Excessive levels of GABA released by astrocytes impair the brain’s ability to extinguish fear responses in PTSD, but a newly identified drug target offers promising hope for treatment.
由星形胶质细胞释放的过量GABA会削弱大脑消除PTSD恐惧反应的能力，但一个新发现的药物靶点为治疗带来了有希望的前景。
Many people with post-traumatic stress disorder (PTSD) continue to relive painful memories long after the actual threat is gone.
许多患有创伤后应激障碍（PTSD）的人在实际威胁消失后仍会反复重现痛苦记忆。
Their brains seem unable to let go of fear, a phenomenon that has long puzzled scientists and made effective treatment difficult.
他们的大脑似乎无法摆脱恐惧，这种现象长期以来困扰着科学家，并使得有效治疗变得困难。
Current medications that target serotonin receptors often provide only limited relief, and usually help just a fraction of those affected.
目前靶向血清素受体的药物往往只能带来有限的缓解，且通常只对部分患者有效。
Now, researchers from the Institute for Basic Science (IBS) and Ewha Womans University have identified a previously unknown brain process that may be responsible for this persistent fear response.
现在，韩国基础科学研究院（IBS）和梨花女子大学的研究人员发现了一种此前未知的大脑机制，可能是导致这种持续性恐惧反应的原因。
They have also found a potential treatment that could change how PTSD is managed.
他们还发现了一种可能改变PTSD治疗方式的潜在疗法。
The study, led by Dr. C. Justin LEE from the IBS Center for Cognition and Sociality and Professor LYOO In Kyoon from Ewha Womans University, discovered that astrocytes (star-shaped support cells in the brain) can produce too much GABA (gamma-aminobutyric acid).
这项研究由IBS认知与社会性研究中心的李贞镇博士与梨花女子大学的柳仁均教授领导，发现星形胶质细胞（一种星状的脑部支持细胞）可以产生过量的GABA（γ-氨基丁酸）。
This excess GABA interferes with the brain’s ability to suppress fear-related memories, a key difficulty for people with PTSD.
这种GABA过量会干扰大脑压制与恐惧相关记忆的能力，这是PTSD患者面临的一个关键难题。
Importantly, the team tested a drug called KDS2010 that crosses the blood-brain barrier and specifically blocks the monoamine oxidase B enzyme, which drives this abnormal GABA production.
重要的是，研究团队测试了一种名为KDS2010的药物，它能穿过血脑屏障，并特异性地抑制促使这种异常GABA产生的单胺氧化酶B（MAO-B）酶。
In mouse models, the drug was able to reduce PTSD-like symptoms.
在小鼠模型中，该药物能够减轻类似PTSD的症状。
KDS2010 has already completed Phase 1 human safety trials, positioning it as a promising option for future PTSD treatment.
KDS2010已完成第一阶段人体安全性试验，使其成为未来PTSD治疗的有前景选择。
PTSD remains difficult to treat, with current medications targeting serotonin pathways providing limited relief for many patients.
PTSD仍然难以治疗，目前针对血清素通路的药物对许多患者而言效果有限。
The new study focused on the medial prefrontal cortex (mPFC), a region of the brain critical for regulating fear, and found that PTSD patients had unusually high levels of GABA and reduced cerebral blood flow in this area.
这项新研究聚焦于内侧前额叶皮质（mPFC），这是大脑中调节恐惧的重要区域，研究发现PTSD患者在该区域的GABA水平异常升高，脑血流量减少。
These findings emerged from brain imaging studies of more than 380 participants.
这些发现来源于对380多名参与者的大脑影像研究。
Importantly, GABA levels decreased in patients who showed clinical improvement, pointing to the chemical’s central role in recovery.
重要的是，那些临床症状改善的患者体内GABA水平有所下降，这表明这种化学物质在康复中起着核心作用。
To uncover the origin of this excess GABA, the researchers examined postmortem human brain tissue and used PTSD-like mouse models.
为揭示过量GABA的来源，研究人员检查了人类死亡后的脑组织，并使用了类PTSD的小鼠模型。
They discovered that astrocytes, not neurons, were producing abnormal amounts of GABA via the enzyme monoamine oxidase B (MAOB).
他们发现，产生异常数量GABA的不是神经元，而是星形胶质细胞，这种过程依赖于一种叫做单胺氧化酶B（MAOB）的酶。
This astrocyte-derived GABA impaired neural activity, blocking the brain’s ability to forget traumatic memories.
这种由星形胶质细胞生成的GABA损害了神经活动，阻碍了大脑遗忘创伤性记忆的能力。
When the researchers administered KDS2010, a highly selective, reversible MAOB inhibitor developed at IBS, the mice showed normalized brain activity and were able to extinguish fear responses.
当研究人员使用IBS开发的高度选择性、可逆的MAOB抑制剂KDS2010进行干预时，小鼠的大脑活动恢复正常，并能消除恐惧反应。
The drug reduced GABA levels, restored blood flow in the mPFC, and re-enabled memory extinction mechanisms.
