Schizophrenia Genetic Networks Identified; Connection to Autism Found

Although schizophrenia is highly genetic in origin, the genes involved in the disorder have been difficult to identify. In the past few years, researchers have implicated several genes, but it is unclear how they act to produce the disorder. A new study by researchers at Columbia University Medical Center identifies affected gene networks and provides insight into the molecular causes of the disease.

The paper was published in the online edition of the journal Nature Neuroscience.

Using an unbiased collection of hundreds of mutations associated with schizophrenia, the Columbia researchers applied a sophisticated computational approach to uncover hidden relationships among seemingly unrelated genes. The analysis revealed that many of the genes mutated in schizophrenia are organized into two main networks, which take part in a few key processes, including axon guidance, synapse function, neuron mobility, and chromosomal modification.

The study also uncovered an intriguing connection between schizophrenia and autism. “If we hadn’t known that these were two different diseases, and had put all the mutations into a single analysis, it would have come up with very similar networks,” said the study’s senior author, Dennis Vitkup, PhD, associate professor in the Department of Biomedical Informatics, the Center for Computational Biology and Bioinformatics, and the Columbia Initiative in Systems Biology at Columbia University Medical Center. “It shows how closely the autism and schizophrenia genetic networks are intertwined,” he added.

Newborn Neurons — Even in the Adult Aging Brain - are Critical for Memory

Newly generated, or newborn neurons in the adult hippocampus are critical for memory retrieval, according to a study led by Stony Brook University researchers published online in Nature Neuroscience. The functional role of newborn neurons in the brain is controversial, but in “Optical controlling reveals time-dependent roles for adult-born dentate granule cells,” the researchers detail that by ‘silencing’ newborn neurons, memory retrieval was impaired. The findings support the idea that the generation of new neurons in the brain may be crucial to normal learning and memory processes.

Previous research by the study’s lead investigator Shaoyu Ge, PhD, Assistant Professor in the Department of Neurobiology & Behavior at Stony Brook University, and others have demonstrated that newborn neurons form connections with existing neurons in the adult brain. To help determine the role of newborn neurons, Dr. Ge and colleagues devised a new optogenetic technique to control newborn neurons and test their function in the hippocampus, one of the regions of the brain that generates new neurons, even in the adult aging brain.

“Significant controversy has surrounded the functional role of newborn neurons in the adult brain,” said Dr. Ge. “We believe that our study results provide strong support to the idea that new neurons are important for contextual fear memory and spatial navigation memory, two essential aspects of memory and learning that are modified by experience.

“Our findings could also shed light on the diagnosis and treatment of conditions common to the adult aging brain, such as dementia and Alzheimer’s disease,” he said.

It’s Not Just What You Eat, But When You Eat It: Penn Study Shows Link Between Fat Cell and Brain Clock Molecules

Fat cells store excess energy and signal these levels to the brain. In a new study this week in Nature Medicine, Georgios Paschos PhD, a research associate in the lab of Garret FitzGerald, MD, FRS director of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, shows that deletion of the clock gene Arntl, also known as Bmal1, in fat cells, causes mice to become obese, with a shift in the timing of when this nocturnal species normally eats. These findings shed light on the complex causes of obesity in humans.

The Penn studies are surprising in two respects. “The first is that a relatively modest shift in food consumption into what is normally the rest period for mice can favor energy storage,” says Paschos. “Our mice became obese without consuming more calories.” Indeed, the Penn researchers could also cause obesity in normal mice by replicating the altered pattern of food consumption observed in mice with a broken clock in their fat cells.

This behavioral change in the mice is somewhat akin to night-eating syndrome in humans, also associated with obesity and originally described by Penn’s Albert Stunkard in 1955.

The second surprising observation relates to the molecular clock itself. Traditionally, clocks in peripheral tissues are thought to follow the lead of the “master clock” in the SCN of the brain, a bit like members of an orchestra following a conductor. “While we have long known that peripheral clocks have some capacity for autonomy – the percussionist can bang the drum without instructions from the conductor – here we see that the orchestrated behavior of the percussionist can, itself, influence the conductor,” explains FitzGerald.

A better brain implant: Slim electrode cozies up to single neurons

A thin, flexible electrode developed at the University of Michigan is 10 times smaller than the nearest competition and could make long-term measurements of neural activity practical at last.

This kind of technology could eventually be used to send signals to prosthetic limbs, overcoming inflammation larger electrodes cause that damages both the brain and the electrodes.

