Sleep and dreaming: The how, where and why

Within a few hours of reading this you will lose consciousness and slip into a strange twilight world. Where does your mind go during that altered state – or more accurately states – we call sleep? And what is so vital about it that we must spend a third of our lives sleeping? In these articles, we review the latest ideas on why we sleep and look at new ways to enhance its benefits.

Sensitive Males Provide Clues to Mind Reading in Birds

The male Eurasian jay is an accommodating fellow. When his mate has been feasting steadily on mealworm larvae, he realizes that she’d now prefer to dine on wax moth larvae, which he feeds her himself. The finding adds to a small but growing number of studies that show that some animals have something like the human ability to understand what others are thinking.

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With Identical Neurons, Two Worm Species Live Very Different Lives

Two species of worms have the same set of 20 neurons that control their foregut (a digestive organ located, naturally, near the front end of the worm). The way those neurons are wired, though, completely changes their behavior.

Caenorhabditis elegans eats bacteria, while its worm cousin Pristionchus pacificus, while able to subsist on bacteria, also eats other worms. While C. elegans uses a grinder to break up bacteria, P. pacificus develops teeth-like denticles to puncture its prey.

"These species are separated by 200 to 300 million years, but have the same cells," researcher Ralf Sommer told New Scientist. However, they found the synapses were wired vastly differently, leading to a substantial change in the way information flows through their neural system.

In P. pacificus, neural signals pass through more cells before reaching the muscles. That suggests that it’s perfuming more complex motor functions, according to the European Molecular Biology Lab’s Detlev Arendt.

The paper can be found in the January 17 issue of Cell.

Finding the way to memory

Our ability to learn and form new memories is fully dependent on the brain’s ability to be plastic – that is to change and adapt according to new experiences and environments. A new study from the Montreal Neurological Institute – The Neuro, McGill University, reveals that DCC, the receptor for a crucial protein in the nervous system known as netrin, plays a key role in regulating the plasticity of nerve cell connections in the brain. The absence of DCC leads to the type of memory loss experienced by Dr. Brenda Milner’s famous subject HM.  Although HM’s memory loss resulted from the removal of an entire brain structure, this study shows that just removing DCC causes the same type of memory deficit. The finding published in this week’s issue of Cell Reports, extends Dr. Milner’s seminal finding to another level, revealing a key part of the molecular basis for learning and memory.

Although both netrin and DCC are essential for normal development (in terms of guiding nerve cell growth) until now their function in the adult brain was not known. Dr. Tim Kennedy, lead researcher and neuroscientist at The Neuro, contributed to the discovery of netrins as a young post-doctoral fellow. This new study reveals the answer to the question that drove him to first start a lab. “I remember that exact moment when I knew I could run a research lab, it was 1993 and I was studying the developing nervous system and I was amazed to spot netrins in the adult brain - raising the important question, ‘what are they doing there?’ 20 years of dedicated research later the answer provides an important piece of the puzzle for understanding our nervous system and neurological disorders.

“The power of this study is that it looks at the animal on all levels, molecular, structural, and behavioural. We show that the netrin receptor DCC is a critical component of synapses between neurons in the adult brain, and is required for synapses to function properly. To demonstrate this, we selectively removed DCC from a specific subset of neurons in the adult mouse brain. This results in progressive degeneration of synapses, leading to defects in synaptic plasticity and memory. The synapses continue to function in that they still communicate but, the synapses cannot adjust or change in response to new experiences. Therefore, you can’t learn anymore.”

Furthermore, DCC deletion from mature neurons results in changes in the shape of specialized protrusions called dendritic spines, and alters the NMDA receptor, a critical trigger for mechanisms that make changes in synaptic strength. Therefore the study reveals that DCC is required to maintain proper synapse morphology or shape, and to regulate the ability of the NMDA receptor to switch on, which ensures activity-dependent synaptic plasticity.

Study Confirms No Transmission of Alzheimer’s Proteins Between Humans

Mounting evidence demonstrates that the pathological proteins linked to the onset and progression of neurodegenerative disorders are capable of spreading from cell-to-cell within the brains of affected individuals and thereby “spread” disease from one interconnected brain region to another. A new study found no evidence to support concerns that these abnormal disease proteins are “infectious” or transmitted from animals to humans or from one person to another. The study by researchers from the Perelman School of Medicine at the University of Pennsylvania, in conjunction with experts from the U.S. Centers for Disease Control and the Department of Health and Human Services, appears online in JAMA Neurology.

