Mutations in a TRP ion channel cause dopaminergic cell loss in C. elegans

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Tracking C. elegans with WormLab

Researchers have identified two strains of mutant C. elegans that lose the majority of their dopaminergic neurons in adulthood, a characteristic of neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease.

The two strains of mutant C. elegans (ot337 and ot477) showed normal development of dopaminergic neurons, however these neurons began to progressively decline in adulthood; and the deterioration was not an occurrence of the normal aging process, the authors say in their paper published in the Journal of Neuroscience.

After mapping the worms’ entire genome sequence, the researchers pinpointed the site of the mutation – the Transient Receptor Potential (TRP) mechanosensory channel trp-4 – a mutation that has not previously been implicated in dopaminergic neuron death.

“We describe here a novel Caenorhabditis elegans mutant with robust and progressive degeneration of dopaminergic neurons during postembryonic development,” the authors say in their paper. “We show that a single amino acid substitution in a TRP channel is responsible for the phenotype, implicating mutations in TRP family channels as a direct cause of dopaminergic degeneration for the first time.”

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Scientists Map Photoreceptor Cells of Deep-Sea Sharks

Topographic mapping of photoreceptor cells. a Scleral eyecup with the retina uppermost, where peripheral slits have been made to allow flattening. The retina is then carefully removed from the sclera, freed of the underlying choroidal tapetum lucidum and wholemounted onto a non-subbed slide. Scale bar = 1 cm. b Screen shot taken from Stereo Investigator showing the green inclusion line and the red exclusion line overlaid on the rod photoreceptor array, viewed here on the axial plane. Colors are visible online only. Scale bar = 10 μm. c Optic nerve head as seen under a light microscope. Note the fascicles or bundles of ganglion cell axons converging on the optic nerve head. Scale bar = 200 μm.

a. Topographic mapping of photoreceptor cells. a Scleral eyecup with the retina uppermost, where peripheral slits have been made to allow flattening. The retina is then carefully removed from the sclera, freed of the underlying choroidal tapetum lucidum and wholemounted onto a non-subbed slide. Scale bar = 1 cm. b. Screen shot taken from Stereo Investigator showing the green inclusion line and the red exclusion line overlaid on the rod photoreceptor array, viewed here on the axial plane. Colors are visible online only. Scale bar = 10 μm. c. Optic nerve head as seen under a light microscope. Note the fascicles or bundles of ganglion cell axons converging on the optic nerve head. Scale bar = 200 μm.

The deepest parts of the ocean are dark. For marine animals living one thousand feet below sea level and lower, the absence of light makes it challenging to find food, attract a mate, and identify predators.

Some animals make their own light through a process called bioluminescence. Others have adapted in ways that help them detect light in an environment beyond the reach of the sun’s rays.

In the first stereological study of the eyes of deep sea sharks, scientists in Queensland, Australia quantified photoreceptor cell populations and mapped their topography in the retina of five different species of deep sea sharks.

The sharks, including the Borneo catshark, the longsnout dogfish, the prickly dogfish, the beige catshark, and McMillan’s catshark, were caught in the nets of deep-sea fishermen off the coast of New Zealand. Each type of shark featured large, round pupils and a tapetum lucidum, a reflective structure at the back of the eye – two common adaptations deep-sea animals use to enhance sensitivity in environments where bioluminescence is the only available light source, according to the paper.

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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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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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Researchers Restore Neuron Branching in Model of Mutant NHE6 Gene

Mice with the  NHE6 gene mutation show less dendritic branching. Using Neurolucida, researchers traced a GFP-labeled neuron reconstructed with confocal z stacks in a wild type mouse (left) and a mouse with a mutant NHE6 gene (right).

Mice with the NHE6 gene mutation show less dendritic branching. Using Neurolucida, researchers traced a GFP-labeled neuron reconstructed with confocal z stacks in a wild type mouse (left) and a mouse with a mutant NHE6 gene (right). Image courtesy of first author Qing Ouyang, PhD, Alpert Medical School, Brown University.

Children with the neurogenetic disorder Christianson Syndrome experience delays in language and learning; they may also have seizures, and display symptoms of autism. Scientists say these disorders are a result of stunted brain cell growth, which occurs because of a mutation in the gene that produces the protein NHE6—a protein also mutant in several forms of autism.

Neurons in human brains with the mutant gene don’t branch as robustly or form connections as well as neurons in normal brains. But researchers at Brown University may have found a way to restore the ability of these cells to grow properly.

In their study, published in the journal Neuron, senior author Dr. Eric Morrow and his team describe a signaling pathway for neuronal growth involving NHE6. Using a mouse model with an NHE6 gene mutation, they found that reduced levels of NHE6 combined with increased acidity in a cell’s endosome, results in a depletion of the receptor protein TrkB, a key player in the growth and branching of axons and dendrites.

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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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Researchers from Quebec Delay Symptoms of Huntington’s Disease in Mouse Model

Neuron_with_mHtt_inclusionA montage of three images of single striatal neurons transfected with a disease-associated version of huntingtin, the protein that causes Huntington’s disease; By: Dr. Steven Finkbeiner, Gladstone Institute of Neurological Disease, The Taube-Koret Center for Huntington’s Disease Research, and the University of California San Francisco; licensed under the Creative Commons Attribution 3.0 Unported license.

Patients with Huntington’s disease deteriorate physically, cognitively, and emotionally. There is no cure for the inherited illness, but scientists may have found a way to slow down the onset of symptoms. Researchers in Quebec increased the expression of a molecule known as pre-enkephalin (pENK) in a mouse model of Huntington’s disease (HD) and saw promising results.

Since reduced expression of pENK is a hallmark of the disease, and neurons containing this molecule are some of the first cells to die in the brains of HD patients, the researchers hypothesized that an HD brain over-expressing pENK might have beneficial results. Their study offers the first evidence that increased pENK expression leads to a delay in muscle dysfunction, improved motor activity, memory, and lower anxiety in early-onset HD. Continue reading “Researchers from Quebec Delay Symptoms of Huntington’s Disease in Mouse Model” »

Researchers use WormLab to reveal that nicotine addiction is heritable in C. elegans

Interacting Worms

Smokers aren’t only hurting themselves, they’re also hurting their children and grandchildren. So says a study published last month in the EXCLI Journal.

Scientists at East Carolina University, in Greenville, North Carolina saw unusual behavior in C. elegans roundworms exposed to nicotine at an early stage of development. But that’s not all – the researchers also witnessed abnormal behavior and withdrawal symptoms in subsequent generations of worms even though these groups were not directly exposed to nicotine. Continue reading “Researchers use WormLab to reveal that nicotine addiction is heritable in C. elegans” »

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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