Hippocampal Neurons Change After Melatonin Injection

Representative dendrites of dentate gyrus neurons of Siberian hamsters injected with melatonin (stained with Cresyl violet). Ikeno et al found hamsters injected with melatonin displayed decreased spine density on neurons in the dentate gyrus.

Representative dendrites of dentate gyrus neurons of Siberian hamsters injected with melatonin (stained with Cresyl violet). Ikeno et al found hamsters injected with melatonin displayed decreased spine density on neurons in the dentate gyrus. Image courtesy of Tomoko Ikeno, Ph.D.

Night falls and a powerful hormone called melatonin kicks in. The gears of the circadian clock are turning as you get ready for bed and soon drift off to dreamland. But all is not quiet in the brain. In response to the circadian rhythm, neurons are transforming.

A new study published in the journal Hippocampus found that melatonin prompts dendrites to grow longer in one part of the brain, while in another part the hormone causes dendritic spine loss.

In their study, scientists at Ohio State University injected Siberian hamsters with a dose of melatonin in the afternoon, several hours before a natural increase in the hormone would normally occur. Four hours after the injection, they used Neurolucida to examine sections of their brains, reconstructing neurons in two areas of the hippocampus – the CA1 and dentate gyrus. They then used the software to calculate the number of branch points and length of dendrites in their reconstructions. What they saw was longer, more complex dendrites in the CA1 region of the hippocampus of hamsters that received melatonin versus those that received a placebo. Then they analyzed spine density, finding that hamsters that received melatonin had decreased spine density in the dentate gyrus than the control group.

“By using Neurolucida, we found that melatonin treatment induced rapid remodeling of hippocampal neurons and induced a nighttime state of the hippocampal neuronal morphology,” said Dr. Tomoko Ikeno, who worked with Dr. Randy Nelson on the study.

The “nighttime state” she refers to is characterized by the presence of certain hormones produced during the dark hours of night. In their analysis, the researchers saw elevated levels of Period1 and Bmal1 after melatonin injection. These hormones are expressed by genes associated with the circadian clock, and their presence offers evidence that “melatonin functions as a nighttime signal to coordinate the diurnal rhythm” and that this rhythm compels hippocampal neurons to change structurally, according to the paper.

Ikeno, T. and Nelson, R. J. (2014), Acute melatonin treatment alters dendritic morphology and circadian clock gene expression in the hippocampus of Siberian Hamsters. Hippocampus. doi: 10.1002/hipo.22358

 

How Transplanted Stem Cells Behave in Injured Spinal Cord Tissue

A representative confocal image of spinal cord tissue fluorescently immunolabeled for SC121 in conjunction with GFAP – markers that allowed the researchers to track stem cell differentiation and migration by stereological quantification. (Image provided by study author Dr. Aileen J. Anderson)

A representative confocal image of spinal cord tissue fluorescently immunolabeled for SC121 (red) in conjunction with GFAP (green) – markers that allowed researchers to quantify stem cell differentiation and migration. (Image provided by study author Dr. Aileen J. Anderson)

Research has shown that transplanting human neural stem cells into damaged spinal cords restores locomotor function in a mouse model of spinal cord injury1. Researchers who worked on that study have published another paper examining how these neural stem cells behave in injured tissue as they aid in healing. Learning how stem cells behave in injured tissue will hopefully help researchers develop better treatments for spinal cord injuries.

In the study, researchers used Stereo Investigator to stereologically quantify the survival, migration, proliferation, and differentiation of human neural stem cells transplanted into injured and uninjured mice. Stem cells were analyzed in mouse brain tissue specimens 1, 7, 14, 28, and 98 days after transplantation. The research found that there were fewer stem cells in the injured animals compared to the uninjured animals at all time points, stem cells in injured mice localized near the center of the injury, a delay of stem cell proliferation in injured tissue led to an overall deficit of actively dividing cells, proliferation in injured mice occurred closer to the injection sites (the locations where the stem cells were injected into the mice), and the injured microenvironment increased differentiation to more mature oligodendrocytes.

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Dendritic Spine Loss Reported in Schizophrenia and Bipolar Disorder

Golgi-stained human brain tissue from the dorsolateral prefrontal cortex.

Golgi-stained human brain tissue from the dorsolateral prefrontal cortex.

Schizophrenia and bipolar disorder are very different mental illnesses, but researchers are discovering evidence that the two disorders have some common pathologies. According to a recent study, a shared characteristic appears to be dendritic spine loss.

The researchers used Neurolucida to study pyramidal cells in human brain tissue from individuals with schizophrenia (n=14), individuals with bipolar disorder (n=9) and unaffected control participants (n=19). The pyramidal cells were located in the dorsolateral prefrontal cortex – a region that plays a key role in working memory. Bipolar patients showed significantly reduced spine density (10.5 percent) compared to control. Schizophrenic patients also showed lower spine density (6.5 percent), but this number just missed significance when compared to control patients. Individuals with both illnesses showed a lower number of spines per dendrite, as well as reduced dendritic length compared to controls.

