"Building functional models of the complex cellular networks such as those found in the brain is probably one of the highest challenges you could aspire to,
there is a new kid on the block Alzheimer's disease is associated with the appearance of characteristic neurotoxic protein aggregates in various regions in the brain.
In collaboration with neurobiologist Dr. Hélène Marie based at the IPMC-CNRS in Valbonne (France) and with the local colleagues from the Technical University of Munich (TUM) in the Synergy Excellence Cluster (Professor Arthur Konnerth
the LMU researchers have studied also the effects of the eta-amyloid on nerve-cell function in the brain.
Beta-amyloid is known to make nerve cells hyperactive, and now it turns out that the eta-amyloid antagonizes this effect."
and might therefore compromise brain function, "says Haass. He therefore suggests that investigators need to be on the look out for any signs of unanticipated side-effects in the current clinical trials a
akin to the misfolded proteins involved in incurable progressive brain diseases such Creutzfeldt-jakob disease (CJD), according to two new research papers led by scientists at UC San francisco. The findings suggest new approaches to developing treatments for MSA,
since work at the National institutes of health in the 1960s showed that human brain tissue infected with CJD could transmit neurodegeneration to chimpanzees.
insoluble plaques throughout the brain that kill off cells and result in the typical"spongy"appearance of CJD-affected brains.
and an international team of colleagues report that a misfolded version of a protein called alpha-synuclein seems to act in a similar way to transmit MSA from diseased human brain tissue to mice and to human cell cultures.
as well as loss of bladder control, blood-pressure regulation and other functions governed by the autonomic nervous system. Unlike Parkinson's patients, who often live 10 to 20 years after their diagnosis,
or deep brain stimulation used for Parkinson's symptoms. As in Parkinson's disease, neurodegeneration in MSA is accompanied by a buildup of clumps of alpha-synuclein protein within brain cells.
Both MSA and PD can arise sporadically in families with no history of the disease,
showing that samples of brain tissue from two human MSA patients were able to transmit the disease to a mouse model for Parkinson's disease,
the Massachusetts Alzheimer's disease Research center in Boston, the Parkinson's UK Brain Bank at Imperial College London,
and the Sydney Brain Bank in Australia. The results were the same: When exposed to human MSA tissue, the mice developed neurodegeneration.
In addition, the team found that the brains of infected mice contained abnormally high levels of insoluble human alpha-synuclein,
and that infected mouse brain tissue could itself spread the disease to other mice. The discovery that alpha-synuclein prions can transmit MSA raises a public health concern about treatments
and research that involve contact with brain tissue from neurodegeneration patients, because standard disinfection techniques that kill microbes do not eliminate the Prp prions that cause CJD.
which is treated often with deep-brain stimulation. The disease could potentially be transmitted to other patients
if deep-brain stimulation equipment is reused.""You can't kill a protein, "Giles said.""And it can stick tightly to stainless steel,
People are living longer and likely getting more brain surgeries. There could be undiagnosed neurodegenerative diseases that
Arrayin 2004, professor Petter Strømme examined a child with congenital cataract, growth delay and symptoms from the brain, the peripheral nervous system,
The levels of these variants are of great importance for cells in the nervous system. Measurements of cells from the patients showed that their levels diverged distinctly,
Ilia Karatsoreos, an assistant professor in WSU's Department of Integrative Physiology and Neuroscience, shifted mice from their usual cycle of sleeping
"The work by Karatsoreos and his colleagues--published in the journal Brain, Behavior and Immunity--is a rare look into the circadian process,
a brain-driven clock that controls the rhythms of various biological processes, from digestion to blood pressure, heart rate to waking and sleeping.
and the pattern of electrical activity in their brains related to restorative sleep was reduced greatly d
"because no one who is paralyzed completely has walked independently in the absence of the robotic device and electrical stimulation of the spinal cord.)
and suffered a spinal cord injury that left him paralyzed from the waist down. At UCLA, Pollock made substantial progress after receiving a few weeks of physical training without spinal stimulation
and quality of life,"said V. Reggie Edgerton, senior author of the research and a UCLA distinguished professor of integrative biology and physiology, neurobiology and neurosurgery.
and the nervous system shuts down, "Edgerton said. The data showed that Pollock was actively flexing his left knee and raising his left leg and that during and after the electrical stimulation,
"We need to expand the clinical toolbox available for people with spinal cord injury and other diseases."
