刺激神经发生的新策略可能导致药物改善认知和情绪

纽约 - 研究员在哥伦比亚大学医学中心已发展到刺激神经元生产的成年小鼠大脑的新途径，证明了成年期间，在大脑的海马体神经元获得一定改善认知功能。近年来，科学家们一直在探索是否在成人大脑刺激神经发生（新神经元的形成）对认知或情绪有益的影响。到现在为止，研究依赖于干预措施，如运动和丰富的环境中，会影响许多其他过程在大脑中除了增加成年海马神经发生。这项研究由勒内母鸡，博士，神经科学和药理学教授，神经科学和精神病学在哥伦比亚大学和院系纽约州立精神病研究所牵头，出现在自然杂志的预先在线公开。阿马尔萨海，博士，博士后，是这项研究的主要作者。促进在海马神经元的数量后，参与记忆和情绪的大脑区域，研究人员在两者的学习和情绪相关的任务测试小鼠寻找行为的改变。研究人员发现，学习涉及称为模式的分离过程，这是类似的地方，事件和经验来区分能力的任务具体影响。“这个过程是学习，因为它使我们能够知道的东西是否熟悉或新颖的关键，”母鸡博士说。“如果是熟悉的，你移动到下一个信息位;如果它是新的，你要能够认识到它是新的，赋予它意义。 These mice, with just more adult-born neurons, and no other changes in the brain, basically learn better in tasks where they have to discriminate between similar contexts.” Earlier strategies for manipulating neurogenesis, according to the investigators, were broader and less specific. “In addition to stimulating neurogenesis, these earlier methods exerted many other effects on the brain. As a result, you never knew with these older manipulations what’s due to neurogenesis, or what’s due to the other effects that these manipulations cause, and, indeed, what we find is that when you stimulate just adult neurogenesis, you actually get a subtle effect. Unlike broader manipulations, it does not affect all forms of learning, it’s very specific to tasks that require pattern separation,” said Dr. Hen. Pattern separation is not only important for learning; it may also be important for anxiety disorders, including post traumatic stress disorder (PTSD) and panic disorder. People with PTSD, say the researchers, have a more generalized fear response, so that when they are placed in a situation that reminds them of even one aspect of their trauma, they frequently have a full fear response. “I think a good example of this is someone who has developed PTSD as a result of 9/11. For them, the simple sight of an airplane or high tower may be enough to reawaken the initial traumatic episode and bring back the full aversive memory. Sometimes these generalizations become so pervasive that people basically don’t want to leave their home anymore because everything reminds them of the original event,” said Dr. Hen. The normal adaptive response, say the authors of the study, is to separate similar events or experiences. “Even though I may remember 9/11, when I see an airplane over NYC, I am able to recognize that it’s a different situation and process it accordingly, while someone in the same situation with PTSD may re-experience the traumatic memory of 9/11 and have a panic attack. So this may be one reason why stimulating neurogenesis to improve pattern separation may contribute to treatment of some of these anxiety disorders,” said Dr. Hen. Enhancing pattern separation, by either the method the Columbia researchers used, or other strategies, may also be useful in treating some of the learning deficits seen in people with normal or pathological aging, such as Alzheimer’s disease. In fact, there is already evidence that pattern separation declines during normal aging. “This paper, as a consequence, may stimulate a whole area of research in humans to try to determine who in the population may have a pattern separation deficit, and whether it is restricted to the emotional domain, or is present even while performing tasks devoid of emotional salience. Once these studies are done in humans, it may be possible to treat these people with specifically targeted drugs or more personalized therapies,” said Dr. Hen. The researchers say that the genetic strategy used to stimulate neurogenesis in their experiments can be mimicked pharmacologically, potentially leading to the development of new drugs to reverse pattern separation deficits. One such class of drugs the investigators are currently testing – BAX inhibitors – works by blocking cell death. “These drugs are basically doing the same thing that we did with our genetic manipulation–namely, increasing the survival of the young neurons which normally undergo a process of cell death that eliminates at least half of these neurons. Now instead of dying, the neurons will go on to survive,” said Dr. Sahay. Some BAX inhibitors have been developed for stroke research, where the goal has also been to prevent neurons from dying. The Columbia researchers plan to begin testing the BAX inhibitors in mice shortly. And if they produce cognitive benefits, the testing will be extended to clinical trials to determine if there’s also a beneficial effect in humans. “I think we’re getting closer to harnessing neurogenesis to improve cognition and mood in humans. This research may also help explain a bit of a mystery in the field, which we still don’t understand, regarding how the hippocampus can be involved with both cognition – which is its classic function – and in mood and anxiety-related functions. Perhaps the fact that pattern separation affects both the cognitive and mood domains is the beginning of an answer to that paradox,” said Dr. Hen. Authors of the Nature study are Amar Sahay, Kimberly N. Scobie, Alexis S. Hill, Colin M. O'Carroll, Mazen A. Kheirbek, Nesha S. Burghardt , André A. Fenton, Alex Dranovsky and René Hen. This study was supported in part by: the National Institute of Mental Health (NIMH); National Alliance for Research on Schizophrenia and Depression (NARSAD); New York Stem Cell Initiative (NYSTEM); Ruth L. Kirschstein National Research Service Awards (NRSA); and the Sackler Institute of Columbia University. The authors of this study have reported the following financial interests: Dr. Hen is a consultant to Brain Cells, Inc., and Astra Zeneca. -####- Columbia Psychiatry is ranked among the best departments and psychiatric research facilities in the Nation and has contributed greatly to the understanding of and current treatment for psychiatric disorders. Located at the New York State Psychiatric Institute on the NewYork-Presbyterian Hospital/Columbia University Medical Center campus in the Washington Heights community of Upper Manhattan, the department enjoys a rich and productive collaborative relationship with physicians in various disciplines at Columbia University's College of Physicians and Surgeons. Columbia Psychiatry is home to distinguished clinicians and researchers noted for their clinical and research advances in the diagnosis and treatment of depression, suicide, schizophrenia, bipolar and anxiety disorders, and childhood psychiatric disorders.

哥伦比亚大学医疗中心在医疗和健康科学教育和患者护理中提供了基础，临床前和临床研究的国际领导。医疗中心培训未来领导人，包括许多医生，科学家，公共卫生专业人士，牙医和护士的专门工作，在医师和外科医生，公共卫生学院，牙科医学院，护理学院，艺术与科学研究生院的生物医学部门，以及联合研究中心和机构。哥伦比亚的医生和外科医生成立于1767年，是该国第一个授予M.D.学位的机构，是该国最具选择的医学院之一。哥伦比亚大学医疗中心是纽约市最大的医学研究企业的所在地，也是美国最大的家园。