Stereological Study Reveals Neuron and Glia Proliferation in Hippocampus of Lithium-Treated Mice

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The optical fractionator probe was used to quantify the number of neurons and glia in the dentate gyrus

Doctors have used lithium to treat patients with bipolar disorder since the 1970s. Known for its efficacy in stabilizing patients’ moods by regulating manic episodes, lithium is also associated with a decreased risk of suicide. But while this naturally occurring element is the most widely prescribed medication for those suffering from bipolar disorder, scientists still have much to learn about how lithium physically affects the brain.

A recent study published in the journal Bipolar Disorders adds to the growing body of evidence that says lithium contributes to cell proliferation in parts of the brain. Conducted by scientists at the University of Mississippi and the VU University Medical Center in Amsterdam, the study revealed an increased number of neurons and glia, and increased astrocyte density in the dentate gyrus of lithium-treated mice versus controls treated with a placebo.

Using the optical fractionator probe in Stereo Investigator, the researchers quantified the number of Nissl stained neurons and glial cells, and calculated astrocyte density. The results showed twenty-five percent more neurons and twenty-one percent more glia in the denate gyrus of lithium-treated mice. They also performed a stereological examination of another brain region – the medial prefrontal cortex (mPFC), but did not witness significant differences between lithium-treated and control mice in this area.

“In this study, particular cortical regions, ie. the fascia dentata in the hippocampus and the mPFC in the cerebral cortex needed to be selected in histological sections of the mice brains,” explained Dr. Harry B.M. Uylings, “therefore the stereological counting procedure applied was the best one. Stereo Investigator greatly assisted in the counting of cells, and the software’s excel data-output was especially beneficial.”

According to the paper, the findings present a more detailed picture of lithium-induced alterations in the dentate gyrus cellular phenotype than previously available, and provide the first evidence for lithium-induced increases in glia and astrocytes.

The authors also explain that while cell number increased in the dentate gyrus of lithium-treated mice, the region’s overall volume as well as that of the greater hippocampus was unaffected by the element. The volume of the dentate gyrus and the hippocampus as a whole was measured with the Cavalieri method in Stereo Investigator.  The researchers describe the dissociation between cell proliferation and volume as “an interesting observation that warrants further investigation.”

Rajkowska, G., Clarke, G., Mahajan, G., Licht, C.M., van de Werd, H.J., Yuan, P., Stockmeier, C.A., Maji, H.K., Uylings, H.B., Differential effect of lithium on cell number in the hippocampus and prefrontal cortex in adult mice: a stereological study. Bipolar Disord. 2016 Feb;18(1):41-51. doi: 10.1111/bdi.12364.

Genetic Mutation Accelerates CTE Pathology

Phosphorylated tau pS422 immunoreactive profiles in the cortex of P301Smice after repetitive mild TBI. Image courtesy of Dr. Leyan Xu.

Phosphorylated tau pS422 immunoreactive profiles (dark brown) in the cortex of P301S mice after repetitive mild TBI. Image courtesy of Dr. Leyan Xu, Department of Pathology, Johns Hopkins University.

Over the course of a football game or a boxing match, athletes may experience a series of mild concussions. Some of these athletes develop a condition known as chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by the build-up of abnormal tau protein that eventually leads to dementia. But not every athlete develops CTE after repetitive mild traumatic brain injury, and scientists think genetic factors are involved.

In a recent study, researchers at the Johns Hopkins University School of Medicine found that the density of abnormal tau protein increased exponentially in mice that had a genetic mutation thought to cause neurodegenerative diseases. Their findings contrast with previous studies of mice without genetic mutation, where abnormal tau protein build-up did not occur. This evidence leads the scientists to infer that genetic factors play a role in the onset of CTE.

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Satellite Symposium at SfN: Enhancing the Reproducibility of Your Research Results with Stereology

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Recent headlines decry the alarming amount of irreproducible data in published research papers. MBF Bioscience is hosting a symposium addressing the topic on Sunday, October 18 at 6:30pm entitled “Quantitative Microscopy: Enhancing the Reproducibility of Your Research Results with Stereology.” This symposium, which is a satellite event at the annual Society for Neuroscience meeting, will address how researchers can use stereology to obtain accurate, reproducible data about their histological tissue specimens to drive meaningful discovery by the scientific community at large.

It will be an evening full of engaging speakers with significant expertise in various aspects of stereology, including: stereology theory, the application of stereology in neuroscience research, and why some funding agencies require stereology. Attendees will have a chance to interact with the speakers during the question and answer session following the presentations.

Stereology is the gold standard method for quantifying the number of cells, length of fibers, and the area and volume of structures or regions in tissue specimens. Attend this symposium to learn how it can help you obtain accurate, reproducible data for your research study.

Interactive Probe Selector for Stereology

probe selectorSelecting a probe for stereology is an important decision that should be made before you section your tissue. Some probes require thick sections and others require thin sections. We created an Interactive Probe Selector to help you choose the appropriate probe for your research. Give it a try and let us know what you think.Area and Volume Estimation in Stereo Investigator

Upcoming webinar: Q&A session about stereology

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Do you have questions about stereology? MBF Bioscience invites you to a Q&A webinar about stereology with our staff scientist, Dr. Susan Tappan, on Wednesday, July 24th at 12:00 pm (EDT). This webinar, like all webinars from MBF, is free of charge. All you need to do is bring your questions about stereology theory, stereology experimental design, or Stereo Investigator software. You can also submit your questions in advance to the webinar coordinator, Kristin, at kristin@mbfbioscience.com.