该药物降低了GABA水平，恢复了内侧前额叶皮层（mPFC）的血流，并重新激活了记忆消除机制。
The study thus confirms astrocytic MAOB as a central driver of PTSD symptoms, and MAOB inhibition as a viable therapeutic path.
这项研究由此确认了星形胶质细胞的MAOB是PTSD症状的核心驱动因素，而抑制MAOB是一种可行的治疗途径。
A Reverse Translational Approach
反向转化研究方法
A major challenge of the study was linking clinical findings in humans with cellular mechanisms in the lab.
该研究的一个主要挑战是将人类的临床发现与实验室中的细胞机制相联系。
The researchers addressed this by applying a “reverse translational” strategy: they began with clinical brain scans and moved backward to identify the cellular source of dysfunction, then confirmed the mechanism and tested drug effects in animal models.
研究人员采用了“反向转化”策略来应对这一挑战：他们从临床脑部扫描开始，反向追踪功能障碍的细胞来源，然后确认机制，并在动物模型中测试药物效果。
This approach led to a new understanding of how glial cells — long thought to be passive — actively shape psychiatric symptoms.
这种方法带来了一个全新的认识：长期被认为是被动的胶质细胞实际上在精神疾病症状的形成中起着积极作用。
“This study is the first to identify astrocyte-derived GABA as a key pathological driver of fear extinction deficit in PTSD,” said Dr. WON Woojin, a postdoctoral researcher and co-first author of the study.
“本研究首次发现由星形胶质细胞产生的GABA是PTSD中恐惧消除障碍的关键病理驱动因素，”该研究的共同第一作者、博士后研究员WON Woojin博士表示。
“Our findings not only uncover a novel astrocyte-based mechanism underlying PTSD, but also provide preclinical evidence for a new therapeutic approach using an MAOB inhibitor.”
“我们的发现不仅揭示了PTSD的一种全新、以星形胶质细胞为基础的机制，还提供了使用MAOB抑制剂的新疗法的临床前证据。”
Director C. Justin LEE, who led the study, emphasized that “This work represents a successful example of reverse translational research, where clinical findings in human guided the discovery of underlying mechanisms in animal models.
该研究负责人C. Justin LEE主任强调：“这项工作是反向转化研究的一个成功案例，其中人类的临床发现指导了动物模型中潜在机制的发现。
By identifying astrocytic GABA as a pathological driver in PTSD and targeting it via MAOB inhibition, the study opens a completely new therapeutic paradigm not only for PTSD but also for other neuropsychiatric disorders such as panic disorder, depression, and schizophrenia.”
通过确认星形胶质细胞产生的GABA是PTSD的病理驱动因素，并通过抑制MAOB来进行干预，这项研究不仅为PTSD，也为恐慌障碍、抑郁症和精神分裂症等其他神经精神疾病开辟了一种全新的治疗模式。
The researchers plan to further investigate astrocyte-targeted therapies for various neuropsychiatric disorders.
研究人员计划进一步探索针对星形胶质细胞的多种神经精神疾病治疗方法。
With KDS2010 currently undergoing Phase 2 clinical trials, this discovery may soon lead to new options for patients whose symptoms have not responded to conventional treatments.
随着KDS2010正在进行第二阶段临床试验，这一发现可能很快为那些对常规治疗无效的患者提供新的选择。
精选词汇
astrocyte /ˈæstrəˌsaɪt/ n. a type of glial cell in the brain that supports neurons
星形胶质细胞：大脑中的一种支持性胶质细胞
例句：Astrocytes help regulate neurotransmitters and maintain the blood-brain barrier.
星形胶质细胞有助于调节神经递质并维持血脑屏障。
extinguish /ɪkˈstɪŋɡwɪʃ/ v. to put an end to (an emotion, idea, etc.)
熄灭，消除（情感、想法等）
例句：Therapy helped extinguish his irrational fears.
治疗帮助他消除了非理性的恐惧。
cadence /ˈkeɪdəns/ n. the rhythm or number of steps per minute
节奏；步频
例句：Increasing walking cadence has been linked to improved cardiovascular health.
提高步频已被证实与心血管健康改善相关。
impair /ɪmˈper/ v. to weaken or damage
削弱，损害
例句：Alcohol can impair your ability to make decisions.
酒精会削弱你的判断力。
interfere /ˌɪntərˈfɪr/ v. to prevent something from happening properly
干扰；妨碍
例句：Loud noise interferes with my concentration.
噪音会干扰我集中注意力。
receptor /rɪˈsɛptər/ n. a structure on a cell that receives signals
受体
例句：Serotonin receptors are common targets in psychiatric medications.
血清素受体是精神类药物常见的靶点。
let go of /phr./ to release or stop holding
放下，释怀
例句：It’s hard for some patients to let go of traumatic memories.
有些患者很难放下创伤性记忆。
persistent /pərˈsɪstənt/ adj. continuing despite difficulty
持续的；顽固的
例句：Persistent symptoms may indicate a chronic condition.
持续的症状可能提示慢性病。
suppress /səˈprɛs/ v. to hold back or stop
抑制；压制
例句：The medication helps suppress anxiety.
