Drummond Katherine D, Waring Michelle L, Faulkner Geoffrey J, Blewitt Marnie E, Perry Christina J, Kim Jee Hyun
Mental Health Theme, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3052, Australia.
Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, 3052, Australia.
Neurobiol Stress. 2021 Jul 13;15:100367. doi: 10.1016/j.ynstr.2021.100367. eCollection 2021 Nov.
Impaired extinction of conditioned fear is associated with anxiety disorders. Common lifestyle factors, like isolation stress and exercise, may alter the ability to extinguish fear. However, the effect of and interplay between these factors on adolescent fear extinction, and the relevant underlying neural mechanisms are unknown. Here we examined the effects of periadolescent social isolation and physical activity on adolescent fear extinction in rats and explored neurogenesis as a potential mechanism. Isolation stress impaired extinction recall in male adolescents, an effect prevented by exercise. Extinction recall in female adolescents was unaffected by isolation stress. However, exercise disrupted extinction recall in isolated females. Extinction recall in isolated females was positively correlated to the number of immature neurons in the ventral hippocampus, suggesting that exercise affected extinction recall via neurogenesis in females. Pharmacologically suppressing cellular proliferation in isolated adolescents using temozolomide blocked the effect of exercise on extinction recall in both sexes. Together, these findings highlight sex-specific outcomes of isolation stress and exercise on adolescent brain and behavior, and highlights neurogenesis as a potential mechanism underlying lifestyle effects on adolescent fear extinction.
条件性恐惧消退受损与焦虑症有关。常见的生活方式因素，如隔离应激和运动，可能会改变恐惧消退的能力。然而，这些因素对青少年恐惧消退的影响及其相互作用，以及相关的潜在神经机制尚不清楚。在这里，我们研究了青春期前后的社会隔离和体育活动对大鼠青少年恐惧消退的影响，并探讨了神经发生作为一种潜在机制。隔离应激损害了雄性青少年的消退记忆，而运动可预防这种影响。雌性青少年的消退记忆不受隔离应激的影响。然而，运动扰乱了隔离雌性的消退记忆。隔离雌性的消退记忆与腹侧海马中未成熟神经元的数量呈正相关，这表明运动通过雌性的神经发生影响消退记忆。使用替莫唑胺在隔离青少年中药理抑制细胞增殖，阻断了运动对两性消退记忆的影响。总之，这些发现突出了隔离应激和运动对青少年大脑和行为的性别特异性结果，并突出了神经发生作为生活方式对青少年恐惧消退影响的潜在机制。
