the nerve blog » stem cells

Don’t Panic! – Mice Aren’t Actually the Smartest

Reena Clements — Wed, 03 Apr 2013 01:33:31 +0000

“Man had always assumed that he was more intelligent than dolphins because he had achieved so much — the wheel, New York, wars and so on — whilst all the dolphins had ever done was muck about in the water having a good time. But conversely, the dolphins had always believed that they were far more intelligent than man — for precisely the same reasons….In fact there was only one species on the planet more intelligent than dolphins, and they spent a lot of their time in behavioural research laboratories running round inside wheels and conducting frighteningly elegant and subtle experiments on man. The fact that once again man completely misinterpreted this relationship was entirely according to these creatures’ plans.” – Douglas Adams, The Hitchhiker’s Guide to the Galaxy

As tempting as it may be to believe the science fiction version of the intelligence rankings, real-life science has spoken and suggests (much to my displeasure) that humans may actually be the highest on the intelligence scale.

Glia are non-neuronal cells found in the brain mainly described as performing “housekeeping” functions, for example, providing structural support to neurons, and providing them with nutrients. Astrocytes are a specific type of glia, and as one might hypothesize, they are bigger in humans than in mice. Was this just a consequence of humans having more complex brains, or do these astrocytes have different functions in humans beyond the basic housekeeping functions? To test this, scientists grafted human astrocyte progenitor cells into developing mouse brains to create chimeric mice.

Human astrocyte (green) and mouse astrocyte (red)

The human astrocytes that matured successfully matured as human cells; characteristics such as their size were unaffected by being in a mouse environment. But they did not remain completely foreign – they successfully formed electrical connections with the mouse cells. Their differing cellular properties were thus propagated into the mouse neural networks. Of particular interest is the hippocampus, the brain region important for learning and memory. Chimeric hippocampal slices had a higher level of baseline excitatory activity, and long-term potentiation (LTP), or synapse strengthening, was much greater. At the molecular level, this can be explained because the human cells express higher levels of a protein that promotes an increased number of glutamate receptors at the synapse.

There were also clear differences in the behavior of chimeric mice. Experiments were performed to test learning and memory abilities to corroborate the cellular results observed in the hippocampus. A classic fear conditioning experiment involves pairing a tone with a foot shock; mice learn to associate the two and exhibit freezing behavior after hearing a tone. Chimeras learned the association after only one tone/shock pairing. The learning persisted for several days, during which time control animals did not learn the initial association. The experiment was repeated as context fear conditioning, meaning that the mice were placed in different chambers that had varying floors and odors. Chimeric mice were able to differentiate between chambers significantly better than their control counterparts. In other learning and memory tasks, these mice learned their way through mazes faster and were better at familiar object recognition in novel contexts.

The results of this study show that glial cells have much more function beyond their basic housekeeping properties. A single cell graft manipulation was enough to significantly improve mouse performance on learning and memory tasks. Complexity of these cells has evolved with the brain, and this provides important new insight on how exactly this complexity has come to be. Future experiments could involve grafting chimpanzee or macaque glia, any differences observed could be key in outlining how our processing abilities evolved from our monkey fathers (I additionally support research with dolphin glia grafts, keeping on the theme of the three most intelligent species). Unfortunately, without the higher processing abilities made possible by human cells, mice likely cannot achieve the tasks and level of status they exhibit in the science fiction. It seems as though man has indeed correctly interpreted his relationship with the mouse.

So long, and thanks for all the fish.

-Reena Clements

References:

Human Brain Cells Boost Mouse Memory – ScienceNOW

Forebrain Engraftment by Human Glial Progenitor Cells Enhances Synaptic Plasticity and Learning in Adult Mice – Cell Stem Cell

Are you flushing away brain cells? How urine cells can give rise to neurons

Matthew Larkey — Thu, 07 Mar 2013 18:30:14 +0000

Uh-oh, urine trouble! Well, now that that’s out of my system (ahem), how would you feel if you learned that you’ve been flushing away potential brain cells? I’m not talking about the copious amount of hours you’ve logged online or kicked back in front of the television just this past month. On a daily basis, you’re expelling 1-2 liters of a possible source of neurons in a way you’ve never expected – through urinating.

Back in 2009, stem-cell biologist Duanqing Pei demonstrated that kidney epithelial cells, a common component of urine, could be converted into induced pluripotent stem (iPS) cells, which have the ability to differentiate into any cell type found in the body. Recently, Pei and his colleagues at China’s Guangzhou Institutes of Biomedicine and Health took this technique a step further by converting iPS cells into functioning neurons.

