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How Do Some Cells Become Brain Cells

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Nerve Cells Do Not Renew Themselves

How do some cells become brain cells and others become skin cells, when the DNA is same?

Your skin cells keep dividing, they die and give birth to new cells all the time, even when youre not injured. After an injury, the skin makes a bunch of new cells and uses them to heal your wound. Yet, nerve cells in your brain, also called neurons, do not renew themselves. They do not divide at all. There are very few exceptions to this rule only two special places in the brain can give birth to new neurons. For the most part though, the brain cannot replenish dead neurons. This is especially worrisome because neurons are very sensitive cells and they die for all sorts of reasons. When you bump your head and suffer a concussion, neurons die. When there is a glitch in the blood supply to the brain, also called a stroke, neurons die. Neurons also die when faced with changes in their own functions, which happens in the so-called neurodegenerative diseases like Parkinsons disease and Alzheimers disease.

Nerve Cells Have Trouble Regrowing Damaged Parts

Looking at the structure of a neuron, you will notice it has a cell body and several arms that it uses to connect and talk with other neurons . The really long arm that sends signals to other neurons is called axon, and axons can be really long. If an axon is damaged along its way to another cell, the damaged part of the axon will die , while the neuron itself may survive with a stump for an arm. The problem is neurons in the central nervous system have a hard time regrowing axons from stumps. Why do skin cells not have this problem? Skin cells are much simpler in structure. And because they can give birth to entirely new cells, they dont face the problem of having to repair parts of their cells.

  • Figure 1
  • Left: the structure of a brain cell. Note the branch-like arms that extend from the cell body . These arms receive incoming signals. The really long arm that extends to the bottom right is called the axon, which sends signals to a receiving cell. The axon is enveloped by a myelin sheath , which helps signals travel faster along the axon to the receiving cell. Right: when an axon gets injured, the end part dies off and leaves an axon stump. Stumps have a hard time to grow back after injury.

So, why do damaged neurons have trouble regrowing axons?

  • Figure 2
  • Growing axons looking for new target cells to connect with have a hard time in an injury environment. This is partly due to star-shaped support cells , which spit out chemicals . These chemicals stop axon growth.

See What Do New Neurons In The Brains Of Adults Actually Do

One pool exists in the brains of adult humans and mice, in an area called the ventricular-subventricular zone . The walls of the two lateral ventricles, cavities filled with cerebrospinal fluid, are lined with stem cells, and along these walls, the cells have a regional identitywhere a stem cell lies on the wall dictates what it differentiates into. This feature has been well-characterized for neuronal subtypes, which are synthesized within discrete domains on the lateral wall. Glial cells are known to be generated at low levels along the septal wall, but the specific subtypes remain unknown because the cells along this wall generally remain inactive.

Nobody expected them to be inside the ventricular system and attached to the wall of the ventricle, and so nobody had ever looked there before. But when you actually look, you can see them really beautifully.

Fiona Doetsch, University of Basel

Fiona Doetsch, a stem cell biologist and neuroscientist at the University of Basel in Switzerland who coauthored the study, has long been fascinated by adult stem cells and what factors regulate this dormancy, or quiescence. People used to think of quiescent cells as the cells just hiding out and not being sensitive to any signals. But actually, the quiescent state is emerging as a very actively maintained state, Doetsch tells The Scientist.

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How Then Does The Brain Repair Itself

Learning about the limitations of neurons compared to skin cells, you may be disappointed that an organ as important as the brain seems to be unprepared for damaging events. The truth is, the central nervous system has an ingenious strategy to repair itself that is entirely different from the strategy used by other organs. The brain will never be the same as before the damage, but it will try to compensate for its losses. Neurons in the brain are able to change their connections with each other. This process is called plasticity, and it helps the brain to adapt to the loss of neurons. Forget for a moment about dying cells, the responsibility for plasticity lies entirely with the surviving cells. How does this work?

  • Figure 3
  • In response to an injury, a brain cell can adapt by growing new arms and also by increasing or decreasing the strength of existing connections .

Transcription Factors Guide The Cells To Become A Specific Type

After You Die, Some Cells in Your Brain Become More Active

Co-first author Matheus B. Victor, a graduate student in neuroscience, says they believe the small RNA molecules are doing the heavy lifting, and:

They are priming the skin cells to become neurons. The transcription factors we add then guide the skin cells to become a specific subtype, in this case medium spiny neurons. We think we could produce different types of neurons by switching out different transcription factors.

The team also showed that when the skin cells are exposed to the transcription factors alone, without the small RNA molecules, the skin cells do not convert successfully.

The team also carried out extensive tests to show the new brain cells had the hallmarks of native medium spiny neurons. They expressed the right genes for their specific type and did not express genes for other types of neurons.

And, when transplanted into the brains of mice, the converted cells looked like native medium spiny neurons and behaved like them.

The team is now using skin cells from patients with Huntingtons disease and converting them into medium spiny neurons using their new approach. They also plan to inject the cells into mice with the disease.

