Posts tagged reelin
Articles and news from the latest research reports.
Protein reelin rescues cognitive impairment in animal models of Alzheimer’s disease
The scientists Eduardo Soriano and Lluís Pujadas, from the University of Barcelona (UB), and the “Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas” (CIBERNED) have led research into the role of reelin in animal models of Alzheimer’s disease.
Published today in the journal Nature Communications, the study demonstrates how an increase in the levels of reelin—a protein that is essential for cerebral cortex plasticity—has the capacity to restore cognitive capacity in mouse models of Alzheimer’s disease, delaying amyloid-beta (Αβ) fibril formation in vitro and reducing the accumulation of amyloid deposits in the brains of animals affected by this disease.
The study, which was started four years ago, has involved the collaboration of members of the Peptides and Proteins lab at the Institute for Research in Biomedicine (IRB), namely Bernat Serra-Vidal, PhD student, Ernest Giralt, group leader, and Natàlia Carulla, associate researcher whose investigation focuses on the aggregation of Αβ. Alzheimer’s disease, which affects approximately 500,000 people in Spain, is characterised by the loss of neural connections and by neuronal death, both associated mainly with the formation of senile plaques (extracellular deposits of Aβ) and the presence of neurofibrillary tangles (intracellular deposits of tau protein.
In the IRB lab, researchers have performed experiments in vitro to determine whether there is an interaction between Aβ aggregation and reelin. These assays have revealed that reelin interacts with the Aβ peptide, delaying the formation of Aβ fibrils until it is trapped within them. “When reelins becomes trapped in Aβ fibrils, it loses its capacity to strengthen synaptic plasticity. This explains why an increase in reelin expression in the brain may be beneficial,” explain the authors of the study.
The hypotheses from the work in vitro have been tested in vivo using experimental animals. This study is the first to demonstrate a neuroprotective effect of reelin in neurodegenerative disease and, in addition, offers a possible explanation for this protective role.
Researchers Find Surprising Role of Critical Brain Protein
If the violins were taken away from the musicians performing Beethoven’s 9th symphony, the resulting composition would sound very different. If the violins were left on stage but the violinists were removed, the same mutant version of the symphony would be heard.
But what if it ended up sounding like “Hey Jude” instead?
This sort of surprise is what scientists from the Virginia Tech Carilion Research Institute had during what they assumed to be a routine experiment in neurodevelopment. Previous studies had shown that the glycoprotein Reelin is crucial to developing healthy neural networks. Logically, taking away the two receptors that Reelin is known to act on early in the brain’s development should create the same malformations as taking away Reelin itself.
It didn’t.
“We conducted the experiment thinking we’d see the same defects for both cases – Reelin deficiency and its receptors’ deletion – but we didn’t,” said Michael Fox, an associate professor at the research institute and the lead author of the study. “If you take away the receptors instead of the targeting molecule, you get an entirely separate set of abnormalities. The results raise the question of the identity of other molecules with which Reelin and the two receptors are interacting.”
The study, first published online in June in Neural Development, could prove useful for the development of therapies and diagnostics to combat brain disease.
In the early stages of neural development, neurons grow from the retina to a small portion of the brain called the thalamus. All sensory information coming into the brain gets routed through this region, before being transmitted to the cerebral cortex for further processing. Because these retinal neurons carry specific types of information, they must connect to specific places in the thalamus, which Reelin helps them find.
In the experiment, the scientists bred mice lacking both Reelin receptors known to be critical for neurons to navigate their targets during development. The scientists expected the neurons in the mutants to become lost and unable to find their targets, which is what happens in Reelin-deficient mice. Instead, the neurons were able to locate their targets, but those targets had wandered off.
While these results were surprising, they weren’t the most interesting of the experiment. Although most neurons look the same to people without advanced training in neuroscience, many different types are intermixed in distinct regions with strict borders. How these borders are formed, however, is still an open question.
“Many of us have questioned how you can have such a crisp boundary between two regions of the brain,” said Jianmin Su, a research assistant professor at the research institute and first author of the study. “I always thought it was a large number of cells creating some kind of cue or environment, but that isn’t what this experiment indicates.”
In the mice without the Reelin receptors, neurons from one part of the thalamus migrated to an area where they weren’t supposed to be. Even though only a handful of neurons were misplaced, they did not mingle with their new neighbors. They stayed separate.
“The result is a baffling curiosity that nobody in the lab expected – just how distinct these little regions can be,” Fox said. “How do just a few cells create such a barrier? How many cells does it take? Maybe these little islands can teach us something about how you create boundaries between larger regions of functionally similar cells.”
This experiment isn’t the only example Fox has had recently of neurons invading regions in which they weren’t supposed to be. In a second experiment, researchers examined how neurons from the cortex connect to the thalamus during the initial stages of development.
And neurons seem to be polite.
The results showed that neurons from the cortex grow to the edge of the part of the thalamus dedicated to visual signals, called the dorsal lateral geniculate nucleus, but then stop. In fact, they stay on standby for nearly two weeks before making their way into the region. It seems as though they’re waiting for the retinal neurons to make their connections before beginning to make their own. If researchers surgically removed the eyes or genetically removed the retinal cells connecting the eyes to the thalamus, neurons from the cortex invaded more than a week earlier than they were supposed to.
“It turns out that the cortical neurons are waiting for the retinal axons to mature and find the most appropriate spots to connect before they’re allowed to come in,” said Fox. “There’s some form of instructional role that retinal axons play in the timing of the cortical axons entering.”
(Source: newswise.com)