Sandra Reichstetter, PhD – Brain Blogger Health and Science Blog Covering Brain Topics Wed, 30 May 2018 15:00:03 +0000 en-US hourly 1 What Stem Cells Need to Survive in the Brain Sun, 06 Feb 2011 17:17:38 +0000 Stem cells have been a hot and also controversial topic in research and in the media for the last few years, as they might be used in the future to repair injured tissue in such diverse disease like heart attacks, strokes, Alzheimer’s disease, Parkinson’s disease and many more. But, there are also unsolved ethical issues about their procurement. There is a lot of confusion about what is meant by the expression “stem cells” in the media.

In principal there are three kinds of stem cells:

  • Embryonic stem cells. These cells are present in an embryo. They have the ability to develop into all of the different tissues types within the embryo. To use these cells in research (or in the future for therapies) embryos have to be destroyed which makes the use of these cells highly controversial.
  • Adult stem cells. These are cells isolated from adult tissues that retain the ability to develop into a limited number of different kinds of cells. These stem cells are the cells that repair injuries in adult organs.
  • Induced stem cells. In theory, cells from any tissue can be reprogrammed to go back to a state in which they behave like embryonic stem cells. While this has been understood in principal, and there are many examples of them in research, the reprogramming involves the use of genes that can also cause cancer, so that the use of induced stem cells still is hampered by safety issues.

Many adult organs such as the liver contain adult stem cells which give these organs impressive regenerative capacity. Most areas of the adult brain, however, do not contain any stem cells, which is most likely the reason, why brain injuries are so hard to repair. In a recent publication, researchers from the University of California, Berkeley, showed that stem cells in the brain of juvenile fruit flies need two different signals to persist into adult life: a signal from insulin which acts as a growth factor and the disruption of signals that lead to programmed cell death (apoptosis). If these findings hold true for the survival of stem cells in mammalian brains, they could be used in the future to re-introduce stem cells into a injured or diseased area of an adult brain and keep them alive long enough for tissue repair to happen. Remaining stem cells could then be starved off the insulin to remove them and thus reduce the risk that they will develop into cancer cells later on. However, since the brain cannot act as a source for adult brain stem cells, these stem cells would need to be induced or embryonic stem cells. Even if ethical concerns are not considered, much research is still necessary before these stem cells are safe enough to be used in humans.


Siegrist SE, Haque NS, Chen CH, Hay BA, & Hariharan IK (2010). Inactivation of both Foxo and reaper promotes long-term adult neurogenesis in Drosophila. Current biology : CB, 20 (7), 643-8 PMID: 20346676

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Genetics Clues May Lead New Treatment for Parkinson’s Disease Thu, 27 Jan 2011 12:00:50 +0000 Parkinson’s disease (PD) is a neurodegenerative disorder in which mainly nerve cells in the substantia nigra of the brain die. This region is a central area of the brain that is involved in the control of movements. The cells in this area produce a neurotransmitter (messenger molecule between nerve cells) that is called dopamine and why these cells specifically succumb in PD is not completely clear. However, recent research produced hints that the dopamine-producing cells in the substantia nigra are particularly sensitive to disruptions in the energy production of the cells.

Brain cells in general are very dependent on well-working energy production machinery, as their energy requirements are among the highest in the body: the brain uses about 20% of the body’s energy, while it has only about 2% of the body’s weight which might make the brain more sensitive than other organs to disruptions in this system. It has been known since a while that the cell’s power plants called mitochondria often show defects in PD patients.

A study that was recently published in the journal Science Translational Medicine now shows even more conclusive evidence that energy production is impaired in this disorder. The researchers analyzed the expression of genes in tissue samples collected from diseased PD patients and found 10 different sets of genes showing decreased expression in the patients that was not found in healthy controls. Interestingly, all ten sets of genes pointed to one common activator as a master-regulator of cellular energy production, a protein called peroxisome proliferator–activated receptor g coactivator-1a (PGC-1a). It is known since longer that activation of PGC-1a can treat PD in mouse models of the disease. This decrease in action of the PGC-1a gene that ultimately leads to the demise of the dopamine producing neurons in the substantia nigra probably starts years before the appearance of the first symptoms of the disease.