The study was funded by various bodies, including the National Institutes of Health .

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How To Grow New Brain Cells And Make Yourself Smarter

Growing new brain cellsor neurogenesisis possible for adults.

For a long time the established dogma was that the adult brain couldnt generate any new brain cells. That is, it was believed that you were born with a certain amount of brain cells, and that was it. And since you naturally lose brain cells as you age, after age 25 it was all downhill for your brain function.

The good news is that scientists have now discovered that you can grow new brain cells throughout your entire life. The process is called neurogenesis. Specifically, new brain cellswhich are called neuronsgrow in the hippocampus. This is the region of the brain that is responsible for learning information, storing long-term memories, and regulating emotions. This has many different positive implications. Here are some of the most important ways in which taking action to encourage neurogenesis can help you:

  • As Dr. Amar Sahaya neuroscientist with Harvard-affiliated Massachusetts General Hospitalexplains, developing new brain cells can help enhance cognitive functions. New neurons enhance your ability to learn.
  • Growing new neurons can help you stave off Alzheimers.
  • Neurogenesis will help you to keep your memory sharp.
  • The growth of new brain cells can both treat and prevent depression, as well as help to reduce anxiety.

In order to make the most of your brain you need to do the following:

  • Take Care of Your Brain Cells
  • Grow New Brain Cells
  • Keep the New Neurons From Dying

Finding The Right Sequence

Contrary to the way some researchers screen for new drugs or biologically relevant molecules testing thousands of different molecules in different combinations with machines, for example the Studer team lit upon this particular recipe through a more artisanal approach.

A theme of our lab is that we dont use brute-force approaches to develop protocols, says Yuchen Qi, a postdoctoral fellow in the Studer lab and the papers first author. Instead, we focus on the real biological cues that we know to be involved in the development of these neurons.

Still, it was tricky to come up with a winning formula. Much like baking a soufflé, the order in which you combine the ingredients, and how much you use of each, can make the difference between a successful pastry and a total flop.

Switching metaphors, Dr. Studer likens the process to playing a piece of music. There are only eight notes in an octave, but you can play those notes in many different ways, he says. Its almost like each cell type has its own melody. Once you figure it out, you can get better and better at playing it.

The music metaphor is appropriate given what the team did next: They implanted the human neurons in developing mouse brains and followed their growth using a powerful new visualization technique called iDISCO . With iDISCO, the team could create movies that show what happens to the human neurons over the course of six months as they boogied their way across the mouse brain.

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Benign And Malignant Growth

Cells become abnormal if their DNA which carries the instructions they need becomes damaged. Then the cells that come from them will be different from healthy cells. They look different, and they may also have different properties. If these kinds of abnormal cells grow in body tissue such as skin, for example it is referred to as dyplasia. As long as there are very few abnormal cells and they’re kept under control by our immune system, they won’t harm us. Sometimes these kinds of cells will also go away on their own. It is only when they keep on changing and start to divide uncontrollably, forming lumps or growths, that one of the more than 200 diseases called cancer develops. Growths like this are called tumors.

The main differences between malignant and benign tumors are that malignant ones can

  • spread into the surrounding tissue,
  • destroy the surrounding tissue, and
  • cause other tumors to develop.

Malignant tumors can be life-threatening. But there are also some kinds of cancer that develop so slowly in older people that they don’t lead to any problems in their lifetime. Benign tumors usually don’t cause much damage and aren’t normally life-threatening. But there’s no guarantee: Benign growths can become dangerous if they grow a lot, or they might become malignant after a certain amount of time.

Carcinoma in situ

Invasive cancer

The Development Of Cancer

How Cells Become Specialized

One of the fundamental features of is clonality, the development of tumors from single cells that begin to proliferate abnormally. The single-cell origin of many tumors has been demonstrated by analysis of X chromosome inactivation . As discussed in Chapter 8, one member of the X chromosome pair is inactivated by being converted to in female cells. X inactivation occurs randomly during embryonic development, so one X chromosome is inactivated in some cells, while the other X chromosome is inactivated in other cells. Thus, if a female is heterozygous for an X chromosome , different alleles will be expressed in different cells. Normal tissues are composed of mixtures of cells with different inactive X , so expression of both alleles is detected in normal tissues of heterozygous females. In contrast, tumor tissues generally express only one of a heterozygous X chromosome gene. The implication is that all of the cells constituting such a tumor were derived from a single cell of origin, in which the pattern of X inactivation was fixed before the tumor began to develop.

Tumor clonality. Normal tissue is a mosaic of cells in which different X chromosomes have been inactivated. Tumors develop from a single initially altered cell, so each tumor cell displays the same pattern of X inactivation

Increased rate of colon cancer with age. Annual death rates from colon cancer in the United States.

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Show/hide Words To Know

Differentiation: when a cell chooses a particular genetically determined path that causes it to perform only a few specialized tasks… more

DNA : molecular instructions that guide how all living things develop and function…more

Egg: a female gamete, which keeps all the parts of a cell after fusing with a sperm.