Cell-to-cell transmission is a potentially common pathway for disease spreading and progression in diseases like Alzheimer’s (AD) and Parkinson’s (PD) disease as well as frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and other related disorders. It appears that misfolded proteins spread from one cell to another and that the affected neurons become dysfunctional, while these toxic proteins go on to damage other regions of the brain over time.

"By interrogating an existing database with information on a cohort of well-characterized patients, we were able to determine that there is no evidence suggesting the pathology of Alzheimer’s or Parkinson’s can transmit between humans,"  said senior author John Q. Trojanowski, MD, PhD, professor of Pathology and Laboratory Medicine and co-director of the Penn Center for Neurodegenerative Disease Research. "We can now redouble efforts to find treatments, via immunotherapies or other approaches to stop the spreading of these toxic proteins between cells."

In order to verify whether such proteins could potentially be carried from person to person, the team of researchers analyzed data from an existing cohort of patients who had received human growth hormone (hGH) from cadaveric pituitary glands via a national program, as a beneficial treatment for stunted growth, before synthetic hGH was available. Nearly 7,700 patients were treated with cadaver-derived hGH (c-hGH) in the US between 1963 and 1985. In the mid-1980s, more than 200 patients worldwide who had received c-hGH inadvertently contaminated with prion proteins from affected donor pituitary tissue went on to develop an acquired form of Creutzfeldt-Jakob disease (CJD), a rare, degenerative, invariably fatal brain disorder caused by pathological prion proteins that also are the cause of Mad Cow disease. Since then, the cohort has been followed to track any additional cases of CJD, with extensive medical histories for patients over the 30+ years since the c-hGH therapy was stopped after the link to CJD was discovered in 1985.

Damaged Blood Vessels Loaded with Amyloid Worsen Cognitive Impairment in Alzheimer’s Disease

A team of researchers at Weill Cornell Medical College has discovered that amyloid peptides are harmful to the blood vessels that supply the brain with blood in Alzheimer’s disease — thus accelerating cognitive decline by limiting oxygen-rich blood and nutrients. In their animal studies, the investigators reveal how amyloid-ß accumulates in blood vessels and how such accumulation and damage might be ultimately prevented.

Their study, published in the Feb. 4 online edition of the Proceedings of the National Academy of Sciences (PNAS), is the first to identify the role that the innate immunity receptor CD36 plays in damaging cerebral blood vessels and promoting the accumulation of amyloid deposits in these vessels, a condition known as cerebral amyloid angiopathy (CAA).

Importantly, the study provides the rational bases for targeting CD36 to slow or reverse some of the cognitive deficits in Alzheimer’s disease by preventing CAA.

"Our findings strongly suggest that amyloid, in addition to damaging neurons, also threatens the cerebral blood supply and increases the brain’s susceptibility to damage through oxygen deprivation," says the study’s senior investigator, Dr. Costantino Iadecola, the Anne Parrish Titzell Professor of Neurology at Weill Cornell Medical College and director of the Brain and Mind Research Institute at Weill Cornell Medical College and NewYork-Presbyterian Hospital. "If we can stop accumulation of amyloid in these blood vessels, we might be able to significantly improve cognitive function in Alzheimer’s disease patients. Furthermore, we might be able to improve the effectiveness of amyloid immunotherapy, which is in clinical trials but has been hampered by the accumulation of amyloid in cerebral blood vessels."

Mounting scientific evidence shows that changes in the structure and function of cerebral blood vessels contribute to brain dysfunction underlying Alzheimer’s disease, but no one has truly understood how this happens until now.

Chemical reaction keeps stroke-damaged brain from repairing itself

Nitric oxide, a gaseous molecule produced in the brain, can damage neurons. When the brain produces too much nitric oxide, it contributes to the severity and progression of stroke and neurodegenerative diseases such as Alzheimer’s. Researchers at Sanford-Burnham Medical Research Institute recently discovered that nitric oxide not only damages neurons, it also shuts down the brain’s repair mechanisms. Their study was published by the Proceedings of the National Academy of Sciences the week of February 4.

