It’s Not You, It’s Your Hormones. Scientists Study Estrogen’s Role in Stress.

Scientific research shows that women are twice as likely as men to develop stress disorders. Why are women more sensitive than men to stress? A recent research study presents new evidence that estrogen could play a role.

The symptoms of disorders like major depressive disorder and post traumatic stress disorder lead neuroscientists to speculate that a dysfunction occurs in the way the medial prefrontal cortex connects to the amygdala–regions of the brain associated with the regulation of memory and behavior. Following research published in 2009 determining resilience against changes in dendritic morphology in this region in male rats, scientists at the Mount Sinai School of Medicine turned their focus to female rats. They discovered unexpected changes in dendritic length and spine density to the neurons in this region when both estrogen and stress are present.

After removing the ovaries from all subjects and implanting half of the rats with estrogen, the researchers exposed them to ten days of either immobilization stress (two hours in a rodent immobilization bag) or home cage rest. They then sectioned the rats’ brains and examined the neurons in question.

“We used Neurolucida and Neurolucida Explorer to measure dendritic length and branch point number in a set of pyramidal neurons that had been filled with the fluorescent dye Lucifer Yellow,” said lead author Dr. Rebecca Shansky. “The software was very user-friendly, and we were easily able to customize the settings to get just the analyses we wanted,” Dr. Shansky added.

What they found was increased dendritic arborization and spine density in the females treated with estrogen, “indicating that estrogen and stress can interact at the level of this circuit to produce a unique response to stress in females,” according to the paper “Estrogen Promotes Stress Sensitivity in a Prefrontal Cortex–Amygdala Pathway,” published earlier this year in Cerebral Cortex.

Read the free abstract, or download the full paper at Cerebral Cortex.

Rebecca M. Shansky, Carine Hamo, Patrick R. Hof, Wendy Lou, Bruce S. McEwen, and John H. Morrison, “Estrogen Promotes Stress Sensitivity in a Prefrontal Cortex–Amygdala Pathway” (Cereb Cortex 2010; 20: 2560-2567)

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Brain Inflammation May Cause Autoimmune Disease Stress

When your mouth is dry, your joints are stiff, or your heart is inflamed because your immune system is attacking your own body, chances are you’re suffering from a little stress. A recent study shows that there may be physiological reasons why patients with autoimmune diseases experience increased levels of anxiety.

Scientists at the City University of New York Medical School, Columbia University, and the University of Messina suggest it may be brain inflammation that leads to elevated stress in patients with autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s syndrome.

After modeling these diseases in a population of mice by introducing cytokine B-cell activating factor (BAFF), the research group examined their emotional behavior. They also checked for brain inflammation, stress-induced c-Fos protein, and the proliferation of progenitor cells in the hippocampus, using Neurolucida Explorer.

They found that the older mice produced anxiety-like characteristics associated with brain inflammation. These anxious mice responded to mild stress-inducing stimuli by displaying abnormal activity within the limbic system — the region of the brain that controls basic emotions.

During the course of the study, Neurolucida Explorer was used to calculate dendritic length. “I was very pleased with Neurolucida Explorer,” said Dr. Fortunato Battaglia. “I find the software very friendly and the quantitative data were crucial for our work. I am looking forward to using it again in future experiments.”

Read the free abstract or download the complete paper “Reduced Adult Neurogenesis and Altered Emotional Behaviors in Autoimmune-Prone B-Cell Activating Factor Transgenic Mice” at Biological Psychiatry.

Rosalia Crupi, Marco Cambiaghi, Linda Spatz, Rene Hen, Mitchell Thorn, Eitan Friedman, Giuseppe Vita, Fortunato Battaglia, “Reduced Adult Neurogenesis and Altered Emotional Behaviors in Autoimmune-Prone B-Cell Activating Factor Transgenic Mice” (Biological Psychiatry (2010) 67 6, 558-566)

{Illustration of a human brain and skull licensed under the Creative Commons Attribution 2.5 Generic license}

Multiple Sclerosis and Schizophrenia Research May Benefit From New Findings

Myelin, which insulates axons in the central nervous system is produced by oligodendrocytes. But not all oligodendrocytes are equal.

Led by Dr. Jonathan Vinet of the Université Laval in Quebec, scientists have identified three different types of oligodendrocytes in the mouse hippocampus: “ramified,” “stellar,” and “smooth.”

Each type displayed varying morphological characteristics, mainly in shape, volume, and branching behavior, which led the researchers to believe that the three types represent different stages of maturation.