"Given the complexities of a spinal cord injury, there will be no one-size-fits-all cure but rather a combination of different interventions to achieve functional recovery."
"What we are seeing right now in the field of spinal cord research is a surge of momentum with new directions
"This is a great example of a therapeutic approach that combines two very different modalities--neuromodulation
"Neurorecovery Technologies, a medical technology company Edgerton founded, designs and develops devices that help restore movement in patients with paralysis. The company provided the device used to stimulate the spinal cord in combination with the Ekso in this research.
he now believes it is possible to significantly improve quality of life for patients with severe spinal cord injuries,
but neuroscientists at UC Santa barbara may have uncovered a mechanism by which onset can be delayed by as much as 10 years.
"said co-author Kenneth S. Kosik, co-director of UCSB's Neuroscience Research Institute and a professor in the Department of Molecular, Cellular and Developmental biology."
See-through brains ready for study Researchers at the RIKEN Brain science Institute in Japan have developed a new technique for creating transparent tissue that can be used to illuminate 3d brain anatomy at very high resolutions.
Published in Nature Neuroscience, the work showcases the new technology and its practical importance in clinical science by showing how it has given new insights into Alzheimer's disease plaques."
called Scales, is a real and practical way to see through brain and body tissue.""In recent years, generating see-through tissue--a process called optical clearing--has become a goal for many researchers in life sciences because of its potential to reveal complex structural details of our bodies, organs,
"By combining sorbitol in the right proportion with urea, we could create transparent brains with minimal tissue damage,
"The new technique creates transparent brain samples that can be stored in Scales solution for more than a year without damage.
and brains are firm enough to permit the micron-thick slicing necessary for more detailed analyses."
the researchers put the technique to practical use by visualizing in 3d the mysterious"diffuse"plaques seen in the postmortem brains of Alzheimer's disease patients that are typically undetectable using 2d imaging.
but showed extensive association with microglia--mobile cells that surround and protect neurons. Another example of Scales's practical application came from examining the 3d positions of active microglial cells and amyloid beta plaques.
While some scientists suggest that active microglial cells are located near plaques, a detailed 3d reconstruction and analysis using Scales clearing showed that association with active microglial cells occurs early in plaque development,
and pinpointing structural changes that characterize other brain diseases
#Biodiesel made easier, cleaner with waste-recycling catalyst Researchers at Cardiff University have devised a way of increasing the yield of biodiesel by using the waste left over from its production process.
like the eyes, kidney, brain and bone. But this new research found that in certain patients with AML--a type of blood cancer that affects white blood cells
#Loss of cellular energy leads to neuronal dysfunction in neurodegenerative disease model A new study from the Gladstone Institutes shows for the first time that impairments in mitochondria--the brain's cellular power plants--can deplete cellular energy levels
or assays, were not available to measure ATP (the energy unit of the cell that is generated by mitochondria) in individual neurons.
the scientists created novel assays to more accurately measure the brain's energy production. Using a model of Leigh's disease,
the researchers tested energy levels in neurons using the new assays. They found that the genetic mutation associated with Leigh's disease compromised ATP levels,
which would be toxic to neurons, "says first author Divya Pathak, Phd, a postdoctoral fellow in the Gladstone Institute of Neurological disease."
