Saccharomyces boulardii improves migration of new epithelial cells

The lifespan of healthy intestinal epithelia is generally accepted to be about 5 days.  These cells, once departed and sloughed off into the fecal stream, are replaced by newer, younger, healthier cells which proceed through the same life-cycle.  In the case of inflammatory bowel diseases (IBDs), in addition to inflammation/ulceration/tissue injury, the migration process of these new epithelial cells is stunted.  Since the replacement cells have trouble reaching their destination, damage to the intestinal lining is exacerbated.

A recent study -- published in PLoS ONE and open access if anyone wants to take a peek -- investigated the capacity of a nonpathogenic yeast to alleviate this stunted migration of new epithelial cells to the tips of intestinal villi (the fingers of tissue that protrude from the intestinal wall to create surface area for absorption).  Saccharomyces boulardii (Sb) is typically used to treat issues such as diarrhea, the idea being that it stimulates growth factors that help restore homeostasis to the gut.

This nigh-rockstar study strikes me because it is targeting a curative mechanism as opposed to a squelching of symptoms.  To achieve actual remission in IBDs, one has to pwn both inflammatory and repair dysfunctions.  The inflammatory component is predominantly targeted by the entourage of immuno-suppressants with which Crohns are so familiar.  Repair is seldom highlighted as it should be -- excepting methods of balancing gut flora.

The team of scientists in France, lead by one Frederic Andre, looked at the beneficial effects of Sb in both mice and an in vitro wound model (this is a strain of cultured epithelial cells which are attacked gently with a toothpick... rather cute).

The first major finding was that mice who were fed Sb for one week doubled new epithelial cell migration.  Only one downer for me in this study was that the mice were all healthy, with no in vivo IBD model for comparison.  Nonetheless quite encouraging, no?

The second conclusion was that the wounded cell line closed its wound (or, repaired its injury) by roughly 70%.  Their video supplement to this end is quite something.

The scientists conclude that Sb improves new epithelial migration both in vivo and in vitro.  Interestingly, the study suggests that increased migration is due to increased motility of cells and not to increased proliferation (the generation of new cells).  Sb may be stimulating this activity by secreting factors that stimulate  a target signaling pathway FAX/paxillin, which leads to several physiological changes in the intestinal epithelial lining that enable motility of new epithelial cells.

The thing about supplement studies such as this one is that they make me want to stop by the grocery and pick some up on my way home...


Canonici A, Siret C, Pellegrino E, Pontier-Bres R, Pouyet L, Montero MP, Colin C, Czerucka D, Rigot V, & André F (2011). Saccharomyces boulardii Improves Intestinal Cell Restitution through Activation of the α2β1 Integrin Collagen Receptor. PloS one, 6 (3) PMID: 21483797

increasing women in neuroscience

The Department Chair Training to Increase Women in Neuroscience (IWiN) is scheduled to meetin in Tucson, at the University of Arizona this April.  The workshop, funded by the National Science Foundation's ADVANCE program, is a three-year program aiming to increase the number of women on neurosciences faculty.  The participants of these workshops expect to leave them with tools to implement recruitment and advancement plans for women within their universities, and to disseminate the information they have gained in "echo" workshops at their institutions.

The IWiN workshops will be hosted in 2011 and 2012 at two of the graduate schools at which I may be a [woman] student at the time... depending on how interviews go at the end of this month.  Three of my four choice graduate schools are already participants of the ADVANCE program, which is not too shabby except that the missing institution has a ratio of approximately 1:3 women to men and does not facilitate an equity program in research.

I mention the IWiN workshops in response to a recent article in the New York Times discussing a nice array of statistics about the paucity of tenured female faculty, and women in the upper administrative echelons of science in general.  This was summarizing a study based out of UC Berkley.  The statistic that I thought was deserving of further attention in the New York Times report was this one:

"Tenured male scientists are considerably more likely to be married with children than tenured female scientists — 73 percent for men versus 53 percent for women. The report noted that among tenured science professors, women are nearly three times more likely to be single without children than men — 25 percent to 9 percent."

