Gladstone Scientists Identify Biological Mechanism that Plays Key Role in Early-Onset Dementia: Findings explain how protein deficiency contributes to neurodegenerative disease

Using animal models, scientists at the Gladstone Institutes have discovered how a protein deficiency may be linked to frontotemporal dementia (FTD)—a form of early-onset dementia that is similar to Alzheimer’s disease. These results lay the foundation for therapies that one day may benefit those who suffer from this and related diseases that wreak havoc on the brain.

As its name implies, FTD is a fatal disease that destroys cells, or neurons, that comprise the frontal and temporal lobes of the brain—as opposed to Alzheimer’s which mainly affects brain’s memory centers in the hippocampus. Early symptoms of FTD include personality changes, such as increased erratic or compulsive behavior. Patients later experience difficulties speaking and reading, and often suffer from long-term memory loss. FTD is usually diagnosed between the ages of 40 and 65, with death occurring within 2 to 10 years after diagnosis. No drug exists to slow, halt or reverse the progression of FTD.

A new study led by Gladstone Senior Investigator Robert V. Farese, Jr., MD, offers new hope in the fight against this and other related conditions. In the latest issue of the Journal of Clinical Investigation, Dr. Farese and his team show how a protein called progranulin prevents a class of cells called microglia from becoming “hyperactive.” Without adequate progranulin to keep microglia in check, this hyperactivity becomes toxic, causing abnormally prolonged inflammation that destroys neurons over time—and leads to debilitating symptoms.

Brain connectivity predicts reading skills

The growth pattern of long-range connections in the brain predicts how a child’s reading skills will develop, according to research published today in Proceedings of the National Academy of Sciences

Literacy requires the integration of activity in brain areas involved in vision, hearing and language. These areas are distributed throughout the brain, so efficient communication between them is essential for proficient reading.

Jason Yeatman, a neuroscientist at Stanford University in California, and his colleagues studied how the development of reading ability relates to growth in the brain’s white-matter tracts, the bundles of nerve fibres that connect distant regions of the brain.

They tested how the reading skills of 55 children aged between 7 and 12 years old developed over a three-year period. There were big differences in reading ability between the children, and these differences persisted — the children who were weak readers relative to their peers at the beginning of the study were still weak three years later.

The researchers also scanned the brains of 39 of the children at least three times during the same period, to visualize the growth of two major white-matter tracts: the arcuate fasciculus, which conects the brain’s language centres, and the inferior longitudinal fasciculus, which links the language centres with the parts of the brain that process visual information.

Differences in the growth of both tracts could predict the variations in reading ability. Strong readers started off with a weak signal in both tracts on the left side of the brain, which got stronger over the three years. Weaker readers exhibited the opposite pattern.

A new field of developmental neuroscience changes our understanding of the early years of human life

Biological Embedding of Early Social Adversity: From Fruit Flies to Kindergartners, a special volume published in the Proceedings of the National Academy of Sciences (1, 2, 3) and authored largely by researchers of the Canadian Institute for Advanced Research (CIFAR), sets out an emerging new field of the developmental science of childhood adversity.

The implications of the research are far reaching, from new approaches to learning and language acquisition, to new considerations for the health effects of social environments affecting large populations, and policies for early childhood care and education.

"CIFAR’s multidisciplinary and international program in early childhood development is transforming our understanding of how early life experiences affect the development of the brain and in so doing set a lifelong trajectory," says Dr. Alan Bernstein, CIFAR President & CEO. "This research is providing the scientific basis for public policy concerning the critical window to provide the optimal conditions that will enable our children to grow up to be well-adjusted, well-educated and productive individuals."

Moms’ depression affects babies’ language development – but so does anti-depressant drug – research shows

Janet Werker and her colleagues played recordings to babies when they were still in the womb.

Then the University of British Columbia psychologist and her team tested babies’ ability to discriminate between English and French when the infants were just six and 10 months old.

The findings, published Monday, are striking.

Both maternal depression, which affects up to 20 per cent of pregnant women, and treating mothers with a common anti-depressant drug threw off infants’ language development, Werker and her colleagues at the University of British Columbia and Harvard University report in the U.S. Proceedings of the National Academy of Sciences.

Babies of depressed mothers were slow to reach language development “milestones,” they report. And babies of mothers taking antidepressants known as serotonin reuptake inhibitors (SRIs) reached milestones months early, they report.