To obtain these results, researchers analyzed 15 Golgi-stained pyramidal cells in each tissue sample. They used Neurolucida to reconstruct the longest dendrite on the pyramidal cells and to mark spines. After the researchers finished reconstructing the cells, Neurolucida provided them with important data about the dendrites and spines.

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Two 2014 Nobel Prize Laureates Used Neurolucida in their Groundbreaking Research

May-Britt and Edvard Moser

Drs. May-Britt and Edvard Moser Image from GEIR MOGEN / NTNU

Drs. May-Britt and Edvard Moser were awarded the 2014 Nobel Prize in Physiology or Medicine for discovering the cells that form a network for spatial navigation in the brain, and we’re proud to say they are MBF Bioscience customers and used Neurolucida in their research.

In 2006, the Norwegian husband and wife team published a paper in the journal Science entitled “Conjunctive Representation of Position, Direction, and Velocity in Entorhinal Cortex” – a pivotal step in a line of research initiated in 1971 by co-laureate Dr. John O’Keefe (The Hippocampus as a Spatial Map). In their study, the scientists used Neurolucida to create 3D reconstructions of a complex network of neurons that make it possible for rats, and other animals, including humans, to navigate the world around them.

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Anorexia Accelerates the Development of the Rat Hippocampus

spine_edited

This image stack was used in the study to analyze spine density. Image courtesy of Tara Chowdhury, Ph.D. first author of the study.

To find out how anorexia nervosa changes the brain, scientists at New York University are studying a rat model of the disease called activity-based anorexia (ABA). Previously, they discovered that ABA rats develop unusually robust dendritic branching of neurons in part of the hippocampus. Their new study takes those findings a step further, illuminating more differences between the brains of healthy versus ABA rats, and offering evidence that ABA rats may be developing too early, closing a critical period of development too soon.

But before making any conclusions about ABA brains, the researchers made some interesting discoveries about normal brain development. Using Neurolucida to analyze CA1 pyramidal cells in the stratum radiatum layer of the ventral hippocampus, they found that after puberty, around postnatal day 51, dendrites go through a growth spurt, more than doubling the number of branches seen seven days earlier. This growth spurt is followed by a decrease, or a pruning, which the researchers say is part of the normal maturation process.

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Scientists Use Neurolucida to Create 3D Reconstructions of Placental Villous Trees

(a,b) Comparison of the microscopic aspects of a thin (4–6 μm) histological section of a human placenta after staining with hematoxylin/eosin (a) with the microscopic aspects of a whole-mount isolated villous tree after staining with hematoxylin (b). The scale bars in a and b are 250 μm. (a) Various cross- and longitudinal sections of villi can be recognized. The stromal architecture inside the sectioned villi is visible. The cross-sections of branches belong to an unknown number of villous trees. (b) A single villous tree is visible, and branches are not sectioned. The hierarchical positions of nodes (branching points) and the branching topology can be recognized.

(a,b) Comparison of the microscopic aspects of a thin (4–6 μm) histological section of a human placenta after staining with hematoxylin/eosin.

When neuroscientists started studying neurons in 3D, it revolutionized brain science. Now, for the first time, scientists are using this same technology to study the human placenta, and they’ve made some fascinating new discoveries about its structure.

Using Neurolucida to create 3D reconstructions of villous trees – three-dimensional structures in the placenta that facilitate gas and nutrient exchange between the fetus and mother – researchers in Munich, Germany uncovered a wealth of information about their architecture.

For the first time, they analyzed the complexity of villous tree branches and branching, determined the number and location of nodes (branching points), and measured branch angles, discovering a surprising correlation between the branching angle of terminal branchesand the fetoplacental weight ratio (BW/PW) – a calculation commonly used to measure fetal health in prenatal medicine.

“The results show that 3D analysis with Neurolucida reaches beyond the horizons of 2D histology, the current gold standard in placenta morphology/pathology,” said Dr. Hans-Georg Frank, an author of the study. Continue reading “Scientists Use Neurolucida to Create 3D Reconstructions of Placental Villous Trees” »

Delayed loss of neurons occurs in mice with mild TBI and anxiety

Almeida-Suhett et al saw delayed loss of GABAergic interneurons in the BLA within the first week after mild CCI. (Representative photomicrographs of GAD-67 immunohistochemically stained GABAergic interneurons in the BLA of sham (left), 1-day CCI (middle), and 7-day CCI (right) animals. Total magnification is 630x; scale bar, 50 µm.)