“In this study, we’ve uncovered new clues as to how natural chemical reactions in the brain can contribute to brain damage—loss of memory and cognitive function—in a number of diseases,” said Stuart A. Lipton, M.D., Ph.D., director of Sanford-Burnham’s Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and a clinical neurologist.

Lipton led the study, along with Sanford-Burnham’s Tomohiro Nakamura, Ph.D., who added that these new molecular clues are important because “we might be able to develop a new strategy for treating stroke and other disorders if we can find a way to reverse nitric oxide’s effect on a particular enzyme in nerve cells.”

Nitric oxide inhibits the neuroprotective ERK1/2 signaling pathway

Learning and memory are in part controlled by NMDA-type glutamate receptors in the brain. These receptors are linked to pores in the nerve cell membrane that regulate the flow of calcium and sodium in and out of the nerve cells. When these NMDA receptors get over-activated, they trigger the production of nitric oxide. In turn, nitric oxide attaches to other proteins via a reaction called S-nitrosylation, which was first discovered by Lipton and colleagues. When those S-nitrosylated proteins are involved in cell survival and lifespan, nitric oxide can cause brain cells to die prematurely—a hallmark of neurodegenerative disease.

In their latest study, Lipton, Nakamura and colleagues used cultured neurons as well as a living mouse model of stroke to explore nitric oxide’s relationship with proteins that help repair neuronal damage. They found that nitric oxide reacts with the enzyme SHP-2 to inhibit a protective cascade of molecular events known as the ERK1/2 signaling pathway. Thus, nitric oxide not only damages neurons, it also blocks the brain’s ability to self-repair.

Molecule key to sustaining brain communication

Scientists have discovered the powerful role the molecule Myosin VI plays in communication between nerve cells in the brain.

Researchers at the University of Queensland’s (UQ) Queensland Brain Institute (QBI) have found that Myosin VI is integral to maintaining the neurotransmitter release that allows neurons to pass on information to other neurons.

The discovery made by Vanesa Tomatis, a PhD student in Associate Professor Frederic Meunier’s laboratory, demonstrates how Myosin VI has the impressive ability to anchor secretory vesicles that are at least 5,000 times greater in size, near their release site.

"By tethering and anchoring secretory granules, Myosin VI helps to maintain an active pool of vesicles near the plasma membrane, which is key to sustaining communication between neuronal cells," Associate Professor Meunier said.

Associate Professor Meunier and his team are now looking to better understand how the Myosin VI manages to grab and hold vesicles through the use of super resolution microscopy.

They hope the discovery will lead to new ways to reinstate or regulate neuronal communication in various brain disorders.

The paper was published in The Journal of Cell Biology on February 4 2013

(Image credit: Wikipedia)

Human brain is divided on fear and panic

When doctors at the University of Iowa prepared a patient to inhale a panic-inducing dose of carbon dioxide, she was fearless. But within seconds of breathing in the mixture, she cried for help, overwhelmed by the sensation that she was suffocating.

The patient, a woman in her 40s known as SM, has an extremely rare condition called Urbach-Wiethe disease that has caused extensive damage to the amygdala, an almond-shaped area in the brain long known for its role in fear. She had not felt terror since getting the disease when she was an adolescent.

In a paper published online Feb. 3 in the journal Nature Neuroscience, the UI team provides proof that the amygdala is not the only gatekeeper of fear in the human mind. Other regions—such as the brainstem, diencephalon, or insular cortex—could sense the body’s most primal inner signals of danger when basic survival is threatened.

“This research says panic, or intense fear, is induced somewhere outside of the amygdala,” says John Wemmie, associate professor of psychiatry at the UI and senior author on the paper. “This could be a fundamental part of explaining why people have panic attacks.”

If true, the newly discovered pathways could become targets for treating panic attacks, post-traumatic stress syndrome, and other anxiety-related conditions caused by a swirl of internal emotional triggers.

“Our findings can shed light on how a normal response can lead to a disorder, and also on potential treatment mechanisms,” says Daniel Tranel, professor of neurology and psychology at the UI and a corresponding author on the paper.

NEUROSPHERE

Four differently stained images featuring a neurosphere and primary culture cells derived form glioblastoma – stained by MGMT/FITC, GFAP y3 and DAPT.

Image Courtesy: Marek Molcanyi, Marina Penner, Sandrine Pacchnini, Clemens Reinshagen, John Ivan Bianco, University of Cologne, Germany

(Source: leica-microsystems.com)