Update on SIV remission studies

Recently presented insights on how an antibody used to treat intestinal diseases can suppress Read more

Granulins treasure not trash - potential FTD treatment strategy

Granulins are of interest to neuroscientists because mutations in the granulin gene cause frontotemporal dementia (FTD). However, the functions of granulins were previously Read more

Blood vessels and cardiac muscle cells off the shelf

How to steer induced pluripotent stem cells into becoming endothelial cells, which line blood Read more

Cancer

BAI1: a very multifunctional protein

Everything is connected, especially in the brain. A protein called BAI1 involved in limiting the growth of brain tumors is also critical for spatial learning and memory, researchers have discovered.

Mice missing BAI1 have trouble learning and remembering where they have been. Because of the loss of BAI1, their neurons have changes in how they respond to electrical stimulation, and subtle alterations in parts of the cell needed for information processing.

The findings may have implications for developing treatments for neurological diseases, because BAI1 is part of a protein regulatory network neuroscientists think is connected with autism spectrum disorders.

The results were published online March 9 in Journal of Clinical Investigation.

Erwin Van Meir, PhD, and his colleagues at Winship Cancer Institute of Emory University have been studying BAI1 (brain-specific angiogenesis inhibitor 1) for several years. Part of the BAI1 protein can stop the growth of new blood vessels, which growing cancers need. Normally highly active in the brain, the BAI1 gene is lost or silenced in brain tumors, suggesting that it acts as a tumor suppressor.

The researchers were surprised to find that the brains of mice lacking the BAI1 gene looked normal anatomically. They didn’t develop tumors any faster than normal, and they didn’t have any alterations in their blood vessels, which the researchers had anticipated based on BAI1’s role in regulating blood vessel growth. What they did have was problems with spatial memory.

Read more

Posted on by Quinn Eastman in Cancer, Neuro Leave a comment

Reviving drugs with anti-stroke potential, minus side effects

Neuroprotective drugs might seem impractical or improbable right now, after two big clinical trials testing progesterone in traumatic brain injury didn’t work out. But one close observer of drug discovery is predicting a “coming boom in brain medicines.” Maybe this research, which Emory scientists have been pursuing for a long time, will be part of it.

In the 1990s, neuroscientists identified a class of drugs that showed promise in the area of stroke. NMDA receptor antagonists could limit damage to the brain in animal models of stroke. But one problem complicated testing the drugs in a clinical setting: the side effects included disorientation and hallucinations.

Now researchers have found a potential path around this obstacle. The results were published in Neuron.

“We have found neuroprotective compounds that can limit damage to the brain during ischemia associated with stroke and other brain injuries, but have minimal side effects,” says senior author Stephen Traynelis, PhD, professor of pharmacology at Emory University School of Medicine.

“These compounds are most active when the pH is lowered by biochemical processes associated with injury of the surrounding tissue. This is a proof of concept study that shows this mechanism of action could potentially be exploited clinically in several conditions, such as stroke, traumatic brain injury and subarachnoid hemorrhage.” Read more

Posted on by Quinn Eastman in Neuro Leave a comment

A structure for SorLA/LR11

The importance of the SorLA or LR11 receptor in braking Alzheimer’s was originally defined here at Emory by Jim Lah and Allan Levey’s labs. Japanese researchers recently determined the structure of SorLA and published the results in Nature Structural and Molecular Biology. Their findings point toward a direct role for SorLA in binding toxic circulating beta-amyloid and transporting it to the lysosome for degradation. Hat tip to Alzforum.

Posted on by Quinn Eastman in Neuro Leave a comment

Insecticide-ADHD link, with caveats

Gary Miller’s lab at Emory was the launching pad for this study from Rutgers, published last week in the FASEB Journal, showing a potential connection between a common type of insecticide used at home and in agriculture, pyrethroids, and attention deficit hyperactivity disorder (ADHD).  Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Point mutation in fragile X gene reveals separable functions in brain

A new paper in PNAS from geneticist Steve Warren and colleagues illustrates the complexity of the protein disrupted in fragile X syndrome. It touches on how proposed drug therapies that address one aspect of fragile X syndrome may not be able to compensate for all of them. [For a human side of this story, read/listen to this recent NPR piece from Jon Hamilton.]

Fragile X syndrome is the most common single-gene disorder responsible for intellectual disability. Most patients with fragile X syndrome inherit it because a repetitive stretch of DNA, which is outside the protein-coding portion of the fragile X gene, is larger than usual. The expanded number of CGG repeats silences the entire gene.

However, simple point mutations affecting the fragile X protein are possible in humans as well. In the PNAS paper, Warren’s team describes what happens with a particularly revealing mutation, which allowed researchers to dissect fragile X protein’s multifaceted functions. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Effects of cocaine exposure in adolescent rodents

Much of neuroscientist Shannon Gourley’s work focuses on the idea that adolescence is a vulnerable time for the developing brain. She and graduate student Lauren DePoy recently published a paper in Frontiers in Pharmacology showing that in adolescent rodents, cocaine exposure can cause the loss of dendritic arbors in part of the brain important for decision-making.