"Applying their new assay in healthy neurons, the researchers also determined the energy threshold needed to support synaptic vesicle cycling--the process by
which brain cells release neurotransmitters to communicate with each other. The scientists blocked glycolysis, another way that cells make ATP,
so that the cells had to rely solely on their mitochondria for energy. This allowed the researchers to more accurately assess the contribution of mitochondrial ATP to different steps in the cycle,
From this exploration, the scientists revealed that bringing the vesicles back up into the cell after they have released their neurotransmitters is the most energy-demanding process.
which neurotransmitters are shipped--with and without mitochondria. Remarkably, there was no difference in energy levels between the two,
and both types of boutons had sufficient ATP to support synaptic vesicle cycling. From this, the scientists concluded that under normal conditions,
including brain tissue from surgical steel. Cleaning instruments between patients is critical to avoid transmission of agents leading to conditions such as Creutzfeldt-jakob disease.
has identified a protein that regulates the growth of neurons by transporting key metabolic enzymes to the tips of neural cells.
Neurotransmitters--chemicals used by brain cells to communicate--are essential for brain function. In particular, acetylcholine, which was the first neurotransmitter to be discovered,
is involved in cognition and motor functions. Although much is known about the synthesis and secretion of this critical neurotransmitter, the spatial and temporal regulation of acetylcholine synthesis remains unclear.
Specifically, how key metabolic enzymes such as ATP citrate lyase (ACL) and choline acetyltransferase (Chat) find their way to the right region of the neuron is largely unknown.
To unravel this puzzle, the NUS team, led by Associate professor Boon Chuan Low and his postdoctoral fellow Dr Jichao Sun,
from the Department of Biological sciences and Mechanobiology Institute at NUS, collaborated with researchers from the Yong Loo Lin School of medicine at NUS
and the University of Michigan (U-M). They identified and characterised a protein that transports the enzyme ACL to the tips of neurons,
where it subsequently recruits another enzyme Chat for acetylcholine synthesis. This ACL-transporting protein, called BNIP-H, was linked first to Cayman ataxia,
a rare genetic disorder affecting a region of the brain involved in motor control and which leads to difficulty in coordinating complex movements,
-H in cell lines, primary neuron cultures and zebrafish using molecular genetics, protein biochemistry and high speed imaging.
marking ACL for transport by the enzyme kinesin-1 to the neuron terminals. Once there
triggering the targeted release of acetylcholine. Using mass spectrometry, the researchers showed that expressing more BNIP-H in cultured cells could increase acetylcholine secretion while knockdown of BNIP-H reduced acetylcholine secretion.
The BNIP-H-induced increase of acetylcholine in turn launches a positive feedback loop involving the MAPK/ERK signalling pathway that ultimately promotes growth of neurites,
which are projections from neurons.""BNIP-H defines the precise localisation, duration and strength of acetylcholine signalling that determines the growth of neurons
and the coordination of body movements,"explained Assoc Prof Low, the corresponding author of the paper.
The study also provides the first experimental data solidifying the link between dysfunctional cholinergic (acetylcholine) secretion and Cayman ataxia.
The researchers showed that a BNIP-H mutant associated with Cayman ataxia caused defects in the transport of the ACL enzyme.
suggesting that the loss of acetylcholine secretion resulting from BNIP-H mutation could explain some of the symptoms of Cayman ataxia.
Their work also serves as a foundation for further studies into acetylcholine-related diseases, and may lead to new treatments that involve BNIP-H."Our findings could provide new direction to better understand causes of cholinergic-related diseases, such as Alzheimer's disease, Down's syndrome, ataxia and schizophrenia.
has identified a protein that regulates the growth of neurons by transporting key metabolic enzymes to the tips of neural cells.
Neurotransmitters--chemicals used by brain cells to communicate--are essential for brain function. In particular, acetylcholine, which was the first neurotransmitter to be discovered,
is involved in cognition and motor functions. Although much is known about the synthesis and secretion of this critical neurotransmitter, the spatial and temporal regulation of acetylcholine synthesis remains unclear.
Specifically, how key metabolic enzymes such as ATP citrate lyase (ACL) and choline acetyltransferase (Chat) find their way to the right region of the neuron is largely unknown.
