Saturday
May032014

I smell a rat!

Turns out the rat smells you, too. Rodent behavioral studies are a cornerstone in neuroscience, but these experiments are notoriously difficult to conduct and often their results cannot be independently reproduced. A new report in Nature Methods this week sheds light on a major confound that may explain some of this variability. The authors found that mice and rats are very sensitive to the cocktail of odors produced by males, including unfamiliar males of the same species as well as guinea pigs, cats, dogs, and even human investigators! The scent from T-shits worn by human men, but not women, was sufficient to significantly affect rodent behavior in multiple tests of pain and anxiety. The effects are thought to result from stress-induced analgesia, an innate response to predator and competitor odors. In accordance with this model, mice exposed to human males or their T-shirts had greatly elevated corticosterone levels, elevated body temperature, and induction of immediate-early genes in the pain-processing neurons of the spinal cord. The authors caution that these effects may extend beyond behavioral analyses and may impact the tissues obtained from live rodents euthanized by either male or female experimenters. Incredibly, this whole study was initiated based on the anecdotal reports from lab personnel that mice failed to show pain behaviors when certain (male) investigators were present during the experiment. You can read the full report here: http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.2935.html

-Emily

Monday
Apr072014

Street view for the Brain: mapping the connectome

The race to understand the human brain is vaguely reminiscent of that to map the human genome 10 years ago. Since last year’s presidential announcement of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, there seems to be an omnipresent interest in understanding the complexities of the mind. Similar to the human genome project, there is a major effort to demystify the brain by creating a map of the underlying connections and circuitry—the connectome. A clear reference picture of how things look and work when they are functioning properly in a healthy human brain affords the ability to identify differences that arise with damage and disease. Although this may sound like a straightforward task, you must consider the number of variables involved: mapping 80+ billion neurons, 10,000+ neural connections, throughout each stage of development, learning and aging - it is an image of a dynamic process. Here at the Martinos center, scientists are hammering away at the human connectome using various MR-based imaging tools like diffusion tractography, which traces axonal fiber bundles throughout the brain indicating the path connecting functionally-related regions.

Animal models offer the advantage of manipulability and permit much more invasive techniques, which scientists are using to create a “mesoscale” connectome map. Researchers at USC (www.mouseconnectome.org) and the Allen Brain Institute (www.brain-map.org) are creating atlases of individual axonal projections by injecting anterograde/retrograde tracers and fluorescent protein producing virus, respectively, directly into specific brain regions. By following the path of the tracer or the virus, they can define the network of potential connections each neuron can make within the brain. Both of these projects take a systematic approach, breaking the brain down into a navigable, albeit massive, data sets. The best part being that these data are publically available online for use by other scientists- or for anyone to peruse! Both of these studies were recently published and will surely serve as an invaluable resource during continued efforts to understand the brain and learn to repair damages to it.

MAPPING THE MOUSE CONNECTOME

a, The data generation and processing pipeline. QC, quality control. b, The two main steps of informatics data processing: registration of each image series to a 3D template (upper panels) and segmentation of fluorescent signal from background (lower panels). c, Distribution of injection sites across the brain. The volume of the injection was calculated and represented as a sphere. Locations of all these injection spheres are superimposed together (left panel). Mean injection volumes ( ± s.e.m.) across major brain subdivisions are shown (Image from Oh et al, 2014)

References

SW Oh et al. “A mesoscale connectome of the mouse brain,” Nature, 000, 1-8, 2014. 

www.brain-map.org

 

B. Zingg et al., “Neural networks of the mouse neocortex,” Cell, 156:1096–1111, 2014.

www.mouseconnectome.org 

Wednesday
Mar192014

Drug development for Hep-C

A few years ago, I was in loop with the different competitions going on in the Pharma-world in the race to come up with a cure for the debilitating Hep-C virus. Hep C is simply a virus that destroys the fabric of the Liver, living its victims unable to utilize their Liver for its important functions. The competition was so much, that bigger pharma companies were purchasing smaller drug development companies that they deemed closer to the prized possession of the remedy. It turns out that, there was a lucky winner in the name of “Gilead”. For folks who don’t know much about Gilead, it is a Pharmaceutical company based out of Foster city, California. They develop single tablet regimen for viral diseases that are contagious.