Researchers like those at Guangzhou Institutes often utilize a process known as cell reprogramming to create iPS cells. In this process, adult cells, such as blood or skin cells, are reprogrammed by introducing genes that allow cells to differentiate into specialized cells, just like embryonic stem cells. Instead of utilizing blood of skin cells, Pei and his team formed iPS cells from human urine cells, giving them the same potential to differentiate into neurons that embryonic stem cells have.

However, Pei and his team are making it apparent that iPS cells can be far more advantageous than using embryonic stem cells. Compared to embryonic stem cells, which are derived from a 4-5 day old human embryo, iPS cells converted from urine cells are much more feasible considering the accessibility of urine. Furthermore, these iPS cells don’t pose the risk of developing tumors when transplanted into a living organism.

After forming iPS cells from urine cells, Pei and colleagues formed neural progenitor cells by introducing them to a neuron growth medium. These neural progenitor cells, or NPCs, are what give rise to neurons, and Pei’s team successfully cultivated functioning neurons in vitro with these NPCs.

a) Bright-field image of differentiated cells originated from NPCs made from human urine cells. From ““Generation of integration-free neural progenitor cells from cells in human urine.”

Their research points towards promising ends, and the Guangzhou Institute team has high hopes for future applications of their work. In their study, “Generation of integration-free neural progenitor cells from cells in human urine”, published at the end of last year in Nature Methods, Pei and his colleagues envisioned that their “protocols can be further applied to Human Urine Cells isolated from patients with neural disorders such as Parkinson’s disease, Alzheimer’s disease or other neurodegenerative diseases.” It seems possible that their vision could be realized, as the team has discovered that the iPS cells reprogrammed from urine developed at twice the speed of iPS cells made from blood or skin cells. Combined with the relative simplicity of collecting a urine sample from a patient, the use of human urine cells in therapies for neurodegenerative disease could become highly viable.

The most compelling piece of evidence, however, is what happened when the China-based team took their homegrown neurons and implanted them into a living specimen. Neurons that the team cultivated from human epithelial kidney cells were transplanted into the brain of a newborn rat, and these cells continued to function and differentiate. After four weeks, the cells maintained the signs of functioning neurons, without displaying any markers of tumor formation.

With a potentially safer, more abundant, and more personalized source of neurons, therapies for neurodegenerative diseases could be revolutionized in coming years, and its beginning to look like Pei and his team have stumbled upon a “gold rush” of their own.

Sources:
Brain cells made from urine -Nature Methods

Differentiation of hUiNPCs in vitro -Nature Methods

How to make a human neuron -Nature Methods

Alternative stem cell sources – University of Notre Dame, Initiative on Adult Stem Cell Research & Ethics

From Skin Cells to Brain Cells

Natalie Banacos — Wed, 13 Apr 2011 15:19:11 +0000

As much fun as I had exploring psychology last time I set out to write a blog post, this article from Science Daily caught my eye last week and I had to revert to my biology-related posting habit. Evidently, researchers at Oxford in the UK are using skin cells to grow induced pleuripotent stem (IPS) cells to use in their study of Parkinson’s Disease. What’s so useful about this technique is that skin cells are easily accessible, in contrast to the hard-to-reach tissues of the brain. With the skin cells obtained, the scientists plan to grow dopaminergic neurons and work on techniques for early detection of PD, perhaps finding ways to diagnose it before patients start showing symptoms. The skin cells will be from early-stage Parkinson’s patients, so they can be compared to the dopaminergic cells of healthy individuals to determine where things go wrong in the neurons affected by the disease.

Scientists at Stanford have recently grown neurons from stem cells created from the skin of a sixty-year-old Parkinson’s patient, whose disease is genetic in origin. From the skin cells, they were able to grow neurons that first acted like regular neurons should. The concern was how fast these Parkinson’s neurons would begin to show signs of the disease, as symptoms takes decades to show up in patients. Fortunately, “the culture dish is a pretty stressful place to be” according to Blake Byers, a Stanford graduate student working on the project. Applying selected toxins eventually brought the neurons to oxidative stress, and they began producing more of the proteins required to respond to such stress: proteins known as Lewy bodies – a phenomenon often coupled with Parkinson’s disease. These researchers are looking a bit more to the treatment side as an outcome for their studies, as Byers says, “By comparing neurons from patients with different forms of Parkinson’s disease, we may find commonalities or differences that will help to optimize future treatments for each patient.”

