited freezing levels. This study shows that ASM modulates the expression of contextual fear but not of cued fear in a sex-specific manner and adds a novel piece of information regarding the involvement of ASM in hippocampal-dependent aversive memory.
酸性鞘磷脂酶 (ASM) 调节多种生理过程，并在情绪行为中发挥重要作用。ASM 与恐惧相关行为的关系尚未得到研究。使用过表达 ASM 的转基因小鼠 (ASMtg) 和 ASM 缺陷小鼠，我们研究了 ASM 是否调节经典恐惧条件反射范式中的恐惧学习和条件恐惧表达，该模型用于研究创伤后应激障碍 (PTSD) 的特定属性。我们发现 ASM 不会影响恐惧学习，因为与野生型同窝仔相比，ASMtg 和 ASM 缺陷小鼠的恐惧条件反射均未改变。然而，ASM 以性别特异性的方式调节情境恐惧的表达。虽然 ASM 过表达增强了雄性和雌性小鼠的情境恐惧表达，但 ASM 缺陷特异性地降低了雄性小鼠的情境恐惧表达。然而，ASM 不调节条件恐惧的表达，因为 ASMtg 和 ASM 缺陷小鼠显示出相似的音调引发的冻结水平。这项研究表明，ASM 以性别特异性的方式调节情境恐惧的表达，但不调节条件恐惧的表达，并为 ASM 参与海马依赖性厌恶记忆提供了新的信息。