To unravel this puzzle, the NUS team, led by Associate professor Boon Chuan Low and his postdoctoral fellow Dr Jichao Sun,
from the Department of Biological sciences and Mechanobiology Institute at NUS, collaborated with researchers from the Yong Loo Lin School of medicine at NUS
and the University of Michigan (U-M). They identified and characterised a protein that transports the enzyme ACL to the tips of neurons,
where it subsequently recruits another enzyme Chat for acetylcholine synthesis. This ACL-transporting protein, called BNIP-H, was linked first to Cayman ataxia,
a rare genetic disorder affecting a region of the brain involved in motor control and which leads to difficulty in coordinating complex movements,
-H in cell lines, primary neuron cultures and zebrafish using molecular genetics, protein biochemistry and high speed imaging.
marking ACL for transport by the enzyme kinesin-1 to the neuron terminals. Once there
triggering the targeted release of acetylcholine. Using mass spectrometry, the researchers showed that expressing more BNIP-H in cultured cells could increase acetylcholine secretion while knockdown of BNIP-H reduced acetylcholine secretion.
The BNIP-H-induced increase of acetylcholine in turn launches a positive feedback loop involving the MAPK/ERK signalling pathway that ultimately promotes growth of neurites,
which are projections from neurons.""BNIP-H defines the precise localisation, duration and strength of acetylcholine signalling that determines the growth of neurons
and the coordination of body movements,"explained Assoc Prof Low, the corresponding author of the paper.
The study also provides the first experimental data solidifying the link between dysfunctional cholinergic (acetylcholine) secretion and Cayman ataxia.
The researchers showed that a BNIP-H mutant associated with Cayman ataxia caused defects in the transport of the ACL enzyme.
suggesting that the loss of acetylcholine secretion resulting from BNIP-H mutation could explain some of the symptoms of Cayman ataxia.
Their work also serves as a foundation for further studies into acetylcholine-related diseases, and may lead to new treatments that involve BNIP-H."Our findings could provide new direction to better understand causes of cholinergic-related diseases, such as Alzheimer's disease, Down's syndrome, ataxia and schizophrenia.
a connection to nerve endings or the central nervous system, a beating heart, and so on, "they wrote. Ren's lab reported the mechanics of making a new transparent and stretchable electric material,
"We could pull 12 metastatic cells out of the brain and tell you what is special about those 12 cells.
whether lymph, liver, lung or brain. In contrast, early-stage metastases and cancer cells traveling through the blood expressed genes typically active in mammary stem cells and quite distinct from primary tumor cells.
#Team links two human brains for question -and-answer experiment Researchers used a brain-to-brain interface they developed to allow pairs of participants to play a'20 question'style game by transmitting signals from one brain to another over the Internet.
Their experiment is thought to be the first to demonstrate that two brains can be linked directly to allow someone to accurately guess what is on another person's mind.
Sci-fi? Mind-reading superpowers? Not quite.""This is the most complex brain-to-brain experiment, I think,
that's been done to date in humans, "said lead author Andrea Stocco, an assistant professor of psychology and a researcher at UW's Institute for Learning & Brain sciences."
"It uses conscious experiences through signals that are experienced visually, and it requires two people to collaborate,
or"respondent,"wears a cap connected to an electroencephalography (EEG) machine that records electrical brain activity.
But only a"yes"answer generates a response intense enough to stimulate the visual cortex and cause the inquirer to see a flash of light known as a"phosphene."
The researchers took steps to ensure participants couldn't use clues other than direct brain communication to complete the game.
"They have to interpret something they're seeing with their brains, "said co-author Chantel Prat, a faculty member at the Institute for Learning & Brain sciences and a UW associate professor of psychology."
"It's not something they've ever seen before.""Errors can also result from respondents not knowing the answers to questions or focusing on both answers,
or by the brain signal transmission being interrupted by hardware problems.""While the flashing lights are signals that we're putting into the brain,
those parts of the brain are doing a million other things at any given time too,
"Prat said. The study builds on the UW team's initial experiment in 2013, when it was the first to demonstrate a direct brain-to-brain connection between humans.
