Posts tagged neuroscience

January 30th, 2012

The hippocampus (highlighted in fuchsia) is a key brain structure important to learning, memory and stress response. New research shows that children who were nurtured by their mothers early in life have a larger hippocampus than children who were not nurtured as much. Credit: Washington University Medical School from press release

Source: Neuroscience News

Article Date: 06 Feb 2012 - 0:00 PST

Men and women may be equals, but they often behave differently when it comes to sex and parenting. Now a study of the differences between the brains of male and female mice in the Cell Press journal Cell provides insight into how our own brains might be programmed for these stereotypically different behaviors.

The new evidence shows that the sex hormones - testosterone, estrogen, and progesterone - act in a key region of the brain, switching certain genes on and others off. When the researchers tinkered with each of these genes one by one, animals showed subtle but important shifts in individual sex-specific behaviors, such as how males mate or females care for their pups.

“What this means is that complex behaviors like male mating or maternal care in mice can be deconstructed at the genetic level,” said Nirao Shah of the University of California, San Francisco. The findings present a cellular and molecular representation of gender that is remarkable in its complexity, the researchers say.

Shah’s team made these discoveries after screening mouse brains for genes that show differences in expression in males versus females. The researchers focused specifically on the hypothalamus, a region previously implicated in the control of sex-specific behaviors. Their screen produced a list of 16 genes with clear sex differences in distinct neurons in the hypothalamus. Surprisingly, Shah’s team found that many of these genes also show sex differences in the amygdala, a part of the brain important for emotions.

In further studies, the researchers examined the effects of a subset of these individual genes. Mice missing only one of these 16 genes seemed to behave normally. But upon closer observation, these mice showed significant differences in sex-specific behaviors. For instance, Shah explained, females mutant for one gene took longer to return their pups to the nest and to fight off intruders. “They still take care of their pups, but less effectively,” he said.

In other experiments, deletion of a single gene produced females that were two-fold less receptive to mating with males. Similarly, males mutant for another gene were less interested in females. Together these results mean that sex-specific behaviors can be controlled in modular fashion, such that the loss of any one gene leads to subtle but potentially important changes.

“At the superficial level, the mice appear normal, but this is pretty significant variation in behavior,” Shah said. It suggests that variation in such genes might explain not just differences between the sexes, but also differences in behaviors within one sex or the other - why some male mice are more aggressive than other males or some females more attentive to their offspring than other females.

The researchers don’t yet know exactly how these differences in gene expression lead to those differences in behavior, although Shah says some of the genes are known to be involved in sending or receiving neural messages in the brain. It also remains to be seen how the male and female gene expression programs might be influenced by the animals’ social interactions and experiences.

There is still a lot to learn about what makes males and females tick. “This gene list of sex differences in the brain is probably just a small subset of what we will eventually unearth,” Shah said.  

Source: Medical News Today

Article Date: 05 Feb 2012 - 0:00 PST

Drinking decaffeinated coffee may improve brain energy metabolism associated with diabetes type 2, according to a study published in Nutritional Neuroscience and carried out by researchers at Mount Sinai School of Medicine. Brain energy metabolism is a dysfunction with a known risk factor for dementia and other neurodegenerative disorders like Alzheimer’s disease.

Giulio Maria Pasinetti, MD, PhD, and team decided to investigate whether dietary supplementation with a standard decaffeinated coffee prior to diabetes onset could improve insulin resistance and glucose utilization in mice with diet-induced type 2 diabetes.

The mice were given the supplement for five months, after which the researchers assessed the animals’ brain’s genetic response. They discovered that the brain could metabolize glucose more effectively and that it was used for cellular energy in the brain. People with type 2 diabetes have reduced glucose utilization in the brain, which often leads to neurocognitive problems.

