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Kicking Cancer and other Things turned 10 today!
Kicking Cancer and other Things turned 10 today!
(Image caption: Induced pluripotent stem cells (iPSCs) derived from patients with frontotemporal dementia were genetically corrected and converted to cortical neurons. The green staining indicates the cortical marker CTIP2, the red stain is the neuronal marker TUJ1, and the blue stains the nuclei of the cells. Credit: Susanna Raitano/Stem Cell Reports 2014)
Patient stem cells used to make dementia-in-a-dish; help identify new treatment strategy
Belgian researchers have identified a new strategy for treating an inherited form of dementia after attempting to turn stem cells derived from patients into the neurons most affected by the disease. In patient-derived stem cells carrying a mutation predisposing them to frontotemporal dementia, which accounts for about half of dementia cases before the age of 60, the scientists found a targetable defect that prevents normal neurodevelopment. These stem cells partially return to normal when the defect is corrected.
The study appears in the December 31st issue of Stem Cell Reports, the official journal of the International Society of Stem Cell Research published by Cell Press.
"Use of induced pluripotent stem cell (iPSC) technology"—which involves taking skin cells from patients and reprogramming them into embryonic-like stem cells capable of turning into other specific cell types relevant for studying a particular disease—"makes it possible to model dementias that affect people later in life," says senior study author Catherine Verfaillie of KU Leuven.
Frontotemporal disorders are the result of damage to neurons in parts of the brain called the frontal and temporal lobes, gradually leading to behavioral symptoms or language and emotional disorders. Mutations in a gene called progranulin (GRN) are commonly associated with frontotemporal dementia, but GRN mutations in mice do not mimic all the features of the human disorder, which has limited progress in the development of effective treatments.
"iPSC models can now be used to better understand dementia, and in particular frontotemporal dementia, and might lead to the development of drugs that can curtail or slow down the degeneration of cortical neurons," Verfaillie says.
Verfaillie and Philip Van Damme of the Leuven Research Institute for Neuroscience and Disease explore this approach in the Stem Cell Reports study by creating iPSCs from three patients carrying a GRN mutation. These immature cells were impaired at turning into mature, specialized cells called cortical neurons—the most affected cell type in frontotemporal dementia.
One of the top defective pathways in the iPSCs was the Wnt signaling pathway, which plays an important role in neuronal development. However, genetic correction or treatment with a compound that inhibits the Wnt signaling pathway restored the ability of the iPSCs to turn into cortical neurons. Taken together, the findings demonstrate that the GRN mutation causes the defect in cortical neuron formation by altering the Wnt signaling pathway.
"Our findings suggest that signaling events required for neurodevelopment may also play major roles in neurodegeneration," Van Damme says. "Targeting such pathways, as for instance the Wnt pathway presented in this study, may result in the creation of novel therapeutic approaches for frontotemporal dementia."
The researchers will now work to better understand what goes wrong in GRN-mutated cells, as well as identify precise molecular targets that could then be used for drug screens.
First Real-time MRI-guided Brain Surgery for Parkinson’s in Southern California
Neurosurgeons at UC San Diego Health System are the first in Southern California to implant a deep brain stimulator (DBS) in a patient with Parkinson’s disease using real-time 3-D magnetic resonance image (MRI) guidance.
Parkinson’s disease is a progressive disorder of the nervous system that affects movement. Symptoms include shaking, slowness of movement and difficulty walking. These unpredictable movements are caused by abnormal nerve cell activity in the brain. DBS therapy, like a heart pacemaker, transmits electrical signals to help restore normal activity.
Traditionally, DBS surgery is conducted while the patient is awake, and under pain management. This approach allows surgeons to continuously monitor the patient’s brain function and to ensure accurate placement of the device.
“Now, for some patients, this surgery can be performed in the MRI suite under general anesthesia so that a patient can sleep during the placement of the DBS electrodes,” David Barba, MD, director of functional neurosurgery, UC San Diego Health System. “Within a few days of DBS therapy, many patients can resume life’s everyday activities.”
