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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Anorexia Accelerates the Development of the Rat Hippocampus

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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” »

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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Brain Cleans Itself During Sleep; Scientists Image Cerebral Fluid Flow With Neurolucida

 

With some exceptions, humans and animals prefer to live in an environment free of filth. We clean our bodies and our homes so we can live healthy and productive lives. It turns out, the brain does too.

Researchers at the University of Rochester discovered that the brain cleans itself during sleep—explaining one of the major reasons we partake in a nightly ritual that has mystified scientists for centuries.

“Sleep has a critical function in ensuring metabolic homeostasis,” Dr. Maiken Nedergaard et al say in their paper published in Science. “The restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.”

Instead of a lymphatic system, the brain has what the researchers call a “glymphatic system.” Waste products that build up during waking hours flush out through the membranes of glial cells in the brain’s interstitial space as cerebral spinal fluid (CSF) flows in. In the process, proteins like b-amyloid, which are associated with Alzheimer’s disease, are washed away. The exchange of fluids occurs along the brain’s vasculature; CSF flows in around arteries, while interstitial fluid (ISF) exits in the space around veins.

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3D Reconstructions of Neurons Reveal More Branching in Sedentary Rats

Left: A neuron from the brain of a rat that exercised for two hours each day. Right: A neuron from the brain of a sedentary rat.

Left: A neuron from the brain of a rat that exercised for two hours each day.
Right: A neuron from the brain of a sedentary rat. Scientists saw greater branching in inactive versus active rats. (Image courtesy of Dr. Patrick Mueller)

Scientists discovered that inactivity makes brain cells grow, but not in a good way. In a study published in the Journal of Comparative Neurology, researchers found more neuronal branching in sedentary rats compared to active rats. The growth occurred in a region of the brain that controls blood pressure, leading the scientists to hypothesize that these changes may be part of the reason inactivity is linked to an increased risk of heart disease.

Using Neurolucida to reconstruct neurons in 3D, the scientists at Dr. Patrick Mueller’s lab at Wayne State University School of Medicine, in Detroit, saw structural differences between the brains of active and inactive rats.

Focusing on the rostral ventrolateral medulla (RVLM) – an area that controls several critical biological processes that rats as well as humans do unconsciously, like swallowing, breathing, and regulating blood pressure, the scientists saw longer dendrites, more dendritic branching, and more intersections with other neurons in sedentary rats.

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Neurons in the Basal Forebrain are Exquisitely Organized

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A micrograph of the nucleus basalis of Meynert, a group of neurons in the basal forebrain that produces most of the acetylcholine supplied to the cerebral cortex.
Image from Wikimedia Commons

The loss of cholinergic neurons is one of the earliest pathological events of Alzheimer’s disease. Cholinergic neurons in the basal forebrain supply the cerebral cortex with acetylcholine, an important neurotransmitter that plays a role in learning, memory, and attention. Details about the function and organization of basal forebrain (BF) neurons are not well understood, but Dr. Laszlo Zaborszky has recently uncovered new information about the structure of this complex area of the brain.

In a paper published in Cerebral Cortex, Dr. Zaborszky and his team report that they discovered exquisite organization in the basal forebrain of rats; the extent of overlap between basal forebrain neuronal populations correlates with the connectivity strength between their cortical targets. This means that basal forebrain neurons that overlap extensively project to frontal and posterior cortical areas that are strongly connected. Connectivity strength between cortical areas is defined by the number of neurons in a defined posterior cortical area that project to a defined area in the frontal cortex. Continue reading “Neurons in the Basal Forebrain are Exquisitely Organized” »

Scientists Discover Anorexia-Driven Changes to Dendrites With Neurolucida

A digital reconstruction of a CA1 pyramidal cell from the ventral hippocampus, traced using Neurolucida with Sholl spheres at 20 micron intervals. Cells in this region featured greater dendritic length and branching versus controls.