Dr. Pasinetti stated:

"Impaired energy metabolism in the brain is known to be tightly correlated with cognitive decline during aging and in subjects at high risk for developing neurodegenerative disorders. This is the first evidence showing the potential benefits of decaffeinated coffee preparations for both preventing and treating cognitive decline caused by type 2 diabetes, aging, and/or neurodegenerative disorders."

Drinking coffee is not recommended for everyone, because of its association with cardiovascular health risks, including elevated blood cholesterol and blood pressure, both of which result in a higher risk of developing heart disease, stroke, and premature death. However, these negative effects have mainly been caused because of the high caffeine content of coffee - the study findings prove that some components in decaffeinated coffee have beneficial health factors for mice.

Dr. Pasinetti wants to investigate whether decaffeinated coffee as a dietary supplement in humans can act as a preventive measure.

He concludes:

"In light of recent evidence suggesting that cognitive impairment associated with Alzheimer’s disease and other age-related neurodegenerative disorders may be traced back to neuropathological conditions initiated several decades before disease onset, developing preventive treatments for such disorders is critical."

Petra Rattue 

Source: Medical News Today

ScienceDaily (Feb. 3, 2012) — When a friend tells you she had a rough day, do you feel sandpaper under your fingers? The brain may be replaying sensory experiences to help understand common metaphors, new research suggests.

Regions of the brain activated by hearing textural metaphors are shown in green. Yellow and red show regions activated by sensory experience of textures visually and through touch. (Credit: Image courtesy of Emory University)

Linguists and psychologists have debated how much the parts of the brain that mediate direct sensory experience are involved in understanding metaphors. George Lakoff and Mark Johnson, in their landmark work ‘Metaphors we live by’, pointed out that our daily language is full of metaphors, some of which are so familiar (like “rough day”) that they may not seem especially novel or striking. They argued that metaphor comprehension is grounded in our sensory and motor experiences.

New brain imaging research reveals that a region of the brain important for sensing texture through touch, the parietal operculum, is also activated when someone listens to a sentence with a textural metaphor. The same region is not activated when a similar sentence expressing the meaning of the metaphor is heard.

The results were published online this week in the journal Brain & Language.

"We see that metaphors are engaging the areas of the cerebral cortex involved in sensory responses even though the metaphors are quite familiar," says senior author Krish Sathian, MD, PhD, professor of neurology, rehabilitation medicine, and psychology at Emory University. "This result illustrates how we draw upon sensory experiences to achieve understanding of metaphorical language."

Sathian is also medical director of the Center for Systems Imaging at Emory University School of Medicine and director of the Rehabilitation R&D Center of Excellence at the Atlanta Veterans Affairs Medical Center.

Seven college students who volunteered for the study were asked to listen to sentences containing textural metaphors as well as sentences that were matched for meaning and structure, and to press a button as soon as they understood each sentence. Blood flow in their brains was monitored by functional magnetic resonance imaging. On average, response to a sentence containing a metaphor took slightly longer (0.84 vs 0.63 seconds).

In a previous study, the researchers had already mapped out, for each of these individuals, which parts of the students’ brains were involved in processing actual textures by touch and sight. This allowed them to establish with confidence the link within the brain between metaphors involving texture and the sensory experience of texture itself.

"Interestingly, visual cortical regions were not activated by textural metaphors, which fits with other evidence for the primacy of touch in texture perception," says research associate Simon Lacey, PhD, the first author of the paper.

The researchers did not find metaphor-specific differences in cortical regions well known to be involved in generating and processing language, such as Broca’s or Wernicke’s areas. However, this result doesn’t rule out a role for these regions in processing metaphors, Sathian says. Also, other neurologists have seen that injury to various areas of the brain can interfere with patients’ understanding of metaphors.

"I don’t think that there’s only one area responsible for metaphor processing," Sathian says. "Actually, several recent lines of research indicate that engagement with abstract concepts is distributed around the brain." "I think our research highlights the role of neural networks, rather than a single area of the brain, in these processes. What could be happening is that the brain is conducting an internal simulation as a way to understand the metaphor, and that’s why the regions associated with touch get involved. This also demonstrates how complex processes involving symbols, such as appreciating a painting or understanding a metaphor, do not depend just on evolutionarily new parts of the brain, but also on adaptations of older parts of the brain."

