Humans Generate Most Cerebellar Granule Cells Postnatally

Human cerebellum section with silver stain

Human cerebellum section with silver staining. Image from the Iowa Virtual Slidebox

The human brain undergoes extraordinary development in utero, with major growth continuing throughout childhood, especially during the first year. Scientists know a lot about how the neurons and circuits of the human brain develop in infancy, but a lack of specific knowledge about key elements has left doctors mystified by certain childhood disorders like SIDS and autism.

Neuroscientists at Ludwig-Maximillians-University of Munich have made new revelations about the development of cerebellar granule neurons. The smallest and most numerous type of neuron in the human brain, these cells transmit motor and sensory information to Purkinje cells, large neurons that are said to play a role in coordinating motor movement and are the sole source of output for the cerebellar cortex.

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Exercise Heals the Brain After Binge Drinking

The granule cell layer of the dentate gyrus captured using a 100x objective. Image provided by Mark Maynard.

The granule cell layer of the dentate gyrus. Image provided by Mark Maynard.

Binge drinking damages brain regions responsible for memory, decision-making, and behavioral control. After a binge, the brain begins to heal itself but not much is known about this self-repair process. In a study published in PLoS ONE, researchers used rats to find that binge drinking damages the hippocampus, and exercise reverses this damage.

The study found that excessive ethanol killed granule neurons in the dentate gyrus (DG), a part of the hippocampus, and significantly decreased the volume of the DG. Rats that exercised after binging had more DG granule neurons and a larger DG than rats that did not exercise after a binge. In fact, rats that exercised after binging had a similar number of DG neurons and a similar DG volume to that of controls, indicating that exercise almost fully reversed damaged to the DG caused by binge drinking.

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Scientists use Stereo Investigator to Discover that Part of the Hippocampus Shrinks in Socially Isolated Rodents

Scientists studied cresyl-violet stained sections of the left brain hemispheres of isolated and group-housed rodents.

Scientists studied cresyl-violet stained sections of the left brain hemispheres of isolated and group-housed rodents. Image courtesy of the Venero Lab at The National University of Distance Education in Madrid, Spain.

Social isolation is stressful. Scientists have known it for decades. They also know that isolation causes changes to occur in the brains of rodents and primates. But most studies examine the effects of isolation during childhood; and the ones that do focus on adulthood tend to use male subjects. For the first time, researchers in Spain show that long-term social isolation causes part of the brain to shrink in the adult female degu, a highly social rat-like animal native to South America.

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Hawaii Scientists Measure Density of Parvalbumin-Interneurons With Stereo Investigator

Reduced density of PV-interneurons in Sepp1-/- mice. (A) Representative images showing PV expression in the hippocampus (left column) and inferior colliculus (middle and right columns) of WT Sepp1+/+ (top row) and Sepp1-/- (bottom row) mice. Higher magnification images of the inferior colliculus (far right) (B), Mean density of PV-interneurons per mm3 (+-SEM, n=6 per genotype) in brain regions investigated: SC; MS; DG, CA1, and CA2/3 of the hippocampus; IC. * P<0.01. Figure courtesy of Matthew W. Pitts, Ph.D.

Reduced density of PV-interneurons in Sepp1-/- mice. (A) Representative images showing PV expression in the hippocampus (left column) and inferior colliculus (middle and right columns) of WT Sepp1+/+ (top row) and Sepp1-/- (bottom row) mice. Higher magnification images of the inferior colliculus (far right) (B), Mean density of PV-interneurons per mm3 (+-SEM, n=6 per genotype) in brain regions investigated: SC; MS; DG, CA1, and CA2/3 of the hippocampus; IC. * P<0.01. Figure courtesy of Matthew W. Pitts, Ph.D.

Foods like tuna fish and Brazil nuts are rich in selenium, a mineral that scientists say has antioxidant effects, keeping the brain healthy and free of clutter so cells can work smoothly together. A key element of this process is Selenoprotein P (Sepp1) – a protein that delivers selenium to neurons by binding with another protein – ApoER2. Neuroscientists at the University of Hawaii say Sepp1 plays a critical role in brain function, and deficits may play a part in mental illnesses like schizophrenia.

In their study published in Neuroscience, the researchers investigate the relationship between Sepp1 and parvalbumin (PV)-interneurons – a class of brain cell that controls firing rates and synchronizes spiking activity among other groups of neurons. Previous research shows that these cells need selenium to develop properly, so the scientists set out to find out what affect a Sepp1 deficit would have on the mouse brain.

Led by Dr. Matthew W. Pitts, the research team compared the brains of wild type mice with Sepp1 deficient mice. They used a Zeiss Axioskop microscope equipped with Stereo Investigator to conduct a stereological analysis of PV-interneurons in several different regions of the mouse brain. Using Stereo Investigator’s optical fractionator probe, they observed reduced numbers of PV-interneurons along with elevated oxidative stress in the inferior colliculus of Sepp1 deficient mice, a region involved in processing auditory information.

“Stereo Investigator was particularly useful for estimating cell density in larger brain structures, such as the inferior colliculus,” said Dr. Pitts.

Since scientists speculate that dysfunctional PV-interneuron networks may be involved in neuropsychiatric conditions, the researchers conducted behavioral tests that showed impairments in contextual fear extinction, latent inhibition, and sensorimotor gating in the Sepp1 deficient mice – behaviors observed in some mental illnesses.