Other scientists have connected the brains of rats and monkeys, and transmitted brain signals from a human to a rat, using electrodes inserted into animals'brains.
In the 2013 experiment, the UW team used noninvasive technology to send a person's brain signals over the Internet to control the hand motions of another person.
The first experiment evolved out of research by co-author Rajesh Rao, a UW professor of computer science and engineering,
on brain-computer interfaces that enable people to activate devices with their minds. In 2011, Rao began collaborating with Stocco
and Prat to determine how to link two human brains together. In 2014, the researchers received a $1 million grant from the W. M. Keck Foundation that allowed them to broaden their experiments to decode more complex interactions and brain processes.
They are now exploring the possibility of"brain tutoring, "transferring signals directly from healthy brains to ones that are impaired developmentally
or impacted by external factors such as a stroke or accident, or simply to transfer knowledge from teacher to pupil.
The team is also working on transmitting brain states--for example, sending signals from an alert person to a sleepy one,
or from a focused student to one who has attention deficit hyperactivity disorder, or ADHD."
"Imagine having someone with ADHD and a neurotypical student, "Prat said.""When the non-ADHD student is paying attention,
the ADHD student's brain gets put into a state of greater attention automatically.""Many technological advancements over the past century, from the telegraph to the Internet, were created to facilitate communication between people.
and other animals to take information out of our brains and communicate it to other animals in the forms of behavior, speech and so on,
We can only communicate part of whatever our brain processes.""What we are doing is kind of reversing the process a step at a time by opening up this box
and taking signals from the brain and with minimal translation, putting them back in another person's brain,
Other co-authors are UW computer science and neurobiology undergraduate student Darby Losey, UW bioengineering doctoral student Jeneva Cronin, UW bioengineering doctoral student Joseph Wu,
and Justin Abernethy, a research assistant at the UW Institute for Learning & Brain sciences s
In a study published in Cell, Feng Zhang and his colleagues at the Broad Institute of MIT and Harvard and the Mcgovern Institute for Brain Research at MIT,
Will brain palpation soon be possible? If there is one technique used by the physician to explore the human body during every medical examination
however, the brain cannot be palpated without using a highly invasive procedure (craniotomy, or opening the skull),
Ultimately, it could be used in the early diagnosis of brain tumours or Alzheimer's disease. This work is published in PNAS.
However, this method cannot be applied to the brain, which, doubly protected by the cranium and cerebrospinal fluid, is difficult for externally applied waves to access.
It is therefore impossible to directly or indirectly palpate the brain, something that greatly complicates the work of neurosurgeons.
On the other hand, the brain is the seat of natural vibrations created by the blood pulsating in the arteries and the circulating cerebrospinal fluid.
There remained a significant unprecedented challenge: how to capture this complex field of natural shear waves,
have succeeded in detecting natural shear waves in the brain using computational techniques borrowed from seismologists and known as"noise correlation."
"They were thus able to build images of the brain's elasticity.""If this method can be developed for clinical use,
since making the brain vibrate is quite painful at the moment. Of course, this method will be complementary to those that already exist,
"Alzheimer's disease, epilepsy, multiple sclerosis and hydrocephalus involve changes in the stiffness of the brain tissues. This new technique allows their detection,
and could be used to avoid brain biopsies.""This method for palpating the brain could have other areas of application,
such as for analysing the development of neurodegenerative processes, the impact of a lesion from a trauma or tumour, response to treatment, etc e
Also on the horizon is research using scorpion venom to target brain tumours with MRI scanning g
lead study author and professor and chair of the Department of Pharmacology and Experimental Neuroscience at Nebraska,
Gelbard, director of UR's Center for Neural development and Disease, developed URMC-099 to treat HIV-associated neurocognitive disorders or HAND,
Both cardiac cells in the heart and neurons in the brain communicate by electrical signals,
which so far has been used mainly in brain science. Dr Gil Bub, from Oxford university explained:''When there is scar tissue in the heart or fibrosis,
and shape of such excitation waves would mean unprecedented direct control of organ-level function, in the heart or brain,
including those in our own brains and hearts s
#Some patients in a vegetative state retain awareness, despite being unable to move New insight into a vital cerebral pathway has explained how some patients in a vegetative state are aware
identify structural damage between the thalamus and primary motor cortex as the obstacle between covert awareness and intentional movement.