Using stem cells to investigate neuro-degeneration is not an entirely new thing, and there have been many interesting studies in the area. In 2008, researchers at M.I.T. grew IPS cells from mouse skin cells, and inserted them into the brain cavities of developing mouse fetuses, finding the cells still present and a functional part of the mouse brain once the animal was born. Then, they selectively eliminated dopaminergic neurons in the brains of rats, and observed a lack of coordination in the animals as a result. When they grew dopaminergic neurons from IPS cells and grafted them into the dopamine-lacking areas of the rats’ brains, eight of the nine rats showed motor improvement! Though the Parkinson’s model produced in rats was not exactly in line with human Parkinson’s, this study is a fascinating look at potential methods of future therapy. Luckily, the recent use of IPS cells grown from human skin cells provides a more accurate model with which to study the course of Parkinson’s disease and various ways to approach treatment.

Neurons With Symptoms of Parkinson’s Disease Created from Patient’s Skin Cells – ScienceDaily
Scientists create neurons with symptoms of Parkinson’s Disease from patient’s skin cells – physorg.com

Researchers Flesh Out Parkinson’s Treatment Using Skin Cells – Scientific American

Craig DA, Nguyen HT. “Adaptive EEG Thought Pattern Classiﬁer for Advanced Wheelchair Control.” 2007 Annal International Conference of the IEEE Engineering in Medicine and Biology Society, Vols 1-16 : 2544-2547 2007 -PubMed

A Peek at Parkinson’s: What’s New for the Old?

Margaret Mcguinness — Tue, 08 Mar 2011 17:26:54 +0000

With the Pancakes for Parkinson’s event at Boston University nearing, on April 2^nd, I thought it would be a good time to check up on the latest in Parkinson’s research.

Firstly, Parkinson’s Disease (PD) is a motor disorder that affects dopaminergic neurons of the brain, which are necessary in the coordination of movement. Onset is usually around age 60, starting with symptoms including tremor, stiffness, slowness of movement, and poor balance and coordination. While current treatments can help alleviate the symptoms in patients, none provide a cure.

Second off, the mission of the Michael J. Fox Foundation for Parkinson’s Research and other support groups is to find better treatments for those suffering from the disease. With the Baby Boomer generation entering late adulthood and old age, more research needs to be done to better understand the disease and help those with it find relief. Consider stopping by the GSU Alley for some pancakes to show your support for the Foundation and its cause next month!

Ranging from studying food intake to using technology, many approaches have been used in PD research.

FOOD

In a study released in February from the Harvard school of Public Health, flavonoids (citrin and Vitamin P), found in chocolates, citrus fruits, berries, and other foods, were speculated to reduce the risk of Parkinson’s Disease (PD).

The top 20% of males consuming these foods were 40% less likely to develop PD than the bottom 20%. While the overall flavonoid intake had no effect on women, a subclass of flavonoids called anthocyanins, which are primarily found in berries, did.

Study author Dr. Xiang Gao notes that this subclass has neuroprotective effects. Dr. Carlos Singer of UMiami’s Miller School of Medicine adds that the risk reduction “probably has to do with an antioxidant effect” because a lot of PD mechanisms deal with how nervous tissue handles oxidative stress.

Dr. Anna Hohler, a neurologist and professor at our very own, Boston University, was not involved in the study, but she comments on its benefits, saying that it “opens up a whole area of potential future studies examining other types of environmental effects on Parkinson’s.”

Hopefully, with more research we can determine whether these berries play a role in risk reduction. For now, Gao encourages us to eat berries anyway – they’re part of the reason why fruits and vegetables are so good for our health! Want to start a regular berry-eating habit? BU’s Mind and Brain Society is actually hosting another Miracle Berry event March 23^rd. Soon enough, you can reap the benefits of berries, AND have a taste-altering experience – find out how bitter foods can taste quite sweet when these berries intervene then!

DRUGS

Berries are not the only things that affect PD. Drugs, of course, do. One drug is the psychostimulant – amphetamine. According to a study released in February, amphetamines may increase the risk of PD, in contrast to the berries. Researchers found that those using the amphetamines Benzedrine or Dexedrine at some point in their lives were 60% more likely to develop PD compared to those who never used. Why? According to the report, amphetamines affect the release and absorption of dopamine, a neurotransmitter associated with PD development. More on the mechanisms causing this difference still need attention.

Another drug to consider is apomorphine, which is used to alleviate PD patients’ motor symptoms. Amazingly, this drug has also been found to improve short-term memory in mice with Alzheimer’s Disease, which, like PD, affects brain function. According to a study released in October, 2010 by Japanese researchers at Kyushu University, the drug reduced the levels of amyloid beta, a protein that reduces brain cell function; it led mice to improve their times in a swimming test conducted before and after the drug was injected.