Canadian Team Reports World’s First Successful Clinical Trial to Protect the Brain From Damage Caused by Stroke

A team of Canadian scientists and clinicians, led by Dr. Michael Hill of the Calgary Stroke Program at Foothills Medical Centre and University of Calgary’s Hotchkiss Brain Institute (HBI), have demonstrated that a neuroprotectant drug, developed by Dr. Michael Tymianski at the Krembil Neuroscience Centre, located at the Toronto Western Hospital, protects the human brain against the damaging effects of stroke.

The study, “Safety and efficacy of NA-1 for neuroprotection in iatrogenic stroke after endovascular aneurysm repair: a randomized controlled trial,” published online today in The Lancet Neurology, was conducted concurrently with a laboratory study published in Science Translational Medicine, that predicted the benefits of the stroke drug.

This landmark clinical trial was a randomized, double blinded, multi-centre trial that was conducted in Canada and the USA. The study evaluated the effectiveness of NA-1[Tat-NR2B9c] when it was administered after the onset of small strokes that are incurred by patients who undergo neurointerventional procedures to repair brain aneurysms. This type of small ischemic stroke occurs in over 90% of aneurysm patients after such a procedure, but usually does not cause overt neurological disability.

Gender stereotypes and nature vs. nurture

Leading neuroscientist Professor Simon Baron Cohen will be taking part in a debate at this year’s Cambridge Festival of Ideas on whether science has been used to promote gender stereotypes.

Neuroscientists have been criticised in recent books by feminist writers such as Natasha Walter’s Living Dolls for bolstering gender stereotypes.

Simon Baron Cohen, professor of developmental psychopathology at the University of Cambridge, says critics who argue that gender difference is all a question of socialisation are in danger of oversimplifying the interaction of biology and experience. He says: “Some gender differences in the mind and behaviour may in part be the result of our biology (prenatal hormones and genes) interacting with our experience. The old nature vs. nurture debate is absurdly simplistic and a moderate position recognises the interaction of both.

He adds that he is wary of neuroscience research being used to bolster traditional gender stereotypes. He says: “The main goal of neuroscience is to understand the mind, and is certainly not to bolster traditional views.”

The aim of the Festival, which is in its fourth year, is to celebrate the Arts, Humanities and Social Sciences. Most of the over 170 events running during the Festival are free, but some debates may need to be prebooked.

More information: www.cam.ac.uk/festivalofideas
*Gender differences: nature vs nurture takes place from 7.30-9pm at the Babbage Theatre, Downing Street on 30 October.

Rethinking Sleep

SOMETIME in the dark stretch of the night it happens. Perhaps it’s the chime of an incoming text message. Or your iPhone screen lights up to alert you to a new e-mail. Or you find yourself staring at the ceiling, replaying the day in your head. Next thing you know, you’re out of bed and engaged with the world, once again ignoring the often quoted fact that eight straight hours of sleep is essential.

Sound familiar? You’re not alone. Thanks in part to technology and its constant pinging and chiming, roughly 41 million people in the United States — nearly a third of all working adults — get six hours or fewer of sleep a night, according to a recent report from the Centers for Disease Control and Prevention. And sleep deprivation is an affliction that crosses economic lines. About 42 percent of workers in the mining industry are sleep-deprived, while about 27 percent of financial or insurance industry workers share the same complaint.

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Discovery of gatekeeper nerve cells explains the effect of nicotine on learning and memory

Researchers at Uppsala University have, together with Brazilian collaborators, discovered a new group of nerve cells that regulate processes of learning and memory. These cells act as gatekeepers and carry a receptor for nicotine, which can explain our ability to remember and sort information.

The discovery of the gatekeeper cells, which are part of a memory network together with several other nerve cells in the hippocampus, reveal new fundamental knowledge about learning and memory. The study is published today in Nature Neuroscience.

The hippocampus is an area of the brain that is important for consolidation of information into memories and helps us to learn new things. The newly discovered gatekeeper nerve cells, also called OLM-alpha2 cells, provide an explanation to how the flow of information is controlled in the hippocampus.

“It is known that nicotine improves cognitive processes including learning and memory, but this is the first time that an identified nerve cell population is linked to the effects of nicotine”, says Professor Klas Kullander at Uppsala University.