""In highlighting damage to the pathways that physically connect the thalamus, one of the hubs of consciousness if you will,
and the motor cortex, which drives our voluntary muscular activity, as the reason behind the dissociation we have provided an important explanation."
was observed in a case study at the imaging centre at the Brain and Mind Institute, at Western University, Canada.
"while their brain activity was measured. Additionally the researchers assessed the integrity of the structural pathways that were revealed as essential for successful motor execution (those connecting the thalamus with the motor cortex.
Dr Fernández-Espejo added,"The ultimate aim is to use this information in targeted therapies that can drastically improve the quality of life of patients.
play an important role in a number of diseases that affect the nervous system, including Parkinson's.
which stops nerve cells from working. A gene called HIFALPHA was found to regulate the nerve signals from damaged mitochondria and,
the early failure of nerve cells caused by mitochondrial damage was prevented. An identical effect was observed in flies with Leigh syndrome,
Dr Joseph Bateman from the Institute of Psychiatry, Psychology & Neuroscience (Ioppn) at King's college London, said:'
'The biggest surprise from our work is damaged that mitochondria produce a signal that actively prevents nerve cells from working properly.
Thanks to this study we now have a much better understanding of how nerve cells function,
'Understanding how subtle changes in our genes may trigger brain cell death is one of the most promising avenues for the development of new treatments for Parkinson's.'
and Ear/Harvard Medical school and Boston University have shown successfully neuroprotection in a Parkinson's mouse model using new techniques to deliver drugs across the naturally impenetrable blood-brain barrier.
lend hope to patients around the world with neurological conditions that are difficult to treat due to a barrier mechanism that prevents approximately 98 percent of drugs from reaching the brain and central nervous system."
"We are developing a platform that may eventually be used to deliver a variety of drugs to the brain,
seizure disorders and many other conditions affecting the brain and nervous system down the road.""Using nasal mucosal grafting,
researchers delivered glial derived neurotrophic factor (GDNF), a therapeutic protein in testing for treating Parkinson's disease, to the brains of mice.
They showed through behavioral and histological data capture that their delivery method was equivalent to direct injection of GDNF--the current gold standard for delivering this drug in Parkinson's disease despite its traumatic nature and high complication rates--in diffusing drugs to the brain.
The researchers chose to test their delivery method with GDNF because the therapy has been shown to delay and even reverse disease progression of Parkinson's disease in preclinical models.
"Brain diseases are notoriously difficult to treat due to the natural protections the body builds against intrusion,
"Nasal mucosal grafting is a technique regularly used in the ENT field to reconstruct the barrier around the brain after surgery to the skull base.
ENT surgeons commonly use endoscopic approaches to remove brain tumors through the nose by making a window through the blood-brain barrier to access the brain.
with the nasal lining protecting the brain from infection just as the blood brain barrier has done. Dr. Bleier saw an opportunity to apply these techniques to the widespread clinical dilemma of delivering drugs across the barrier to the brain and central nervous system.
By functionally replacing a section of the blood-brain barrier with nasal mucosa, which is more than 1, 000 times more permeable than the native barrier,
surgeons may create a"screen door"to allow for drug delivery to the brain and central nervous system. The technique has the potential to benefit a large population of patients with neurodegenerative disorders,
where there remains a specific unmet need for blood-brain penetrating therapeutic delivery strategies.""We see this expanding beyond Parkinson's disease,
as there are multiple diseases of the brain that do not have good therapeutic options, "Dr. Bleier said."
"It is a platform that opens doors for new discovery and could enable drug development for an underserved population
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