Still, these findings open new avenues in treating early disease and preventing further damage to the nerve cells and progression of the disorder. Medications that can activate PGC-1a are already in use for other diseases like for example diabetes. Unfortunately it is not possible to simply give these medications to PD patients, as they can only work if they can get to the brain. A biological barrier that protects our brains from toxic substances that are in the blood stream like alcohol, drugs, and toxic degradation products of the metabolism called the blood-brain-barrier also keeps these medications out of the brain. Nevertheless, the knowledge what kind of medications can activate PGC-1a can lead to a faster development of drugs that can do the same and reach the necessary areas in the brain to work for PD patients.


Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, Eklund AC, Zhang-James Y, Kim PD, Hauser MA, Grünblatt E, Moran LB, Mandel SA, Riederer P, Miller RM, Federoff HJ, Wüllner U, Papapetropoulos S, Youdim MB, Cantuti-Castelvetri I, Young AB, Vance JM, Davis RL, Hedreen JC, Adler CH, Beach TG, Graeber MB, Middleton FA, Rochet JC, Scherzer CR, & Global PD Gene Expression (GPEX) Consortium (2010). PGC-1?, a potential therapeutic target for early intervention in Parkinson’s disease. Science translational medicine, 2 (52) PMID: 20926834

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How Prozac works Wed, 20 Oct 2010 03:52:45 +0000 The tightly regulated balance between secretion and removal of neurotransmitters is not functioning properly in certain mental conditions like bipolar disorder, obsessive-compulsive disorder, anxiety, and depression. Neurotransmitters are signaling molecules used to transmit messages between neurons (nerve cells) in the brain. Serotonin is one of the neurotransmitters affected in depression and similar disorders. The most common class of drugs for the treatment of these conditions is called selective serotonin reuptake inhibitors (SSRI). The well-known Fluoxetine (Prozac) is a member of this class.

SSRIs work on the serotonin balance by inhibiting a transporter called SERT that selectively pumps serotonin back into the neurons. The action of the SERT molecule shortens the time that serotonin has to deliver its signal, inhibiting SERT therefore increases serotonin function. How exactly SSRIs inhibits SERT has not been clear until now, even though researchers knew that the mechanism cannot just be a simple binding to SERT and thus preventing SERT from binding to serotonin. If this were the case, the action of the drugs should kick in fully at latest a few days after the patient started taking them. One of the most perplexing properties about SSRIs, however, is that it can take weeks to months before they are fully active. Researchers therefore believed since a long time that SSRIs inhibit the SERT in a different way. Still, the exact mechanism was not known until now.

In a recent publication in Science, a team of researchers showed a possible mechanism of action for Fluoxetine. According to these scientists, it works through a completely new inhibitory pathway, which can also explain the lengthy and for patients often very frustrating waiting time before SSRIs work clinically. They found that in mice chronically fed with Fluoxetine, the expression of the gene that encodes the blueprint of SERT is reduced, which means less SERT is available to remove serotonin from the synapse. This is a surprising finding in itself, still, the mechanism how Fluoxetine down-regulates the SERT expression is even more surprising.

Gene expression works in two steps: DNA, the genetic material is copied into a working draft in the form of RNA, called messenger or mRNA. Proteins, which are the building blocks of our cells are then read from this RNA-copy of the gene. The mRNA is highly unstable, and its degradation ensures that no more new protein than necessary is produced. Until recently, scientists believed that gene expression is regulated by proteins that bind to the DNA telling the gene-expression-machinery directly where and how often to read the blueprint to make a new protein. Newer research shows that this is not the only way to regulate gene expression, and a very important component of gene regulation takes place a later point, when the mRNA  is translated into a new protein. Non-protein encoding RNA molecules called micro-RNAs can also regulate how often a gene is read or they regulate how long the mRNA molecule sticks around before it gets degraded. This determines how much protein is produced from this mRNA molecule.