Sathian’s future plans include asking whether similar relationships exist for other senses, such as vision. The researchers also plan to probe whether magnetic stimulation of the brain in regions associated with sensory experience can interfere with understanding metaphors.

The research was supported by the National Institutes of Health and the National Science Foundation.

Source: ScienceDaily

Article Date: 04 Feb 2012 - 10:00 PST

The February edition of Neurosurgery reports that animal experiments in brain-injured rats have shown that stem cells injected via the carotid artery travel directly to the brain, greatly enhancing functional recovery. The study demonstrates, according to leading researcher Dr Toshiya Osanai, of Hokkaido University Graduate School of Medicine in Sapporo, Japan, that the carotid artery injection technique could, together with some form of in-vivo optical imaging to track the stem cells after transplantation, potentially be part of a new approach for stem cell transplantation in human brain trauma injuries (TBI).

Dr. Osanai and team assessed a new “intra-arterial” technique of stem cell transplantation in rats, with the aim of delivering the stem cells directly to the brain without having to go through the general circulation. They induced TBI in the animals before injecting stem cells into the carotid artery seven days later.

The stem cells were obtained from the rats’ bone marrow and were labeled with “quantum dots” prior to being injected. Quantom dots are a biocompatible, fluorescent semiconductor created with nanotechnology that emit near-infrared light with much longer wavelengths that penetrate bone and skin, enabling a non-invasive method of monitoring the stem cells for a period of four weeks following transplantation.

This in vivo optical imaging technique enabled the scientists to observe that the injected stem cells entered the brain on the first attempt, without entering the general circulation. They observed that the stem cells started migrating from the capillaries into the injured part of the brain within three hours.

At week 4, the researchers noted that the rats in the stem cell transplant group achieved a substantial recovery of motor function, compared with the untreated animals that had no signs of recovery.

The team learnt, after examining the treated brains, that the stem cells had transformed into different brain cell types and aided in healing the injured brain area.

Over the last few years, the potential of stem cell therapy for curing and treating illnesses and conditions has been growing rapidly. Below is a list of some of its possible uses.

(Photo by: Mikael Häggström)

Developing stem cell therapy for brain injury in human patients

Stem cells represent a potential, new important method of treatment for those who suffered brain injuries, TBI and stroke. But even though bone marrow stem cells, similar to the ones used in the new study, are a promising source of donor cells, many questions remain open regarding the optimal timing, dose and route of stem cell delivery.

In the new animal study, the rats were injected with the stem cells one week after TBI. This is a “clinically relevant” time, given that this is the minimum time it takes to develop stem cells from bone marrow.

Transplanting the stem cells into the carotid artery is a fairly simple procedure that delivers the cells directly to the brain.

The experiments have also provided key evidence that stem cell treatment can promote healing after TBI with a substantial recovery of function.

Dr. Osanai and team write that by using in vivo optical imaging:

"The present study was the first to successfully track donor cells that were intra-arterially transplanted into the brain of living animals over four weeks."

A similar form of imaging technology could also prove beneficial for monitoring the effects of stem cell transplantation in humans, although the tracking will pose challenges, due to the human skull and scalp being much thicker than in rats.

The researchers conclude:

"Further studies are warranted to apply in vivo optical imaging clinically.”

Written by Petra Rattue

Source: Medical News Today

ScienceDaily (Feb. 3, 2012) — One of the big mysteries in biology is why cells age. Now scientists at the Salk Institute for Biological Studies report that they have discovered a weakness in a component of brain cells that may explain how the aging process occurs in the brain.

