Li Yong, Dong Yan, Yang Luodan, Tucker Lorelei, Zong Xuemei, Brann Darrell, Hamblin Michael R, Vazdarjanova Almira, Zhang Quanguang
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa.
Mol Psychiatry. 2021 Nov;26(11):6666-6679. doi: 10.1038/s41380-021-01088-z. Epub 2021 Apr 15.
A precise fear memory encoding a traumatic event enables an individual to avoid danger and identify safety. An impaired fear memory (contextual amnesia), however, puts the individual at risk of developing posttraumatic stress disorder (PTSD) due to the inability to identify a safe context when encountering trauma-associated cues later in life. Although it is gaining attention that contextual amnesia is a critical etiologic factor for PTSD, there is no treatment currently available that can reverse contextual amnesia, and whether such treatment can prevent the development of PTSD is unknown. Here, we report that (I) a single dose of transcranial photobiomodulation (PBM) applied immediately after tone fear conditioning can reverse contextual amnesia. PBM treatment preserved an appropriately high level of contextual fear memory in rats revisiting the "dangerous" context, while control rats displayed memory impairment. (II) A single dose of PBM applied after memory recall can reduce contextual fear during both contextual and cued memory testing. (III) In a model of complex PTSD with repeated trauma, rats given early PBM interventions efficiently discriminated safety from danger during cued memory testing and, importantly, these rats did not develop PTSD-like symptoms and comorbidities. (IV) Finally, we report that fear extinction was facilitated when PBM was applied in the early intervention window of memory consolidation. Our results demonstrate that PBM treatment applied immediately after a traumatic event or its memory recall can protect contextual fear memory and prevent the development of PTSD-like psychopathological fear in rats.
精确编码创伤性事件的恐惧记忆能使个体避免危险并识别安全环境。然而，恐惧记忆受损（情境性失忆）会使个体在日后生活中遇到与创伤相关的线索时，因无法识别安全情境而有患创伤后应激障碍（PTSD）的风险。尽管情境性失忆作为PTSD的关键病因因素正日益受到关注，但目前尚无能够逆转情境性失忆的治疗方法，而且这种治疗能否预防PTSD的发生也尚不清楚。在此，我们报告：（I）在音调恐惧条件反射后立即给予单次经颅光生物调节（PBM）可逆转情境性失忆。PBM治疗使再次进入“危险”情境的大鼠保持了适当高水平的情境恐惧记忆，而对照大鼠则表现出记忆受损。（II）在记忆回忆后给予单次PBM可在情境性和线索性记忆测试期间减轻情境恐惧。（III）在重复创伤的复杂性PTSD模型中，早期接受PBM干预的大鼠在线索性记忆测试中能有效区分安全与危险，重要的是，这些大鼠未出现PTSD样症状和共病。（IV）最后，我们报告在记忆巩固的早期干预窗口应用PBM时，恐惧消退得到促进。我们的结果表明，在创伤事件或其记忆回忆后立即应用PBM治疗可保护情境恐惧记忆，并预防大鼠出现PTSD样心理病理性恐惧。