Click here to register for the webinar.

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Or, watch previous webinars on our website.

MBF Bioscience attends the International Conference of the Society of Neuroscientists of Africa (SONA)

Dr. Jose talks with a customer at the MBF Bioscience booth

Dr. Jose talks with a customer at the MBF Bioscience booth

The 11th International Conference of the Society of Neuroscientists of Africa (SONA) was held in Rabat, Morocco from June 7-12, 2013. Neuroscientists from Africa and around the world gathered to discuss the latest advances in Neuroscience. The program filled with lectures, symposia, posters, and oral sessions was sponsored by the International Brain Research Organization (IBRO) and the Society for Neuroscience (SfN).

Neuroscientists gather at the SONA conference held in Rabat, Morroco

Neuroscientists gather at the SONA conference held in Rabat, Morroco

Dr. Jose Maldonado, Head of Operations for MBF Bioscience Latin America and Africa, attended the conference. “This year’s SONA meeting in Morocco was a great opportunity to introduce MBF Bioscience Inc. to the neuroscience community in Africa. Quantification of anatomical regions, as well as cell populations, was a common theme among the posters. It was a dynamic meeting and I look forward to attending again in the future,” said Dr. Maldonado. Attendees who stopped by the MBF Bioscience booth were particularly interested in Stereo investigator, MBF’s system for stereology that gives accurate, unbiased estimates of the number, length, area, and volume of cells or biological structures in tissue specimens.

Thank you to everyone who attended the conference and visited us at our booth.

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Researchers at Stanford use confocal stereology to study neurodevelopment

A Stereo Investigator system for confocal stereology was installed in Dr. Michelle Monje’s lab in the Department of Neurology and Neurological Sciences at Stanford University School of Medicine. Dr. Monje and her lab members will use the system to investigate the molecular and cellular mechanisms of postnatal neurodevelopment.

Dr. Julie Korich, staff scientist at MBF, installed Stereo Investigator on a Zeiss laser scanning confocal microscope and trained the lab members on how to use the system.

From top left: Chris Mount, Grant Lin, Ingrid Inpma, David Purger From bottom left: Elizabeth Qin, Viola Caretti, Lauren Wood

From top left: Chris Mount, Grant Lin, Ingrid Inpma, David Purger
From bottom left: Elizabeth Qin, Viola Caretti, Lauren Wood

During the training, Dr. Korich discussed how Stereo Investigator integrates with Zeiss’ microscope software, explained the Cavalieri probe for estimating regional volume, and showed the lab how to use Stereo Investigator to collect confocal image stacks in the systematic and random way that’s necessary for unbiased stereology. She also explained how to count cells from those image stacks and from 3D virtual slides with Stereo Investigator on a computer away from the microscope.

Click here to learn more about how researchers are using Stereo Investigator in their labs.

UCLA Scientists Count Cells with Stereo Investigator in Study Identifying Compensating Regions in Brain Damage

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If one area isn’t working, another part can step in. Plasticity is one of the brain’s most beautiful attributes. Recent research has documented the organ’s ability to compensate in the face of damage, and now a new study identifies a key region for compensation when the damage occurs in the hippocampus.

The region is the medial prefrontal cortex (mPFC). It’s an integral part of the hippocampal-prefrontal-amygdala circuit involved with memory formation – specifically with contextual fear memories. In their study, published last month in Proceedings of the National Academy of Sciences, researchers at the University of California, Los Angeles identify a microcircuit in the mPFC that can encode memories when the dorsal hippocampus is damaged.

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Increased Choline During Pregnancy Improves Learning in Down Syndrome Mice

DCX Cells Counted With Stereo InvestigatorObstetricians and midwifes have long hailed the benefits of folic acid during pregnancy. Now new research offers evidence that choline is another important nutrient for the developing fetus. Found in foods like eggs and cauliflower, choline is known to aid healthy liver function. But in the past few years, studies have shown that the nutrient also plays a role in brain development. One recent study by Velasquez and colleagues claims that increased choline during pregnancy may offer a possible therapy for Down syndrome.

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Stereo Investigator Helps Scientists Assess Damage in Rat Model of Ischemic Stroke

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A stroke patient is rushed to the hospital. Deprived of oxygen-rich blood, brain cells have already died, and more damage will probably occur in the hours and days to come. But researchers at the University of South Florida and the University of Padova in Italy say a two-part package administered through the body, rather than directly into the brain, may be the key to staving off some of the cell death that takes place after a stroke.

In their study, published in the Journal of Enzyme Inhibition and Medicinal Chemistry, the scientists saw a smaller region of damage in a rat model of focal cerebral ischemia, when the rats were treated with a combination of an anesthetic and a Caspase-3 inhibitor – a drug that suppresses a protein involved in brain cell death.

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