“Placing a DBS device while a patient is awake can be exhausting for the patient due to the length of the procedure and the need to perform neurologic testing in the operating room,” added Clark Chen, MD, PhD, director of stereotactic and radiosurgery, UC San Diego Health System. “Fortunately, with continuous real-time MRI monitoring, we can now place the electrode in a safe location that provides maximal neurological benefit while the patient is under the comfort of general anesthesia.”
Bob S. Carter, MD, PhD, professor and chief of neurosurgery, and co-director of the UC San Diego Neurological Institute said the collaborative endeavor introduces a new technology strategy to improve the care of patients with Parkinson’s and other diseases.
“Our capacity to perform these procedures will be further enhanced in the new A. Vassiliadis Family Hospital for Advanced Surgery at Jacobs Medical Center which opens in 2016,” said Carter.
DBS can also be used to treat other movement disorders, including dystonia, essential tremor and obsessive compulsive disorder. It is in clinical trial testing as treatment for depression.
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A gene implicated in human speech disorders and epilepsy is also required for vocalization and synapse formation in mice, researchers discover.
Gene Found to Foster Synapse Formation in the Brain
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Learning dialects shapes brain areas that process spoken language
Using advanced imaging to visualize brain areas used for understanding language in native Japanese speakers, a new study from the RIKEN Brain Science Institute finds that the pitch-accent in words pronounced in standard Japanese activates different brain hemispheres depending on whether the listener speaks standard Japanese or one of the regional dialects.
In the study published in the journal Brain and Language, Drs. Yutaka Sato, Reiko Mazuka and their colleagues examined if speakers of a non-standard dialect used the same brain areas while listening to spoken words as native speakers of the standard dialect or as someone who acquired a second language later in life.
When we hear language our brain dissects the sounds to extract meaning. However, two people who speak the same language may have trouble understanding each other due to regional accents, such as Australian and American English. In some languages, such as Japanese, these regional differences are more pronounced than an accent and are called dialects.
Unlike different languages that may have major differences in grammar and vocabulary, the dialects of a language usually differ at the level of sounds and pronunciation. In Japan, in addition to the standard Japanese dialect, which uses a pitch-accent to distinguish identical words with different meanings, there are other regional dialects that do not.
Similar to the way that a stress in an English word can change its meaning, such as “pro’duce” and “produ’ce”, identical words in the standard Japanese language have different meanings depending on the pitch-accent. The syllables of a word can have either a high or a low pitch and the combination of pitch-accents for a particular word imparts it with different meanings.
The experimental task was designed to test the participants’ responses when they distinguish three types of word pairs: (1) words such as /ame’/ (candy) versus /kame/ (jar) that differ in one sound, (2) words such as /ame’/ (candy) versus /a’me/ (rain) that differ in their pitch accent, and (3) words such as ‘ame’ (candy in declarative intonation) and /ame?/ (candy in a question intonation).
RIKEN neuroscientists used Near Infrared Spectroscopy (NIRS) to examine whether the two brain hemispheres are activated differently in response to pitch changes embedded in a pair of words in standard and accent-less dialect speakers. This non-invasive way to visualize brain activity is based on the fact that when a brain area is active, blood supply increases locally in that area and this increase can be detected with an infrared laser.
It is known that pitch changes activate both hemispheres, whereas word meaning is preferentially associated with the left-hemisphere. When the participants heard the word pair that differed in pitch-accent, /ame’/ (candy) vs /a’me/ (rain), the left hemisphere was predominantly activated in standard dialect speakers, whereas in accent-less dialect speakers did not show the left-dominant activation. Thus, standard Japanese speakers use the pitch-accent to understand the word meaning. However, accent-less dialect speakers process pitch changes similar to individuals who learn a second language later in life.
The results are surprising because both groups are native Japanese speakers who are familiar with the standard dialect. “Our study reveals that an individual’s language experience at a young age can shape the way languages are processed in the brain,” comments Dr. Sato. “Sufficient exposure to a language at a young age may change the processing of a second language so that it is the same as that of the native language.”
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Behold what a football field at Bristol Motor Speedway will look like (Photo) That's one big stadium for football. Bristol Motor Speedway and Tennessee and Virginia Tech officially announced the creation of "The Battle at Bristol" between the two schools at the track on September 10, 2016. That's just two weeks after Bristol's … Continue reading →