 The Berkeley article itself furthers this discussion beautifully, and as a woman weighing the possibilities of children and eventual faculty tenure (albeit, we're talking about ten years down the line), I highly recommend a read and consideration of the original research article:


Mary Ann Mason, Marc Goulden, Karie Frasch (2010). Keeping Women in the Science Pipeline Focus on Workplace Flexibility

in indirect support of the hygiene hypothesis

A recent study out of the University of Michigan Medical School suggests that the stomach bacterium Helicobacter pylori protects against inflammation caused by Salmonella in a mouse model of Inflammatory Bowel Disease (IBD).

This is surprising for two reasons: 1) IBDs occur primarily in the colon while H. pylori is active in the stomach, and 2) the H. pylori bacterium is regarded as dangerous gut flora and typically treated with antibiotics to avoid the development of stomach ulcers.

The findings of Higgins et al are equally unsurprising given the light that has been shed on helpful bacterial/parasitic gut balance by the Hygiene Hypothesis.  The Hygiene Hypothesis suggests that a modest intestinal hookworm population may stave off the excessive inflammatory response inherent to Crohn's disease, Lyme disease, asthma, rheumatoid arthritis and other conditions.  If this parasite whose reputation is built from its roles in epidemic illnesses in countries where sanitation is poor can, in small doses, help defend inflammatory diseases, then why couldn't the H. pylori bacterium as well?

There are currently no reports of an additive or destructive effect of both H. pylori and hookworm on gastrointestinal inflammation in humans, although it would be quite telling to see the results of their coincidence.  Patients from many H. pylori studies have been excluded from reports because they also shown signs of hookworm-related anemia (Vijayan et al 2007, as an example).  But this scientists wonders, because humans evolved almost symbiotically with both of these flora, if all of our immune systems would be better balanced were we not to wipe them both out completely.

A few thoughts from Dr. Higgins, one of the Salmonella study's researchers, can be found in an interview here.


Higgins PD, Johnson LA, Luther J, Zhang M, Sauder KL, Blanco LP, & Kao JY (2010). Prior Helicobacter pylori infection ameliorates Salmonella typhimurium-induced colitis: Mucosal crosstalk between stomach and distal intestine. Inflammatory bowel diseases PMID: 20976712

in which more evidence accumulates for utility of calcium channel blockers in treating Parkinson's disease

Neurodegeneration in Parkinson's disease is known to be specific to a group of dopamine neurons originating in the substantia nigra pars compacta (SNpc).  In  nearby region, the ventral tegmental area (VTA), dopamine neurons are all but unaffected by disease progression.  This selectivity has generated great interest from the PD research community.  In  a study out of Dr. D. James Surmeier's lab at Northwestern University, this selectivity was suggested to be related to calcium channel activity.

 Neural pacemaking, or the rhythmic signalling common to neurons in the motor circuit, involves the influx of calcium into the cell.  Pacemaking in juvenile SNpc dopamine neurons is similar to neurons in the VTA.  However, in mature SNpc neurons pacemaker firing opens many more L-type calcium channels than in VTA neurons.  This allows for greater influx of calcium to the cell, and puts a greater burden on the mitochondrial system in order to pump it out, fostering oxidative stress.  Therefore, basal oxidative stress is thought to be significantly higher in SNpc compared to VTA dopamine neurons.

The Surmeier team wanted to confirm the importance of the L-type calcium channel in producing the differences in oxidative stress levels between SNpc and VTA neurons.  In order to do this, they used a genetic knockout model of DJ-1 (or Park7), the popular gene linked to occurance of familiar Parkinson's disease.

In a beautiful study, they recorded intracellular calcium oscillations and oxidation of mitochondrial matrix proteins from SNpc dopamine neurons in mice with or without the DJ-1 gene, and found that oxidative stress was greater in SNpc neurons in DJ-1 knockouts compared to wild type.  They also showed that pretreatment with isradipine, an L-type calcium channel agonist, kept DJ-1 knockout oxidative stress levels near wild type levels.