As described in the paper, “Subclasses of oligodendrocytes populate the mouse hippocampus,” published in the European Journal of Neuroscience, the “smooth,” or most simple type possibly morphs into the “stellar,” which eventually develops into the most complex of the three, the “ramified” oligodendrocyte.

The identification of these morphologically distinct oligodendrocyte populations in the hippocampus may help researchers determine which specific types of oligodendrocytes are affected in diseases such as schizophrenia and multiple sclerosis.

Using a Neurolucida system with an Olympus AX-50 microscope, the scientists formed 3D reconstructions of the hippocampal oligodendrocytes integral to their study. They then analyzed their tracings with Neurolucida Explorer.

“Without Neurolucida we couldn’t have carried out this study,” said Dr. Attila Sik, “it was an essential component. Nice piece of equipment, for sure.”

Read the free abstract, or access the full article (by subscription), at the European Journal of Neuroscience.

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University of Maryland Scientists Reconstruct Neuronal Processes in 3D with Neurolucida

University of Maryland School of Medicine researchers have used Neurolucida since it was in its embryonic stages in the 1960s. Now, nearly a half-century later, the Department of Anatomy and Neurobiology continues using Neurolucida in their research, as outlined in a recent study concerning the organization of the olfactory system.

Dr. Michael Shipley and his team collaborated with scientists from Hungary and Japan on the paper “Molecular Identity of Periglomerular and Short Axon Cells,” published in the January 20 issue of The Journal of Neuroscience. The study involved the examination of the olfactory systems—including the olfactory sensory axons and juxtaglomerular neurons— of TH transgenic mice expressing green fluorescent protein.

“Neurolucida was essential for the tracing and derivation of basic morphometric parameters (length, etc.),” said co-author Dr. Adam C. Puche. The research team used Neurolucida to create 3D reconstructions of interglomerular connections, a process which aided in the determination that “different JG cell chemotypes contribute to distinct microcircuits within or between glomeruli.”

Access the article abstract and full text (by subscription) at

{Image courtesy of Adam C. Puche, Ph.D., University of Maryland, School of Medicine}

Emi Kiyokage, Yu-Zhen Pan, Zuoyi Shao, Kazuto Kobayashi, Gabor Szabo, Yuchio Yanagawa, Kunihiko Obata, Hideyuki Okano, Kazunori Toida, Adam C. Puche, and Michael T. Shipley (2010), “Molecular Identity of Periglomerular and Short Axon Cells” The Journal of Neuroscience, 30(3):1185-1196

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Neurolucida Helps Scientists Better Understand Sound Localization

Birds and mammals hear binaurally, hearing sounds through two ears. Binaural hearing allows them to determine which direction a sound came from—a pivotal element of survival.

Doctors Armin H. Seidl, Edwin W. Rubel, and David M. Harris of Seattle’s Virginia Merrill Bloedel Hearing Research Center at the University of Washington recently published a study in the Journal of Neuroscience that may encourage scientists to think in new ways about the sound localization process.

The research involved the sectioning and 3D reconstruction of the brains and brainstems of over 50 white leghorn chickens.  By analyzing the part of the brain responsible for computing the interaural time difference (ITD)—the difference in the arrival time of a sound between two ears—the scientists determined that the length of the axons in the chicken sound localization circuit alone cannot compensate for external ITDs, as previously thought. Instead, it seems that the axon diameter and the distances between Nodes of Ranvier are also vital to the process.

Dr. Seidl explained that his team used Neurolucida in the study for two reasons:

“Neurolucida allowed us to trace and reconstruct labeled axon over several 3D images. Hence, we could record labeled axons at high magnification and stitch them together over several Z-stacks of images. Pivotal was also the possibility of introducing branch points to the 3D trace.”

“Neurolocida Explorer allowed us to measure the reconstructed axon and to measure specific segments, i.e., from a certain branch point or to a certain ending.”

“We found Neurolucida very user friendly and we always got great help from your online support department. We are planning on using it in future,” Seidl said.

Read “Mechanisms for Adjusting Interaural Time Differences to Achieve Binaural Coincidence Detection” at The Journal of Neuroscience Online.

{Image: Nuclei outlined with the contour function in Neurolucida. Courtesy of Dr. Armin Seidl}

Armin H. Seidl, Edwin W. Rubel, and David M. Harris (2010), “Mechanisms for Adjusting Interaural Time Differences to Achieve Binaural Coincidence Detection.” Journal of Neuroscience, 30(1):70-80