Gamete: specialized cells found in your reproductive organs that have half the amount of DNA of somatic cells. These cells combine to make a fertilized egg… more

Gene: a region of DNA that instructs the cell on how to build protein. As a human, you usually get a set of instructions from your mom and another set from your dad… more

Nucleus: where DNA stays in the cell, plural is nuclei.

Organism: a living thing that can be small like bacteria or large like an elephant.

Somatic cells: the cells in your body, except for gametes. Soma is Latin for body.

Sperm: a male gamete, which which fuses with the egg during fertilization… more

Why Dont Neurons Undergo Mitosis

Cells dont start out knowing what their function is. They are like babies with an unknown future. These early cells replicating during zygote formation are called embryonic stem cells. They can form any cell in the body and have an almost limitless capacity to divide. But as they replicate more times, the cells begin to pick their function. This process is called differentiation. As cells continue to specialize in a certain set of functions, they lose the capacity to divide.

Neurons are extremely specialized cells. Due to their unique power and function within the body, the connections and pathways that are established between nervous centers are interconnected and valuable. Most of the cellular resources in a neuron are devoted to communicating and carrying electrochemical messages to other neurons.

Neuron network

Similar to cardiac muscle cells dedicating all their energy to pumping your blood, neurons dont have time or resources to copy themselves and reproduce.

Furthermore, since these cells are so highly specialized and the intricate network of communication is so complicated, the addition of new nerve cells could disrupt those pathways, affecting the normal function of the body, its muscles, and ability to communicate effectively.

For this reason, protecting your brain and spinal cord is of the utmost importance. Any potential damage or risk to your nervous system should be taken very seriously, as those cells wont simply replicate overnight.

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Converted Cells Showed Properties Of Native Cells

Senior author Dr. Andrew S. Yoo, assistant professor of developmental biology at WUSTL, says not only did the new cells survive in the mouse brain, but they also showed properties similar to native cells:

These cells are known to extend projections into certain brain regions. And we found the human transplanted cells also connected to these distant targets in the mouse brain. Thats a landmark point about this paper.

Because they used adult human skin cells in the study and not mouse cells or human cells at an earlier stage of development the team believes the work shows the potential for using patients own cells in regenerative medicine. This is important because therapies can use readily available cells and also avoid the problem of immune rejection.

For their study, Dr. Yoo and colleagues cultured the skin cells in an environment that mimics that of brain cells. In previous work, they had already discovered that exposing skin cells to two small RNA molecules called miR-9 and miR-124 can turn them into different types of brain cell.

Although they are still trying to work out exactly what happens, the team believes the two small RNA molecules open up the tightly packed DNA inside cells that holds instructions for making brain cells, allowing the genes particular to their development and function to be switched on.

The Brain Can Produce New Cells

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But neuroscientists led by QBI’s founding director, Professor Perry Bartlett, discovered stem cells in the hippocampus of the adult brain in the 1990s. Because stem cells can divide, and differentiate into many types of cells, the game-changing discovery suggested that neurogenesis could hold the key to treating conditions such as Alzheimers disease.

Neurogenesis is now accepted to be a process that occurs normally in the healthy adult brain, particularly in the hippocampus, which is important for a learning and spatial memory. Damage to the hippocampus can lead to difficulties with navigation, as Dr Lavinia Codd found when, at age 31, she had a stroke that damaged her right hippocampus.

Earlier this year, QBI researchers made the world-first discovery that new adult brain cells are also produced in the amygdala, a region of the brain important for processing fear and emotional memories.

The amygdala, an ancient part of the brain, is important for attaching emotional significance to memories, and also plays a key role in fear learning, which causes us to learn that an experience or an object is frightening.

Fear learning leads to the classic flight-or-fight response increased heart rate, dry mouth, sweaty palms but the amygdala also plays a role in producing feelings of dread and despair, in the case of phobias or PTSD, for example, says lead researcher Dr Dhanisha Jhaveri.

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How Does One Cell Become A Brain Cell And Another A Skin Cell

This is called cell differentiation and it is driven by chemicals/chemical gradients in the blastula development stage of the embryo . These chemicals have the effect of causing the cells in different areas of the ball to start doing different things from other areas. The DNA in all the cells is the same but different bits of DNA are used for making proteins/enzymes as the cells differentiate.

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Because it is believed that cells have the ability to turn off some genes and only use certain ones that are needed for the specific job that the cell is doing.

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While the DNA in one’s cells may be the same, not all of the genes are active at the same time. Some genes code for proteins that regulate the expression of other genes, for example. In addition, internal conditions in the cells during development of the embryo may affect the order in which certain genes are expressed as well. This differential gene expression results in the diversity of tissues we see.

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The DNA in every cell in an organism, such as a person, is indeed the same. It is like an encyclopedia. But in every cell only some of the pages of the encyclopedia are open and being read.

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