The study also suggests that mitochondrial uncoupling protein (UCP) expression is greater in SNpc dopamine neurons compared to VTA, resulting in more frequent mitochondrial 'flickering', or transient depolarization.  In DJ-1 knockout mice, UCP expression was lower, suggesting that UCP expression in SNpc dopamine neurons contributes to oxidative stress.

Collectively, the restuls of the study indicate that high calcium entry to SNpc dopamine neurons through L-type channels during pacemaking activity leads to selectively elevated oxidative stress.  In turn, these SNpc dopamine neurons are made more susceptible to toxins, aging and the degenerative effects of DJ-1 mutations.  Several calcium blockers are currently used to treat conditions like cardiomyopathy and kidney disease, btu the current study suggests their use in Parkinson's disease in order to protect against oxidative stress to which these mature neurons are so vulnerable.


Guzman JN, Sanchez-Padilla J, Wokosin D, Kondapalli J, Ilijic E, Schumacker PT, & Surmeier DJ (2010). Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature, 468 (7324), 696-700 PMID: 21068725

an instance of misconstrued media reporting: placebos

A most recent example of the media mis-representing scientific findings is the recent NPR report on placebos being equally effective in IBS patients as "the strongest prescription drugs", even when the patients knew that they were being given the placebo.  This coverage was a translation of a study out of Harvard Medical, and published in PLoS ONE.


The study, termed "honest placebo", didn't actually eliminate the deception for which placebo studies are renowned.  In the methodology, the researchers report telling the patients who received placebo treatment that “placebo pills, something like sugar pills, have been shown in rigorous clinical testing to produce significant mind-body self-healing processes.”  By this design, the patients may have received a similar benefit to what they would have experienced if they had expected that they were being given a strong prescription drug.  The patients were given the impression that the placebo would help them.  What would have contributed even greater meaning to this study is an additional group who were told that they were receiving a placebo drug, but not told that it was expected to help them.


As many of the comments on the NPR report echo, a strong component in placebo studies is the idea of holism and self-healing.  Dr. Ted Kaptchuk, a co-investigator in the Harvard study, states in his interview that the healing factor was assumed to be the "self-healing ritual" of dosing oneself twice daily, even with a placebo.  This scientist would suggest that self-healing is as likely to take place due to the belief that a placebo had been reported helpful as it is to be due to the ritual of pill-taking.


The great value of this study's conclusions is lost in the media translation: there is healing potential in having the expectation that your therapy will work. 
 NPR does the courtesy of acknowledging that "placebos don't shrink tumors or stop multiple sclerosis in its tracks".  However, particularly for conditions such as IBS, which have consistently shown to be negatively effected by stress and proactive treatment, this study's findings are important to treatment development.


Ted J. Kaptchuk, Elizabeth Friedlander, John M. Kelley, M. Norma Sanchez, Efi Kokkotou, Joyce P. Singer, Magda Kowalczykowski, Franklin G. Miller, Irving Kirsch, Anthony J. Lembo (2010). Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome PLoS

VEGF-B as a therapeutic intervention for Parkinson's disease

Since it was discovered that the brain had tremendous neuroregenerative potential, growth factors have been highly speculated as therapeutic tools.  The vascular endothilial growth factor (VEGF) family, and particularly VEGF-B, has recently been distinguished as having a neuroprotective role in the Parkinsonian brain.

Carolina Hagberg et al. published the findings in Nature Letters earlier this year that VEGF-B was tightly co-expressed with several mitochondrial genes, suggesting a role for this growth factor in metabolism.  VEGF-B was specifically found to regulate endothilial fatty acid transport (uptake) proteins, and thus, the uptake of fatty acids into peripheral and heart muscle, and brown adipose tissue.  The co-expression of VEGF-B and mitochondrial proteins suggests a coordination of endothilial lipid uptake and mitochondrial lipid use, which is why it is an attractive intervention for PD, wherein it is thought that dopaminergic neurons die by dysfunction of mitochondrial metabolism.