该药物有助于抑制焦虑。
monoamine oxidase /ˌmɒnoʊˈæmin ˈɑksɪˌdeɪs/ n. an enzyme that breaks down neurotransmitters
单胺氧化酶
例句：Inhibiting monoamine oxidase can increase serotonin levels.
抑制单胺氧化酶可提高血清素水平。
barrier /ˈbæriər/ n. something that blocks or separates
屏障，障碍
例句：The blood-brain barrier protects the brain from harmful substances.
血脑屏障保护大脑免受有害物质侵害。
trial /traɪəl/ n. a test to assess safety or effectiveness
试验；临床实验
例句：The new vaccine is in Phase 3 clinical trials.
该新疫苗正处于第三阶段临床试验中。
regulate /ˈreɡjəˌleɪt/ v. to control or maintain
调节；控制
例句：The brain regulates hormone levels through complex feedback mechanisms.
大脑通过复杂的反馈机制调节激素水平。
cerebral /ˈsɛrəbrəl/ adj. relating to the brain
大脑的
例句：Cerebral blood flow decreases with age.
随着年龄增长，大脑血流会减少。
improvement /ɪmˈpruːvmənt/ n. a positive change
改善，提升
例句：The treatment led to a significant improvement in memory.
该治疗显著改善了记忆力。
enzyme /ˈɛnzaɪm/ n. a protein that speeds up chemical reactions
酶
例句：Digestive enzymes help break down food.
消化酶帮助分解食物。
clinical /ˈklɪnɪkəl/ adj. related to medical treatment
临床的
例句：The drug has entered clinical trials.
该药物已进入临床试验阶段。
support cell /səˈpɔrt sɛl/ n. a cell that aids neurons but does not transmit signals
支持细胞
例句：Support cells like astrocytes maintain the brain’s homeostasis.
像星形胶质细胞这样的支持细胞维持大脑稳态。
blood-brain barrier /ˈblʌd breɪn ˈbæriər/ n. a selective barrier that prevents certain substances from entering the brain
血脑屏障
例句：Many drugs fail to treat brain disorders because they can’t cross the blood-brain barrier.
许多药物无法治疗脑部疾病，因为它们无法穿越血脑屏障。
functional capacity /ˈfʌŋkʃənl kəˈpæsəti/ n. the ability to perform tasks or activities
功能能力
例句：Improved functional capacity means patients can walk longer distances.
功能能力提高意味着患者能走更远的路。
【astrocyte】/ˈæstrəˌsaɪt/ n. A star-shaped glial cell in the brain and spinal cord. 星形胶质细胞
例句：Astrocytes play an essential role in maintaining the brain’s environment.
星形胶质细胞在维持大脑环境中起着至关重要的作用。
【monoamine oxidase B (MAOB)】/ˌmɒnoʊˈæmiːn ˈɒksɪˌdeɪz biː/ n. An enzyme that breaks down neurotransmitters and is linked to brain disorders. 单胺氧化酶B
例句：MAOB inhibitors are used in the treatment of Parkinson’s disease and other neurological conditions.
MAOB抑制剂用于帕金森病和其他神经系统疾病的治疗。
【inhibitor】/ɪnˈhɪbɪtər/ n. A substance that slows down or prevents a chemical reaction. 抑制剂
例句：This drug acts as an inhibitor of the enzyme responsible for inflammation.
这种药物作为一种炎症相关酶的抑制剂发挥作用。
【extinguish】/ɪkˈstɪŋɡwɪʃ/ v. To put an end to or get rid of something. 消除；扑灭
例句：The therapy helped patients extinguish their fear responses.
这种疗法帮助患者消除了恐惧反应。
【pathological】/ˌpæθəˈlɒdʒɪkl/ adj. Involving or caused by a disease or disorder. 病理的
例句：His pathological anxiety made daily functioning extremely difficult.
他的病态焦虑使日常生活变得极为困难。
【translational】/trænsˈleɪʃənl/ adj. Relating to converting scientific research into practical medical treatments. 转化的
例句：Translational medicine bridges the gap between laboratory discoveries and patient care.
转化医学桥接了实验室发现与临床治疗之间的鸿沟。
【cerebral】/ˈserəbrəl/ adj. Related to the brain. 大脑的
例句：Cerebral blood flow is crucial for healthy brain function.
大脑血流对脑部健康至关重要。
【reversible】/rɪˈvɜːsəbl/ adj. Capable of being changed back to a previous state. 可逆的
例句：The side effects of the drug are reversible after discontinuation.
停药后，药物的副作用是可逆的。
【prefrontal cortex】/ˌpriːˈfrʌntl ˈkɔːteks/ n. The part of the brain involved in decision-making and regulating emotions. 前额叶皮层
例句：The prefrontal cortex is essential in suppressing impulsive behavior.
前额叶皮层在抑制冲动行为方面至关重要。
【blood-brain barrier】/blʌd breɪn ˈbæriər/ n. A selective barrier that prevents certain substances from entering the brain. 血脑屏障
例句：Many drugs cannot cross the blood-brain barrier, limiting their use in brain treatments.
许多药物无法穿过血脑屏障，从而限制了它们在大脑疾病治疗中的应用。
休息一下~~