A digital reconstruction of a CA1 pyramidal cell from the ventral hippocampus of a rat with activity-based anorexia, traced using Neurolucida with Sholl spheres at 20 micron intervals. Cells in this region featured greater dendritic length and branching versus controls.

Gaunt facial features and a frighteningly thin figure are physical hallmarks of anorexia nervosa, an eating disorder that predominantly affects adolescent girls. But in addition to extreme weight loss, changes take place that aren’t as visually apparent. For the first time, scientists in New York have found evidence of brain plasticity in the activity-based anorexia (ABA) mouse model.

Led by Dr. Chiye Aoki of New York University, the research team used Neurolucida to analyze pyramidal neurons in the rat brain. Since anorexia is linked to elevated stress hormones and anxiety, the researchers focused on the hippocampus, a region that regulates anxiety and is known to change structurally in response to hormones and stress.

“Using Neurolucida, we were able to collect, store, and analyze large amounts of data with more precision and accuracy than would have been possible without the digital interface,” said Tara Chowdhury, a graduate student working in Dr. Aoki’s lab, and first author of the paper.

“Additionally, with its very approachable interface, the software allowed us to trace dendrites, get precise thickness measurements, and categorize spine types easily during tracing. The built-in Sholl analysis and spine analysis tools resulted in quick quantification of all the measurements that would have taken hours to achieve without Neurolucida.”

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Neurolucida Helps Scientists Discover that Gorillas are Relevant in the Study of Alzheimer’s Disease

Cortical neurons containing tau termed neurofibrillary tangle seen in the human brain with Alzheimer's disease. The researchers used Neurolucida to count and chart similar neurons in the gorilla brain. 

Cortical neurons containing tau, termed neurofibrillary tangle, seen in the human brain with Alzheimer’s disease. The researchers used Neurolucida to chart similar lesions in the gorilla brain.

Humans and gorillas are approximately 98% identical on a genetic level, however there is little published research exploring Alzheimer’s disease pathology in gorillas. A new paper reports that gorillas display similarities in advanced age to humans  ̶  including the presence of Alzheimer’s disease precursors like amyloid-beta (Aβ) plaques and tau lesions.

The study, published in the Journal of Comparative Neurology, provides evidence of Alzheimer’s disease precursors in the western lowland gorilla. Their findings broaden the scientific community’s understanding of the aging brain of some our closest living relatives and offer new insights for Alzheimer’s disease research.

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Ohio State Neuroscientists Use Neurolucida to Analyze Brain Cells in Sexually Active Hamsters

A Golgi stained human neocortical pyramidal neuron. Morris et al studied cells like this to determine the affect of sexual experience on the adult brain. Using Neurolucida, they saw shorter, less extensive dendrites in hamsters which mated during adolescence versus controls.

A Golgi-stained human neocortical pyramidal neuron. Morris et al. studied cells like this to determine the effect of sexual experience on the adult brain. Using Neurolucida, they saw shorter, less extensive dendrites in hamsters which mated during adolescence versus controls.

Scientists hypothesize that during puberty, experiences influence brain development in ways that shape brain structure and even behavior in adulthood. One type of experience that often arises in the minds of pubescent teens and adolescents is sex. But a study published in the journal Hormones and Behavior suggests engaging in sexual activity too soon could be detrimental to the adult brain, and may lead to depression.

In their study of Siberian hamsters, scientists at the Wexner Medical Center at Ohio State University say adolescent sexual experiences alter brain structure.

“We used Neurolucida to reconstruct the morphology of prefrontal cortical neurons in the brains of Siberian hamsters that were exposed to sexual experience during early adolescence, later in young adulthood, or left socially isolated,” said Dr. Zachary M. Weil, an author of the study. “Interestingly, hamsters that engaged in sexual experience during early adolescence but not during other developmental periods exhibited reduced branching and dendritic length in the prefrontal cortex.”

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