The researchers now showed that a newly found micro-RNA called micro-RNA 16 decreases SERT expression. In the Fluoxetine-fed mice, Fluoxetine increased the expression of this micro RNA. As a result, lower levels of SERT were produced, leading to prolonged serotonin action. This mechanism only affects the levels at which new SERT molecules are produced. SERT already present in the neuron is unaffected, so that the effect of the drug will only be noticeable after several weeks of taking it, when old worn-out SERT molecules are replaced at a lower rate than what they would be without Fluoxetine.


Baudry A, Mouillet-Richard S, Schneider B, Launay JM, & Kellermann O (2010). miR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants. Science (New York, N.Y.), 329 (5998), 1537-41 PMID: 20847275

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Instant Antidepressants on the Horizon Sat, 16 Oct 2010 12:00:51 +0000 Depression and similar mental disorders like bi-polar disorder, anxiety, and obsessive–compulsive disorder are associated with imbalances in neurotransmitters in the brain. Neurotransmitters are signaling molecules exchanged between neurons (nerve cells) for communication purposes. One of these neurotransmitters is serotonin, and drugs that increase serotonin levels in the brain are the most widely used treatments for depression and similar conditions. Nevertheless, these drugs are not unproblematic as many patients get frustrated as it can take several weeks after taking them, before the drugs become effective, in some patients, the drugs work don’t work at all, and in others, the side effects of these drugs can be a huge problem.

The molecules in the brain to which serotonin binds to deliver its signal, are called serotonin receptors. There are seven families of serotonin receptors known and each family has a different function; some of them even have opposite effects. Conventional anti-depressants increase serotonin levels in all parts of the brain and make no difference which serotonin receptors are present in the areas they affect. A better understanding which serotonin receptor is responsible for anti-depressive and anxiety-reducing effects of serotonin could lead to the development of medications that specifically target these receptors and therefore reduce side effects and increase efficacy of the treatment compared to the current “shot-gun” approach.

In a recent publication in the journal Proceedings of the National Academy of Science (PNAS), scientists have come one step closer to this ideal. They showed that increasing the activity of the serotonin receptor 5HT1A leads to a decrease of behavior in mice that is linked to depression and anxiety. 5HT1A is a member of the 5HT1-family of serotonin receptors that is located on the cell surface of certain neurons (nerve cells) that receive serotonin signals. The signal is transmitted into the neuron by another molecule, called a G-protein which is hooked to the 5HT1A-receptor on the inside of the cell membrane. The activity of this G-protein can be turned down by another protein called a regulator of G-protein signaling (RGS).

In the publication, the researchers reported about mice in which the RGS cannot turn down the G-protein’s activity due to a mutation in the G-protein. These mice showed behaviors without being given any drugs that are usually seen when antidepressants are given to mice. These mice also reacted much stronger when they were given serotonin-increasing antidepressants when compared to control mice that did not have the mutation. These finding show that the RGS protein plays an important part in decreasing the anti-depressant effect of the 5HT1A receptor. A future medication that selectively inhibits the action of the RGS protein might be a more effective treatment for depression and related conditions, with the risk of fewer side effects compared to the current unspecific serotonin-enhancing drugs.


Talbot JN, Jutkiewicz EM, Graves SM, Clemans CF, Nicol MR, Mortensen RM, Huang X, Neubig RR, & Traynor JR (2010). RGS inhibition at G(alpha)i2 selectively potentiates 5-HT1A-mediated antidepressant effects. Proceedings of the National Academy of Sciences of the United States of America, 107 (24), 11086-91 PMID: 20534514

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