This mechanistic information provides support for work lead by Torsten Falk at the University of Arizona suggesting a role for VEGF-B in the Parkinsonian brain.  In a 2009 study, a midbrain cell culture showed upregulation of the VEGF-B gene following treatment with rotenone (a pesticide specifically toxic to dopaminergic neurons, and commonly used in non-primate animal models of PD).  Additionally, application of exogenous VEGF-B to cell cultures resulted in neuroprotection from rotenone toxicity.

More recently, Falk et al. have shown exogenous VEGF-B to be neuroprotective in vivo.  From a 2006 study by Sun et al., intraventricularly administered VEGF-B restored neurogenesis to wild-type levels in VEGF-B knockout mice.

In corroboration with the Hagberg study, there is a strong suggestion that VEGF-B may be neuroregenerative via direct effect on mitochondrial function.  Correlative studies associating VEGF-B expression with midbrain mitochondrial un-coupling proteins, Complex I, or apoptotic cascades remain to be seen.  Additionally, there are no reports of VEGF-B's capacity to be neurorestorative, or slow dopaminergic neurodegeneration in a progressive PD model.


Hagberg, C., Falkevall, A., Wang, X., Larsson, E., Huusko, J., Nilsson, I., van Meeteren, L., Samen, E., Lu, L., Vanwildemeersch, M., Klar, J., Genove, G., Pietras, K., Stone-Elander, S., Claesson-Welsh, L., Ylä-Herttuala, S., Lindahl, P., & Eriksson, U. (2010). Vascular endothelial growth factor B controls endothelial fatty acid uptake Nature, 464 (7290), 917-921 DOI: 10.1038/nature08945

T. A. FALK, X. YUE, S. ZHANG, S. J. SHERMAN (2010). Evidence for neuroprotection after treatment with Vascular Endothelial Growth Factor-B in vivo in the 6-hydroxydopamine rat model of Parkinson’s disease Society for Neuroscience 2010 Abst.

Sun, Y., Jin, K., Childs, J., Xie, L., Mao, X., & Greenberg, D. (2006). Vascular endothelial growth factor-B (VEGFB) stimulates neurogenesis: Evidence from knockout mice and growth factor administration Developmental Biology, 289 (2), 329-335 DOI: 10.1016/j.ydbio.2005.10.016

SfN 2010 Take-aways

Things that I learned from posters, presentations and lectures at SfN this year will play themselves out in my research and career direction, but there were other notables which were not so directly translatable.  Here are my not-necessarily-scientific take-aways from SfN 2010:

1.  Had anyone told me growing up that learning multiple languages with any degree of volubility would be very important in my communication with other scientists, I would have put more effort into Spanish, German and French.  Four years of Latin does me worlds of good in reading, but in deciphering various accents and breaking language barriers... repetition and speaking loudly were my only saving tools last week.  It is very humbling that all of these wonderful minds, to whom English is a second language, have learned it so fluently.

2.  Although it was immense fun to spend a week on a yacht in a nearby harbor, I think that I would have gotten more out of staying closer to the convention center.  By the time 7pm approached and I had mosied back to my boat, had a bite to eat (on those nights when we did not go out to eat) and relaxed, another twenty minute drive back to the convention center area for any of the satellite events was less appealing.  ... and I do regret missing out on some of those -- thank goodness for Neuroblogger reports!

3.  Limiting my content was certainly helpful, and the best approach for me.  What happened was that I made sure that I got to everything on my list, and then ventured out into other subfields (olfaction, methodologies, learning and memory).  Next year, I think I will venture even further, as I still limited this extended content to its relation to my methodologies, or my circuits, or my disease.

4.  Taking two afternoons to explore the city was essential.