The main problem that neurons have with electrodes is that they make terrible neighbors. In addition to being enormous compared to the neurons, they are stiff and tend to rub nearby cells the wrong way. The resident immune cells spot the foreigner and attack, inflaming the brain tissue and blocking communication between the electrode and the cells.

The new electrode developed by the teams of Daryl Kipke, a professor of biomedical engineering, Joerg Lahann, a professor of chemical engineering, and Nicholas Kotov, the Joseph B. and Florence V. Cejka Professor of Engineering, is unobtrusive and even friendly in comparison. It is a thread of highly conductive carbon fiber, coated in plastic to block out signals from other neurons. The conductive gel pad at the end cozies up to soft cell membranes, and that close connection means the signals from brain cells come in much clearer.

"It’s a huge step forward," Kotov said. "This electrode is about seven microns in diameter, or 0.007 millimeters, and its closest competitor is about 25 to 100 microns."

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Preschoolers’ Counting Abilities Relate to Future Math Performance

Along with reciting the days of the week and the alphabet, adults often practice reciting numbers with young children. Now, new research from the University of Missouri suggests reciting numbers is not enough to prepare children for math success in elementary school. The research indicates that counting, which requires assigning numerical values to objects in chronological order, is more important for helping preschoolers acquire math skills.

“Reciting means saying the numbers from memory in chronological order, whereas counting involves understanding that each item in the set is counted once and that the last number stated is the amount for the entire set,” said Louis Manfra, an assistant professor in MU’s Department of Human Development and Family Studies. “When children are just reciting, they’re basically repeating what seems like a memorized sentence. When they’re counting, they’re performing a more cognitive activity in which they’re associating a one-to-one correspondence with the object and the number to represent a quantity.”

“Counting gives children stronger foundations when they start school,” Manfra said. “The skills children have when they start kindergarten affect their trajectories through early elementary school; therefore, it’s important that children start with as many skills as possible.”

The study, “Associations between Counting Ability in Preschool and Mathematic Performance in First Grade among a Sample of Ethnically Diverse, Low-Income Children,” will be published in an upcoming issue of the Journal of Research in Childhood Education.

Inflammation for Regeneration

The secret to zebrafish’s remarkable capacity for repairing their brains is inflammation, according to a report published online in Science. Neural stem cells in the fish’s brains express a receptor for inflammatory signaling molecules, which prompt the cells to multiply and develop into new neurons.

“This is a very interesting paper,” said Guo-li Ming, a professor of neurology and neuroscience at The Johns Hopkins University in Baltimore, who was not involved in the study. “It is well known that fish have this ability to self-repair, and this paper provides a mechanism,” she said.

Zebrafish, like many other vertebrates, are able to regenerate a variety of body tissues, including their brains. In fact, said Michael Brand, a professor of developmental genetics at the Technische Universität in Dresden, Germany, “mammals are the ones that seem to have lost this ability—they are kind of the odd ones out.” Given the therapeutic potential of neuron regeneration for patients with brain or spinal injuries, “we’d like to figure out if we can somehow reactivate this potential in humans,” Brand said.

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Methamphetamine vaccine shows promise

Methamphetamine is one of the most addictive and thus commonly-used street drugs – according to the United Nations Office on Drugs and Crime, there are currently nearly 25 million meth addicts worldwide. Help may be on the way, however. Scientists from The Scripps Research Institute have had success in using a methamphetamine vaccine to block the effects on meth on lab rats.

The vaccine works by allowing the body’s immune system to attack methamphetamine molecules in the bloodstream, keeping them from entering the nervous system. This keeps the meth from affecting the user’s brain, and thus removes the incentive for using the drug.

Ordinarily, meth molecules are too small to evoke an antibody response from the body. The vaccine, known as M6, gets around this by linking a meth-related chemical to a larger carrier molecule that does cause an antibody response. Once the antibodies are in the bloodstream, they attack both the carrier molecules and the actual meth molecules.

In tests on rats, M6 blocked two of the typical effects of the drug – loss of the ability to regulate body temperature, and in increase in physical activity. In another ongoing Scripps study, meth-targeting antibodies were grown in cultured cells in a lab, then injected into rats in a concentrated dose. This approach also blocked the effects of the drug.

More animal trials are planned for now, with the possibility of human trials occurring in the future.

Brain Power: From Neurons to Networks is a 10-minute film and an accompanying TED Book. Based on new research on how to best nurture children’s brains from Harvard University’s Center on the Developing Child and University of Washington’s I-LABS, the film explores the parallels between a child’s brain development and the development of the global brain of Internet, offering insights into the best ways to shape both. The film and TEDBook launched at the California Academy of Sciences on November 8, 2012.