是什么赋予了人类大脑的独特性?在多种解释中还尚缺髓磷脂(myelin)部分。
传统观点认为髓磷脂(Myelin)只是围绕在神经细胞轴突外面的一层脂质,如同包绕电线的绝缘外皮,起保护和绝缘的作用。最近加州大学洛杉矶分校(UCLA)神经学教授George Bartzokis博士发现髓磷脂问题涉及面及广,从精神分裂症到阿尔茨海莫等一系列疾病都与其有关。研究结果刊登于《Biological Psychiatry》杂志。
Bartzokis博士说髓磷脂“进化历史不长,脊椎动物有而无脊椎动物无。人类相比于其它动物有更多的髓磷脂。”
Bartzokis研究报道过的类胆碱药(Cholinergic)的治疗结果。类胆碱药能够改善阿尔茨海莫氏症等疾病患者的神经突触信号传递。他发现一些临床和理论数据提示,这种治疗有可能更改甚至推迟这些疾病。
以髓磷脂为中心研究这种效果,Bartzokis认为Cholinergic治疗也会产生非突触性效果(nonsynaptic effects),可能是通过增强髓鞘形成和髓磷脂修复——髓磷脂质量越高,神经信号传递以及“网络”(Internet)功能越好。特别是,这种Cholinergic治疗能够增强少突细胞(oligodendrocytes)的活性。少突细胞是大脑中的一种神经胶质细胞,在大脑发育过程中产生髓磷脂,并随着年龄增长对髓磷脂起维持、修复作用。
尽管弄清Cholinergic的非突触性效果在大脑发育中的作用还需要做更多的工作,但Bartzokis推测在大脑内部进行在体成像,研究髓磷脂的损毁和生成,能够轻松解决上述难题。这些使直接在人体中检测人脑髓磷脂中心模型的实际效用成为可能。
“尽管这些某种程度上说是良性干扰,”Bartzokis说:“对大脑宝贵的少突细胞数量的影响能够能够抑制脑部疾病。它们值得仔细研究。”
英文原文:
Myelin to Blame for Many Neuropsychiatric Disorders
What makes the human brain unique? Of the many explanations that can be offered, one that doesn't come readily to mind is — myelin.
Conventional wisdom holds that myelin, the sheet of fat that coats a neuron's axon — a long fiber that conducts the neuron's electrical impulses — is akin to the wrapping around an electrical wire, protecting and fostering efficient signaling. But the research of UCLA neurology professor George Bartzokis, M.D., has already shown that myelin problems are implicated in diseases that afflict both young and old — from schizophrenia to Alzheimer's.
Now, in a report published in the journal Biological Psychiatry and available online, Bartzokis argues that the miles of myelin coating in our brain are the key "evolutionary change that defines our uniqueness as a species" and, further, may also be the cause of "our unique vulnerability to highly prevalent neuropsychiatric disorders." The paper argues that viewing the brain as a myelin-dependent "Internet" may be key to developing new and novel treatments against disease and aid in assessing the efficacy of currently available treatments, including the use of nicotine (delivered by a patch, not smoking), which may enhance the growth and maintenance of myelin.
Myelin, argues Bartzokis, who directs the UCLA Memory Disorders and Alzheimer's Disease Clinic, is "a recent invention of evolution. Vertebrates have it; invertebrates don't. And humans have more than any other species."
Bartzokis studied the reported effects of cholinergic treatments, using drugs that are known to improve a neuron's synaptic signaling in people who suffer diseases like Alzheimer's. Furthermore, he notes, some clinical and epidemiological data suggest that such treatments may modify or even delay these diseases.
Looking at such effects from a myelin-centric point of view, Bartzokis argues that cholinergic treatments may have nonsynaptic effects as well, perhaps by enhancing myelination and myelin repair — and the better the myelin, the more efficient the neuron signaling and our "Internet's" function. Specifically, such cholinergic treatments may enhance oligodendrocytes, a type of glia cell in the brain that produces myelin during the brain 's development and constantly maintains and repairs it as we age.
While more work needs to be done to fully understand the role of nonsynaptic cholinergic effects on brain development, said Bartzokis, his hypotheses can easily be tested through in vivo imaging of the brain to study the breakdown and growth of myelin. That will make it possible to directly test in humans the practical utility of the myelin-centered model of the human brain.
Ultimately, it could foster the development of novel treatments, as well as aid in assessing the efficacy of currently available treatments. These include the use of cholinergic treatments that include acetylcholinesterase inhibitors (used to treat Alzheimer's) and nicotine patches.
"Through these rather benign interventions," Bartzokis said, "such effects on the brain's vulnerable oligodendrocyte populations may offer exciting opportunities for the prevention of both developmental and degenerative brain disorders. They deserve much closer scrutiny."
Bartzokis work was supported in part by a National Institute of Mental Health grant, a National Institute on Aging Alzheimer's Disease Center Grant, Research and Psychiatry Services of the Department of Veterans Affairs and the Sidell-Kagan Foundation.