The prized possession part of this write-up, comes in play with the FDA approval of the recently approved single tablet for Hep-C called Solvadi. Solvadi works simply by disrupting the replication mechanism of the Hep-C virus, for other drug regimen to cure the liver. Gilead deems its prized possession has a tremendous breakthrough. It is a tremendous breakthrough. So, Gilead has decided to sell this new drug that could save the lives of 3 million Americans at $1000 per pill. A standard treatment which they asserted will take 12 weeks would cost a whopping $84,000. If a second round of treatment with this drug is needed by a patient, that patient should be ready to cuff out $168,000.

It will be interesting to see how this pricy medication plays out with the health insurance companies. More importantly, it will be interesting to see how other drug development companies react to this gutsy move by Gilead. I am only left with the question “is this going to help shine the light on the pricey tags of drug development, and would it bring about the restructuring of this industry through more regulation.”

Ehimen A

Friday
Mar072014

Voice-sensitive region in the dog! 

...reported by the authors of the first fMRI study comparing humans and a non primate species 

Andics and colleagues conducted a study looking at how humans and dogs (who notably share a similar social environment) respond to human vocalizations, dog vocalizations as well as nonvocal environmental sounds.

The study's major finding is that dogs, just as humans and non-human primates, have a voice sensitive area (= a region that responds most strongly to conspecific sounds and less to heterospecific sounds or nonvocal sounds). In dogs, this region was located near the temporal pole, in a similar region as the anterior human voice area.

In addition, the authors observed regions sensitive to emotional valence in both species.

The authors also found important differences across species, which I found very interesting:

In dogs, of all auditory voxels: 39% responded to dog vocalizations, 13% to human vocal sounds and 48% to non vocal sounds

In humans, of all auditory voxels: 87% respond to human vocalizations, only 10% to dog vocalizations and a mere 3% to environmental non vocal sounds. This illustrates well the central role played by human vocalizations!

This study has many people discussing attributes of man's best friend… and scientists thinking about future studies.

Reference:

Andics et al., Voice-Sensitive Regions in the Dog and Human Brain Are Revealed by Comparative fMRI, Current Biology (2014), http://dx.doi.org/10.1016/j.cub.2014.01.058

Nicole

 

Saturday
Feb222014

What could be done with your brain once you no longer needed it?

A subject, taboo for some, comes to mind this week having visited the Lieber Institute for Brain Development in Baltimore, Maryland on the edge of the Johns Hopkins Medical Campus.

Scientists at the Lieber Institute have amassed a remarkable resource in a collection of over 1,000 brains from humans with a range of brain diseases: schizophrenia, bipolar disorder, depression – even anorexia nervosa.

Using high-tech sequencing methods, huge datasets of genetic sequence information (DNA and RNA) from focused regions of the brain are compared in order to better understand normal brain function, changes that occur in development and importantly, the potential causes of brain disease.

An established Brain Tissue Resource Center at Harvard's McLean Hospital has provided a similar 'bank' of tissue to researchers around the US and globe.  This resource has been used to resolve many important findings from post-mortem brain that serve as the basis for developing the next critical questions in neuroscience and psychiatric disease.

This is quite different from the techniques we explore at the Martinos Center, devoted to imaging the brain IN VIVO.  Both methods serve a critical role in advancing medical science for the benefit of human health, but only one requires the donation of part of your body once you have died.

Tissue donation, including brain donation is a personal choice, but its importance cannot be understated towards understanding how the brain works and how, for future generations, brain dysfunction can be better addressed through medicine.

Links below are to a news article on the Lieber Institute's brain collection, the Harvard Brain Bank, and the National Institute on Aging which continues to build a collection of Alzheimer's disease patient brains.

Think it over,
-A
-------------------------------------
Lieber Institute Brain Collection
http://www.baltimoresun.com/health/maryland-health/bs-bz-lieber-institute-expanding-20130720,0,2353528.story

Harvard Brain Tissue Resource Center, McLean Hospital
http://www.brainbank.mclean.org/

Nationial Institute on Aging Alzheimer's Brain Bank
http://www.ninds.nih.gov/research/parkinsonsweb/brain_banks/brain_biospecimen_repositories.htm