“Previous studies (Valentine et al., 2008) and our findings together indicate that ApoER2- mediated uptake of Sepp1 serves an important neuroprotective role in the inferior colliculus,” the authors say in their paper. “These findings may have relevance to neuropsychiatric conditions in which dysfunc- tional PV-interneuron networks have been implicated, such as epilepsy and schizophrenia.”

Pitts M.W., Raman A.V., Hashimoto A.C., Todorovic C., Nichols R.A., Berry M.J. Deletion of selenoprotein P results in impaired function of parvalbumin interneurons and alterations in fear learning and sensorimotor gating. Neuroscience. 2012 Apr 19;208:58-68. doi: 10.1016/j.neuroscience.2012.02.017.

 

New Zealand Scientists Use Stereo Investigator to Develop a New Model for Human Extreme Prematurity

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Oligodendrocytes, pictured here with a green fluorescent protein, form a myelin sheath – the insulation around axons. The extremely premature brain features a lower number of pre-oligodendrocytes, thereby decreasing myelination, a characteristic which has been associated with ADHD. Image courtesy of Wikimedia Commons.

Each year, nearly ninety thousand children are born extremely premature in the United States – that is, before 28 weeks gestation. Most of them survive, but about half the survivors suffer from severe health problems throughout their childhood and into adulthood, including learning and behavioral disorders such as ADHD.

“Treatment options are clearly urgently required to prevent the brain damage and associated memory deficits that follow extremely premature birth,” say the authors of a study published last month in the Journal of Neuroscience.

Treatment options are limited, the authors say, because current small animal models fall short in their mimicry of the extremely premature human brain. However, the researchers from the University of Otago in New Zealand have come up with a new animal model for human extreme prematurity, which they say more closely resembles the pathological and behavioral deficits seen among this population.

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Scientists Assess Kidney Damage with Stereo Investigator, Determine Ultrasound Prevents Organ Injury

Using the virtual tissue function of Stereo Investigator a series of photos of each section was captured using the 5X objective and automatically stitched together to form a montage of the entire section of kidney that clearly represents the degree of injury.  Kidneys are from mice treated either with vehicle (0.3 M sodium bicarbonate) or a single injection of folic acid (250 mg/kg, ip) in sodium bicarbonate, and mice were euthanized after 14 days. Injection of folic acid has been used as one model of chronic kidney disease. The degree of fibrosis in the kidney, revealed here by Masson’s trichrome stain (blue: collagen deposition), was determined using the area fraction fractionator probe in Stereo Investigator.

Using the Virtual Tissue module with Stereo Investigator, a series of photos of each kidney section was captured using the 5X objective and then automatically stitched together to form a montage of the entire section of kidney that clearly represents the degree of injury.  Kidneys are from mice treated either with vehicle (0.3 M sodium bicarbonate) or a single injection of folic acid (250 mg/kg, ip) in sodium bicarbonate. The mice were euthanized after 14 days. Injection of folic acid has been used as one model of chronic kidney disease. The degree of fibrosis in the kidney, revealed here by Masson’s trichrome stain (blue: collagen deposition), was determined using the area fraction fractionator probe in Stereo Investigator.

When it comes to health, kidneys are critical. From regulating blood composition to maintaining calcium levels, the pair of bean-shaped organs perform several essential tasks. Needless to say, interruption to kidney function can be disastrous.

Working with scientists in South Korea, researchers at the University of Virginia found a surprisingly simple treatment for renal ischemia-reperfusion injury (IRI) in mice, which is a model of acute kidney injury (AKI) in humans.

The researchers found that mice exposed to ultrasound prior to IRI “had preserved kidney structure and function accompanied by a reduction in tissue inflammation,” they report in their paper published this month in the Journal of the American Society of Nephrology.

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Scientists in Portugal Use Neurolucida Explorer to Analyze Neuroplasticity in Depression

Nucleus Accumbens

Nucleus Accumbens

Life’s little pleasures often elude those suffering from depression, including rats, who show little interest in sugar water after experiencing stress. This behavior leads scientists to speculate that the illness might be characterized by a defect in the brain’s neural reward circuit.

Recent research focuses on a key element of this circuit – the nucleus accumbens (NAc), part of the brain region known as the ventral striatum, which is thought to regulate motivation and reward processing. In a new study of stress-induced depression in rats, researchers at the University of Minho in Braga, Portugal saw morphological changes in the dendrites of medium spiny neurons in the NAc, alongside disturbances in gene expression in this region. They also saw these changes reversed after administering antidepressants.

By using Neurolucida Explorer to analyze 3D reconstructions of medium spiny neurons generated with Neurolucida, the researchers observed longer than normal dendrites and greater spine density in the depressed rats. According to the paper, these findings contrast with studies of the hippocampus and prefrontal cortex, where chronic stress leads to shorter dendrites.

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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.

Munich Scientists Analyze Placenta Morphometry with Stereo Investigator

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The placenta delivers nutrients from a mother’s blood to a developing fetus. It also produces hormones that help the baby grow during its forty or so weeks in utero. But the placenta’s powerhouse abilities don’t end there. The organ provides a wealth of information about the infant’s future health, allowing doctors to make predictions about whether or not the child will develop autism or, later in life, heart disease.

A recent study conducted at the Ludwig-Maximilians-University in Munich, Germany offers new insights into the relationship between the placenta and postnatal health.

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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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