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Kognitionsvetenskap (Neurokognition) VT 2011 BRAIN REPAIR YOURSELF By Fred H. Gage SUMMARY By Natalia This article is devoted to the one of the neuroscience’s greatest discoveries: neurogenesis – the birth of new neurons in the brain of adult birds, primates, and humans. For almost 100 years of neuroscience’s history, the idea that the brain doesn’t change in the adult brain dominated. In nineties of the 20th century scientists have discovered that brain actually does change: new cells and new connections are formed throughout lifetime. The author believes that such plasticity offers a possible self-repair mechanism in cases of neurological diseases and injuries or an enhancing mechanism to improve healthy brain’s abilities to think and feel. The birth of a new brain cell is a process, not an event. Multipotent neural stem cells divide periodically in the brain, in two main areas: the ventricles and the hippocampus. In order to develop, either into a neuron or a glia cell, a given stem cell migrates out from the area of influence of the other multipotent stem cells. Researchers have found, that cells that are destined to become neurons, travel from the ventricles to the olfactory bulb. Only half of cells will survive. It takes more than one month for a new neuron to grow up and learn how to function and build active connections with surrounding cells. Whether the young cell becomes neuron or glia (astrocyte, oligodendrocyte) cell depends on where in the brain and when that young cell ends up. Mentioned-above processes are governed by naturally occurring molecules called growth factors. Each step is regulated by different growth factors. For example, the factor named notch as well as bone morphogenetic proteins influence either new cell becomes neuron or glia cell. Nowadays these growth factors are under intensive research. Scientists anticipate that in the future they will learn how to control and regulate neurogenesis and environmental stimuli directly anywhere in the brain, not in a laboratory. By directing neurogenesis, scientists hope to develop therapies that can prompt the brain fix itself in case of disease or injury. The author mentions neurological diseases such as stroke, depression, Alzheimer’s, Parkinson’s, epilepsy, MS, ALS, even glioma and spinal injuries which could be ameliorated by stimulating neurogenesis. After a stroke, through the neurogenesis in the hippocampus, the brain attempts to repair itself by building new neurons, and heal damaged area. Most of the new cells die but some migrate to the damaged area and develop into mature neurons. The amount of the surviving neurons is not sufficient to restore all the damage after a major stroke, but it is believed to be sufficient enough to repair the consequences from a small stroke. Research shows that epidermal growth factor and fibroblast growth factor might enhance repair process. The problem is that those molecules are too large in size to be successfully transported through the blood-brain barrier towards and into the certain brain areas. Depression is believed to be caused by two main factors: genetic predisposition, and chronic stress. It is known, that stress restricts the number of newly generated neurons in the hippocampus. It has been found that available antidepressants, such as Prozac, increase neurogenesis in experimental animals, moreover, it usually takes around one month to elevate mood, using these drugs, the same time, is which required for neurogenesis. That has led to the idea that depression might be partly caused by a decrease in neurogenesis in the hippocampus. Imaging studies show, that chronically depressed patients have shrunken hippocampus, and long term use of antidepressants boost neurogenesis in the rodents’ hippocampus. Increasing neurogenesis might help patients with Alzheimer’s disease. Recent studies show that genetically engineered mice which contained human genes that predispose to Alzheimer’s, exhibited disorders in neurogenesis. There are two kinds of mutant genes: one variation reduces the amount of the neurons in the hippocampus, and the other one reduces the amount of dividing cells, and therefore the amount of the surviving neurons. Author hopes that certain growth factors can fight this trend, and may be useful in fighting the disease. One of the biggest challenge, scientists face now, is to learn more about how the specific growth factors work and influence neurogenesis at each step of the process: the birth, the migration to the right place in the brain, the development and maturation of newborn cells into fully functional neurons, building active connections. In author’s opinion it is also important to learn about where the good balance of the amount of neurogenesis production lays – to find optimum level in stimulating neurogenesis. In case of depression, when the reduced cell division results in cell loss, the goal is to find a drug or develop a therapy, which increases cell proliferation. In case of some forms of epilepsy, scientists speculate that the problem is that newborn cells migrate to wrong locations, remain immature and contribute to miswirings in the brain, which in turn, cause seizures. The solution here would be to learn how to redirect neurons’ migration to the right locations. In case of the brain cancer called glioma, scientists believe that neural stem cells originate the process where glial cells proliferate and form deadly, rapidly growing tumors. Treatment might come from natural substances which regulate the division of those stem cells. Identification of the growth factors which stop neural cells from dying, as well as those, which help immature cells to grow healthy and build active connections with mature functional neurons. Diseases such as Parkinson’s, Huntington’s, ALS, might be the easiest targets to begin with, due to their nature: very specific types of cells, located in the specific brain areas, die and cause motor or cognitive symptoms. In case of MS, ALS, spinal cord injury the right strategy may be to influence neural stem cells to grow into glial cells called oligodenderocytes, which insulate the long axons between neurons, supporting communication between the neurons, preventing the electrical signals from dissipating. However, the author proposes solution which is available already to everyone today. The experience can regulate the rate of stem cell division, the survival rate of the newborn cells in hippocampus. Research shows, that if the adult mice are moved to the more complex and more physically and mentally challenging environments, they will experience a significant increase in neurogenesis. The author also emphasises that the best ways to enhance brain function might not involve drugs but life style and habits changes. Brain, like many other organs, responds positively to exercise, a good diet, and enough sleep. The author also shares his vision of the future, when neurogenesis could be induced in a controlled manner anywhere in the brain, and selective drugs could stimulate necessary steps of neurogenesis to target specific diseases. These pharmacological therapies could be combined with physical therapies which enhance neurogenesis and stimulate particular brain areas to integrate with newly developed cells. The knowledge of positive correlation between neurogenesis, exercise, and increased mental activity might motivate people to enhance their natural ability to repair the brain, and to reduce their risks of neural disorders by changing to healthier lifestyles and choosing mentally and physically challenging activities. He also supposes that future architects and designers could incorporate the knowledge that surrounding environment can affect the wiring in the brain into their work, providing people with homes and workplaces with enriched environments, which stimulate brain function.