Almeida-Suhett et al saw delayed loss of GABAergic interneurons in the BLA within the first week after mild CCI. (Representative photomicrographs of GAD-67 immunohistochemically stained GABAergic interneurons in the BLA of sham (left), 1-day CCI (middle), and 7-day CCI (right) animals. Total magnification is 630x; scale bar, 50 µm.)

Soldiers, athletes, and other individuals who suffer a traumatic brain injury often develop anxiety disorders, but scientists aren’t sure why. Some speculate that fear about future health or the stress of the trauma itself contributes to elevated anxiety, while others suspect changes happening inside the brain as a result of the injury are to blame.

Researchers at Maria Braga’s lab at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, recently found direct evidence that physical changes happen in the brain after TBI that coincide with increased anxiety levels.

She and her team studied a rat model of mild TBI, focusing on the basolateral amygdala (BLA) – a brain region often damaged by TBI, which has also been associated with increased fear and anxiety in instances of hyperactivity.

To find out what happens in the BLA that might be causing anxiety after a mild TBI, the researchers analyzed changes in synaptic activity in this region. Using Stereo Investigator with the optical fractionator probe to perform a stereological quantification of Nissl-stained and GAD-67 immunostained brain cells, they found that many of the inhibitory neurons – the cells that quiet activity – were lost seven days after injury. Whole cell recordings from principal neurons confirmed that the inhibitory cells’ synaptic transmissions were impaired during this period, resulting in increased excitability and “open field tests” showed elevated anxiety levels in post-injury rats at the exact same time point. Continue reading “Delayed loss of neurons occurs in mice with mild TBI and anxiety” »

Higher levels of pTau found in Alzheimer’s disease patients with psychosis

murray_ptau

An image of neurofibrillary tangles and neuropil threads

People with Alzheimer’s disease suffer from severe memory loss and often have problems focusing, reasoning, and communicating. About half of all Alzheimer’s patients also experience delusions and hallucinations, this is called Alzheimer’s disease with psychosis, and scientists at the University of Pittsburgh are learning more about this severe version of the disease.

In a recent study, researchers at Dr. Robert Sweet’s lab zeroed in on a protein called tau, which forms tangles in the brains of Alzheimer’s patients, and along with amyloid plaques is one of the major hallmarks of the disease. But despite being involved in these pathological conditions, tau and amyloid may instigate other processes as well – namely, synaptic toxicity, which the authors say is “the strongest correlate of cognitive decline in Alzheimer’s disease.”

Recent research suggests that amyloids (misfolded proteins) drive the deterioration of synapses, but phospho-tau (tau, which has undergone phosphorylation), enables the process. So in their study the Pittsburgh research team analyzed the presence of tau in the prefrontal cortex, a region of the brain involved in higher processes, of 45 Alzheimer’s disease patients with and without psychosis.

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New Neurons Erase Memories

Dentate gyrus

Neurogenesis occurs in the dentate gyrus, pictured here, from birth through adulthood.

A baby laughs at an elephant at the zoo. A toddler runs across a beach. Small children make memories all the time, but how many will they recall as the years pass? Maybe none at all. The phenomenon is called “infantile amnesia,” and scientists may have pinpointed a reason for why it occurs – neurogenesis.

Researchers at the Hospital for Sick Children in Toronto say that when new brain cells integrate into existing circuitry, they remodel the structure of networks already in place, wiping out the information previously stored there. This process is prevalent in infancy and early childhood because this is the time when new brain cells are being generated faster and more frequently than at any other time in a human being’s life. Humans and other mammals spawn new neurons throughout their lifespans, although the rate of neurogenesis decreases significantly with age.

In their paper, published in Science, the researchers explain how recent studies have focused on how new brain cells can lead to new memories, but the Toronto team speculated that neurogenesis could also wipe away memories. To test their hypothesis, they conducted a series of studies on populations of newborn and adult mice. Neuron development in mice occurs in much the same way as in humans, with rapid cell genesis in infancy that tapers off with age.

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Scientists Use Stereo Investigator in Spinal Cord Injury Study

Stereo Investigator Graphic

After an initial spinal cord injury, a cascading series of secondary events continues to do damage to the nervous system. One particularly damaging event is the death of oligodendrocytes—neuroglial cells that help protect and support the central nervous system. Scientists are learning more about the mechanisms involved in this process in the hope that their research may lead to the development of new therapeutic treatments for stopping some of the secondary damage before it occurs.

Researchers at the Miami Project to Cure Paralysis previously found that astrocytes play a role in oligodendrocyte death after spinal cord injury, but they weren’t quite sure how. Their new study identifies a culprit – an enzyme called NADPH oxidase. According to their paper, published in PLOS One, astrocytes activate NADPH oxidase within oligodendrocytes after an injury, triggering a toxic effect in the tiny neural cells.

In their study, the researchers set out to see what would happen if they could prevent post-trauma NADPH oxidase activation. Their results proved promising, with both in vitro and in vivo experiments resulting in lower oligodendrocyte death.

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