Stanford Scientists Render Mouse Brain Transparent, Offering New Possibilities For 3D Analysis

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The importance of studying the brain in three dimentions is something we understand at MBF Bioscience. Every day scientists around the world use our products to reconstruct neurons and analyze brain cells in 3D. That’s why we’re excited to hear about the new possibilities for whole brain analysis coming out of Dr. Karl Deisseroth’s lab at Stanford University.

A press release issued last week describes a whole-organ imaging process called CLARITY that made a postmortem whole mouse brain transparent.

Continue reading “Stanford Scientists Render Mouse Brain Transparent, Offering New Possibilities For 3D Analysis” »

MBF Labs Contributes to Recent PLOS Article on New Mouse Model for Huntington’s Disease

 

Stereologic volume estimation of the striatum (caudate putamen and nucleus accumbens) confirms changes observed using MRI volumetry in zQ175 knock-in mice.

Stereologic volume estimation of the striatum (caudate putamen and nucleus accumbens) confirms changes observed using MRI volumetry in zQ175 knock-in mice. Stereological analyses showed significant decreases in neuron numbers in homozygous zQ175 knock-in mice aged 4.5 and 10 months (13% and 15% respectively) as compared to age-matched wild-type mice

There is very little known about Huntington’s disease (HD), a fatal neurodegenerative disease leading to total physical and mental decline that affects 30,000 Americans today.

Researchers have been developing transgenic mouse models to mimic human HD. A new model, the zQ175 knock-in, developed by Menalled et al. (2012) appears to more closely mimic human HD progression in the zQ175 KI than previous mouse models.

A recently published paper (co-authored by MBF’s President, Jack Glaser, and Staff Scientist Dr. Susan Hendricks) confirms the behavioral phenotypes reported by Menalled, and extends the characterization to include brain volumetry, striatal metabolite concentration, and early neurophysiological changes. For this study, MBF Labs used Stereo Investigator to quantify neural loss and regional volumetric changes. These changes validate the similarities between HD progression in humans and HD-like progression in zQ175 KI mice.

With this new mouse model, researchers might be able to considerably improve their understanding of the disease to find ways to temper HD progression.

Read the full paper “Characterization of Neurophysiological and Behavioral Changes, MRI Brain Volumetry and 1H MRS in zQ175 Knock-In Mouse Model of Huntington’s Disease” on PLOS.

 

References:

Heikkinen T, Lehtimäki K, Vartiainen N, Puoliväli J, Hendricks SJ, et al. (2012). Characterization of Neurophysiological and Behavioral Changes, MRI Brain Volumetry and 1H MRS in zQ175 Knock-In Mouse Model of Huntington’s Disease. PLoS ONE 7(12): e50717. doi:10.1371/journal.pone.0050717

Menalled LB, Kudwa AE, Miller S, Fitzpatrick J, Watson-Johnson J, et al. (2012) Comprehensive Behavioral and Molecular Characterization of a New Knock-In Mouse Model of Huntington’s Disease: zQ175. PLoS ONE 7(12): e49838. doi:10.1371/journal.pone.0049838

Meet the Team: Susan Hendricks, Ph.D.

Name: Susan Hendricks, Ph.D.

Position: Staff Scientist

How long have you been working at MBF Bioscience? Five years.

What is your research area of interest? My area of interest is developmental neuroscience. I did my dissertation research on the development of the gustatory system and worked on the early development of the auditory system. I’m fascinated by how newly generated neurons figure out where they are supposed to be and what they are supposed to do. Now, I help others attain their research goals. It’s great to have a chance to be broadly interested in everything from nematodes to stroke, and from software code to microscope hardware.

Describe what you do: My days at MBF generally balance grant activities and data collection for MBF Labs, with a side of educational development thrown in for good measure. As grants manager, I collect data to support our research aims from funded NIH SBIR projects (such as automated neuron reconstruction). My first grant project at MBF Bioscience was for software to create and share digital 3D representations of histological slides. This research project is coming to a close and we’re about to launch the product that was the focus of those 5 years of effort. It’s so exciting to be able see the research go from theory to practice. I hope that Biolucida is as helpful to other researchers as I think it will be. I also run the day-to-day operations of MBF Labs, our contract research organization (CRO). We perform data collection and analysis for foundations, pharmaceutical companies, and academic researchers. It is so fulfilling to be able to devote a good portion of my job to doing traditional research.

What’s your favorite thing about working at MBF? Every day is different. I could spend my day working on an educational webinar, analyzing the stereological data from MBF Labs, working with the software developers to make our data collection more efficient, and finish up by chatting with researchers about experimental design questions or things they would like to see in the software.

How do you spend your weekends? Snowboarding in winter. Hiking with my dog Moxie in summer.

What was the last vacation you took? My honeymoon to Belize!

Register for the MBF Bioscience Instructional Webinar: “New Features in Version 10 Neurolucida and Stereo Investigator” conducted by Dr. Hendricks, Thursday, February 24.

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Need Help With Stereology? Consider an MBF Labs Pilot Study

by Susan Hendricks, Ph.D.

Stereology is a powerful tool that can reduce your workload and provide accurate, unbiased quantification. Unfortunately, stereology is often not the most intuitive method for the uninitiated. If it isn’t done properly, the results you attain may not be accurate. Here’s where we can help. Not only do we make Stereo Investigator, the most cited software for stereology, but now we’re offering to do your work for you. Send us your slides, and we’ll complete a comprehensive pilot study for you; providing an objective analysis of your tissue thickness and staining penetration, outlining sampling parameters and counting procedures, and providing you with the knowledge and confidence you need to collect the remainder of the data yourself. Our staff includes experienced Ph.D. research scientists who are experts with stereology methodology, our software, and who have demonstrated experience in neuroscience research applications.

Using a technique created at MBF and adapted from Slomianka and West (2005), we will calculate an adequate sampling fraction based on the section thickness, section interval, and the frequency of the objects to be counted within your tissue. We can also empirically determine the appropriate guard zones for your tissue. This data will be provided to you with the return of your slides in a report detailing how the parameters were chosen. Additional support as you begin your work is also available; we can walk you through your first counting procedure or even audit your work to ensure that data collection is proceeding as expected. Confidence in the technique will translate to confidence in the results.

Consider using our pilot study service as a way to optimize and streamline the quantification for all the animals in your study. And by using MBF to acquire the data of your pilot study, you are saved the time and labor involved in oversampling, to free you and your staff to complete other important experiments. Our research staff scientists and stereology technicians will work with you to outline the histology requirements for your experiment. Based on your hypothesized result, the number of animals needed for the pilot study will be determined. Do you expect to see a large, robust difference between control and experimental groups? Provide a subject from each group to ensure that the sampling is as efficient as possible. Need to remain blind to condition? The stereology pilot study should be performed, at a minimum, on the group in which you expect the fewest number of objects. This will guarantee that enough data is collected for the remainder of the subjects in the study.

A properly designed stereology pilot study will reduce time, effort, and costs for the overall experiment by optimizing the sampling parameters to identify how many sections are needed (and therefore generated and stained) to obtain a result with adequate precision.

Of course, if you want to outsource your complete study, we would be glad to help you with that as well.

For more information, visit mbflabs.com.

Citation: Slomianka L and West MJ (2005) Estimators of the precision of stereological estimates: an example based on the CA1 pyramidal cell layer. Neuroscience. 136(3): 757.

Susan Hendricks is a staff scientist at MBF Bioscience.

First published in The Scope, summer 2008.