The results, indicating improved memory function, “will lead to the development of a new treatment for Alzheimer’s disease,” says Associate Professor Yasumasa Oyagi. His group plans to perform clinical testing on human patients to develop a drug with few or no side effects (apomorphine can cause nausea and vomiting).

While not directly influencing PD patients, this development is inspiring; perhaps drugs used to treat other neurodegenerative diseases can help treat PD as well.

PROTEINS

In their study published March 4^th, Researchers at John Hopkins found that, when the parkin gene is mutated in genetically altered mice, the protein PARIS accumulates since its degradation is blocked. Excess decreases the production of PGC-1alpha, a protein that protects brain cells, such that unprotected cells die and PD advances.

“Of all the important changes that lead to the death of brain cells as a result of parkin inactivation, our studies show that PARIS is, without a doubt, a key player,” says Ted Dawson, M.D., Ph.D., of the Johns Hopkins Institute for Cell Engineering.

STEM CELLS

A press release March 3^rd announced that Stanford researchers used induced pluripotent stem cells to model PD. With the skin of a woman with a genetic form of PD, they derived neurons that replicated “some key features of the condition in a dish.” They hope to test treatments on and learn more about PD from these neurons.

TECHNOLOGY

A study published in September, 2010, demonstrates an approach to PD treatment through technology, specifically virtual reality. Researchers involved wanted to reduce “fall risk and difficulties with mobility, especially during complex or dual-task walking.”

Using virtual reality, they can better “incorporate principles of motor learning while delivering engaging and challenging training in complex environments.” At the end of the training, they observed a significant improvement in gait speed, particularly in walking, dual task, and facing overground obstacles. One month after the training, researchers still observed these effects. The group hopes to continue research on motor learning and fall risk reduction.

PSYCHOLOGY

From a review published in January, neuroscientists examined studies on Theory of Mind (ToM), “the ability to infer other people’s mental states,” in those with PD. They found “preliminary evidence that ToM difficulties may occur in PD patients,” particularly in the “cognitive component of ToM in the early stages of the disease.”

SOCIETY

Paul Green of Westport, CT was diagnosed with PD 17 years ago. Since then, he has searched for ways to slow its progression, finding some that have allowed him to live into his 80s. Now 87, he denies that symptoms like depression and tremor will occur.

Compiling his research, he wrote a booklet on his conclusion that progression can be slowed with “vigorous exercise.” Using this and his foundation Nevah Surrendah to Parkinson’s (inspired by Winston Churchill’s use of “nevah” in WWII), he aims to help others with PD.

He believes that with “prescription drugs, deliberate exercise and changes in nutrition and attitude they can enjoy a full life.” He continues, “What works for one person might not be as helpful for another. However, it’s vital that people ‘nevah’ stop trying to improve their physical, spiritual and emotional condition.”

Whether people eat more berries, exercise more, or cut down on amphetamines, they are making attempts to fight PD. Thanks to the research using so many different approaches, a lot has been discovered about the disease. However, it is quite clear that many more studies need to be carried out to affirm the conclusions above and better understand the mechanisms of PD. For now, with awareness and support of Parkinson’s Disease research, the goal is to find the best treatments for patients and most earnestly a cure.

Sources: Berries may offer sweet protection against Parkinson’s — Steven Reinberg of The Jackson Sun; Certain foods could reduce risk of Parkinson’s? Berry possible. – Tyler Moss of Northwest Indiana (NWI) Times; Parkinson’s drug ‘helped mice with Alzheimer’s’ – The Daily Yomiuri; Can Prescription Amphetamine Use Raise Parkinson’s Risk? – Stacy Lipson of Bloomberg Newsweek; Johns Hopkins Team Explores Paris; Finds A Key To Parkinson’s – Press release by Maryalice Yakutchik; Stanford scientists create neurons with symptoms of Parkinson’s disease from patient’s skin cells – Press release by Krista Conger; Virtual Reality for Gait Training: Can It Induce Motor Learning to Enhance Complex Walking and Reduce Fall Risk in Patients With Parkinson’s Disease? – Anat Mirelman, et al. from the Journals of Gerontology; Theory of Mind in Parkinson’s disease – Michele Poletti et al. from ScienceDirect; Westport man refuses to surrender to Parkinson’s – Karen Kovacs Dydzuhn of Westport News