The researchers examined neurons in the orbitofrontal cortex, a region of the brain thought to be important for “linking reward to hedonic experience.” It was known that stimulants such as cocaine can cause the loss of dendritic spines: small protrusions that are critical for communication and interaction between neurons.

“To make an analogy, it’s like a tree losing some of its leaves,” Gourley writes. “Lauren’s work shows for the first time that if cocaine is given in adolescence, it can cause the loss of dendrite arbors – as if entire branches are being cut from the tree.”

The mice are exposed to cocaine over the course of five days in early adolescence, and then their behavior is studied in adulthood. This level of cocaine exposure leads to impairments in instrumental task reversal, a test where mice need to change their habits (which chamber they poke their noses into) to continue receiving food pellets.

The findings suggest a partial explanation for the increased risk of dependence in people who start using cocaine during adolescence.

Posted on by Quinn Eastman in Neuro Leave a comment

Going meta

Just before Thanksgiving, Slate writer Katy Waldman had a piece summarizing the growing body of evidence that linguistic metaphors reflect how we actually use our brains.

Emory neuroscientist Krish Sathian and his colleagues have been major contributors to this field (“conceptual metaphor theory”). In 2012, he and Simon Lacey published their brain imaging study, which found that when people listened to sentences involving touch metaphors (“having a rough day”), the parts of the brain involved in the sense of touch were activated. NPR’s Jon Hamilton talked about these findings with him in 2013.

At the recent Society for Neuroscience meeting, Sathian discussed his team’s ongoing work on how the brain processes metaphors that make references to body parts (head, face, arm, hand, leg, foot), as part of a nano symposium on language.

Posted on by Quinn Eastman in Neuro Leave a comment

Strategy to defend vs double hit at beginning of life

Chorioamnionitis is a complication of pregnancy: inflammation of the membranes surrounding the fetus, caused by a bacterial infection. It has the potential to inflict damage to the brain of the fetus, especially when combined with fetal hypoxia, and is a known risk factor for developing cerebral palsy.

Chia-Yi (Alex) Kuan and his team, who study fetal brain injury in the Department of Pediatrics, have a new paper in Journal of Neuroscience on a strategy for inhibiting fetal brain inflammation. Postdoctoral fellows Dianer Yang, Yu-Yo Sun and Siddhartha Kumar Bhaumik are co-first authors.

The researchers show that a type of immune cells called Th17 cells seems to be driving inflammation because the rest of the fetal immune system is still immature. A marker of Th17 cells is elevated in blood samples from human infants with chorioamnionitis, the researchers found. Th17 cells are thought to be important for both autoimmunity and anti-microbial responses.

A drug called fingolimod, which stops immune cells from circulating out of the lymph nodes, was effective in reducing inflammation-induced fetal brain injury in animal models. Fingolimod has been approved by the FDA for use with multiple sclerosis and has been studied in clinical trials of kidney transplantation. The authors write that it may be a potential add-on to hypothermia as a treatment for infants in danger of hypoxia + infection-induced brain damage.

Posted on by Quinn Eastman in Immunology, Neuro Leave a comment

Acidity of aging leads to new Alzheimer’s drug target

Pathologist Keqiang Ye and his colleagues have been studying the functions of an enzyme called AEP, or asparagine endopeptidase, in the brain. AEP is activated by acidic conditions, such as those induced by stroke or seizure.

AEP is a protease. That means it acts as a pair of scissors, snipping pieces off other proteins. In 2008, his laboratory published a paper in Molecular Cell describing how AEP’s acid-activated snipping can unleash other enzymes that break down brain cells’ DNA.

Following a hunch that AEP might be involved in neurodegenerative diseases, Ye’s team has discovered that AEP also acts on tau, which forms neurofibrillary tangles in Alzheimer’s disease.

“We were looking for additional substrates for AEP,” Ye says. “We knew it was activated by acidosis. And we had read in the literature that the aging brain tends to be more acidic, especially in Alzheimer’s.”

The findings, published in Nature Medicine in October, point to AEP as a potential target for drugs that could slow the advance of Alzheimer’s, and may also lead to improved diagnostic tools. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Explainer: the locus coeruleus

The locus coeruleus is a part of the brain that has been getting a lot of attention recently from Emory neuroscience researchers.

The locus coeruleus is the biggest source of the neurotransmitter norepinephrine in the brain. Located deep in the brainstem, it has connections all over the brain, and is thought to be involved in arousal and attention, stress, memory, the sleep-wake cycle and balance.

Researchers interested in neurodegenerative disease want to look at the locus coeruleus because it may be one of the first structures to degenerate in diseases such as Alzheimer’s and Parkinson’s. In particular, the influential studies of German neuro-anatomist Heiko Braak highlight the locus coeruleus as a key “canary in the coal mine” indicator of neurodegeneration.

That’s why neurologist Dan Huddleston, working with biomedical imaging specialists Xiangchuan Chen and Xiaoping Hu and colleagues at Emory, has been developing a method for estimating the volume of the locus coeruleus by magnetic resonance imaging (MRI). Their procedure uses MRI tuned in such a way to detect the pigment neuromelanin (see panel), which accumulate in both the locus coeruleus and in the substantia nigra. Read more

Posted on by Quinn Eastman in Neuro Leave a comment