This microscope image shows extremely long-lived proteins, or ELLPs, glowing green on the outside of the nucleus of a rat brain cell. DNA inside the nucleus is pictured in blue. The Salk scientists discovered that the ELLPs, which form channels through the wall of the nucleus, lasted for more than a year without being replaced. Deterioration of these proteins may allow toxins to enter the nucleus, resulting in cellular aging. (Credit: Courtesy of Brandon Toyama, Salk Institute for Biological Studies)

The scientists discovered that certain proteins, called extremely long-lived proteins (ELLPs), which are found on the surface of the nucleus of neurons, have a remarkably long lifespan.

While the lifespan of most proteins totals two days or less, the Salk Institute researchers identified ELLPs in the rat brain that were as old as the organism, a finding they reported February 3 in Science.

The Salk scientists are the first to discover an essential intracellular machine whose components include proteins of this age. Their results suggest the proteins last an entire lifetime, without being replaced.

ELLPs make up the transport channels on the surface of the nucleus; gates that control what materials enter and exit. Their long lifespan might be an advantage if not for the wear-and-tear that these proteins experience over time. Unlike other proteins in the body, ELLPs are not replaced when they incur aberrant chemical modifications and other damage.

Damage to the ELLPs weakens the ability of the three-dimensional transport channels that are composed of these proteins to safeguard the cell’s nucleus from toxins, says Martin Hetzer, a professor in Salk’s Molecular and Cell Biology Laboratory, who headed the research. These toxins may alter the cell’s DNA and thereby the activity of genes, resulting in cellular aging.

Funded by the Ellison Medical Foundation and the Glenn Foundation for Medical Research, Hetzer’s research group is the only lab in the world that is investigating the role of these transport channels, called the nuclear pore complex (NPC), in the aging process.

Previous studies have revealed that alterations in gene expression underlie the aging process. But, until the Hetzer lab’s discovery that mammals’ NPCs possess an Achilles’ heel that allows DNA-damaging toxins to enter the nucleus, the scientific community has had few solid clues about how these gene alterations occur.

"The fundamental defining feature of aging is an overall decline in the functional capacity of various organs such as the heart and the brain," says Hetzer. "This decline results from deterioration of the homeostasis, or internal stability, within the constituent cells of those organs. Recent research in several laboratories has linked breakdown of protein homeostasis to declining cell function."

The results that Hetzer and his team just report suggest that declining neuron function may originate in ELLPs that deteriorate as a result of damage over time.

"Most cells, but not neurons, combat functional deterioration of their protein components through the process of protein turnover, in which the potentially impaired parts of the proteins are replaced with new functional copies," says Hetzer.

"Our results also suggest that nuclear pore deterioration might be a general aging mechanism leading to age-related defects in nuclear function, such as the loss of youthful gene expression programs," he adds.

The findings may prove relevant to understanding the molecular origins of aging and such neurodegenerative disorders as Alzheimer’s disease and Parkinson’s disease.

In previous studies, Hetzer and his team discovered large filaments in the nuclei of neurons of old mice and rats, whose origins they traced to the cytoplasm. Such filaments have been linked to various neurological disorders including Parkinson’s disease. Whether the misplaced molecules are a cause, or a result, of the disease has not yet been determined.

Also in previous studies, Hetzer and his team documented age-dependent declines in the functioning of NPCs in the neurons of healthy aging rats, which are laboratory models of human biology.

Hetzer’s team includes his colleagues at the Salk Institute as well as John Yates III, a professor in the Department of Chemical Physiology of The Scripps Research Institute.

When Hetzer decided three years ago to investigate whether the NPC plays a role in initiating or contributing to the onset of aging and certain neurodegenerative diseases, some members of the scientific community warned him that such a study was too bold and would be difficult and expensive to conduct. But Hetzer was determined despite the warnings.

Source: ScienceDaily

by Jon Cohen on 1 February 2012, 6:00 PM

Synaptic division. Compared with chimpanzees, human children children slowly wire their brains. Credit: Fotosearch