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Recapping Neuroscience 2014
12-11-2014
by Randall C Willis  |  Email the author
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Capitalizing on Brain Power
 
Tens of thousands of scientists from around the world flocked to Washington, D.C., in November to attend Neuroscience 2014, sharing insights and experiences on topics ranging from neurodegenerative disorders to addiction to sensory systems both human and technological. Below is just a sample of some of the research that was presented.
 
 
Nanoparticles for Parkinson’s
 
In earlier work using a MPTP-induced mouse model of Parkinson’s disease (PD), researchers at Virginia College of Osteopathic Medicine had demonstrated that cerium oxide nanoparticles (CeONPs) could protect mice from dopaminergic loss when given before the MPTP challenge. As they presented last week in Washington, these same particles—known to protect cells from oxidative stress and mitochondrial damage—may also work to reverse PD damage once it has begun.
 
After inducing PD in the mouse model with several injections of MPTP, the researchers then injected a single dose of CeONP. A week later, mice were sacrificed and brains were examined for dopamine content in the striatum, the number of dopaminergic neurons and lipid peroxidation levels.
 
They found that CeONP introduction not only maintained striatal dopamine at 50 percent of normal levels, it also preserved dopaminergic neuron counts by about 85 percent of controls and reduced oxidative stress. All of this offers hope for future PD treatment.
 
“Our research demonstrates for the first time that cerium oxide nanoparticles have the potential of slowing down, halting or even reversing the progression of Parkinson’s disease after the disease has developed,” said study lead author Beverly Rzigalinski in announcing the study.
 
 
Just getting started in Parkinson’s
 
One frustrating challenge for people with Parkinson’s disease (PD) is simply initiating movement, and it can seem as though they are stuck. Research from Lisbon’s Champalimaud Centre for the Unknown suggests that this may indeed be the case and that motion is more fluid once people get past this inertial block.
 
Using optogenetics—a method that effectively adds an on-off switch to cellular activation—the researchers examined the role of SNC dopaminergic neurons in the initiation of self-paced movement in mice. They found that inhibiting SNC dopaminergic neurons caused mice to spend more time immobile, but if the mouse was already moving when they flipped the switch, mobility was not impeded until the first time the mouse stopped.
 
They also found, in very preliminary results, that the opposite was also true. A very brief activation of SNC dopaminergic neurons was sufficient to promote movement in immobile mice. Thus, it would appear that these neurons are critical to movement initiation but not maintenance of ongoing movement.
 
“It’s long been known that the destruction of dopamine-producing neurons is a hallmark of Parkinson’s disease, but until now, the connection between the loss of those neurons and the ability to initiate movement, a symptom of Parkinson’s, wasn’t clear,” stated Joaquim Alves da Silva, lead author of the study. “Our research indicates that dopamine neurons are critical to initiate movement.”
 
 
What an oligomeric web (Part One)
 
The aggregation of the protein tau is a pathological hallmark of many neurodegenerative conditions including Alzheimer’s disease (AD) and traumatic brain injury (TBI). Traditionally, chaotic tau tangles had been thought to promote these diseases, but a growing body of evidence is suggesting that this may not be the case; rather, the culprit may be more organized tau oligomers.
 
Using immunoprecipitation, researchers from the University of Texas, Galveston, isolated tau oligomers from the brains of AD, fluid-percussion-injured rat and blast-injured mouse brains, which they characterized biochemically and morphologically using atomic fluorescence microscopy. They then injected the oligomers into the brains of mice overexpressing human tau protein (Htau mice).
 
They confirmed that TBI did produce tau oligomers reminiscent of those found in AD brains and that these oligomers were able to induce cognitive deficiencies when introduced into Htau mice.
 
“Our findings add to the growing evidence that tau oligomers—not tau protein in general—are responsible for the development of neurodegenerative diseases such as Alzheimer’s and for damage associated with traumatic brain injury,” stated study lead author Julia Gerson. “These tau anomalies may be a viable target for drug development in TBI and in prevention of neurodegenerative diseases.”
 
 
What an oligomeric web (Part Two)
 
In a completely separate presentation, Diederik Moechars of Janssen R&D in Beerse, Belgium, continued the conversation about tau aggregates, describing his group’s efforts to study the way tau propagated through the brain. The researchers relied on synthetic fibrils made of recombinant tau that they injected into young mice overexpressing mutant human tau protein.
 
The synthetic fibrils not only caused rapid production of inclusions that looked like neurofibrillary tangles (NFTs) but that these inclusions spread from the injection site into surrounding brain regions in a dose- and time-dependent manner. Interestingly, the researchers noted that the spread patterns varied depending on where the initial injection was made, e.g., hippocampus vs. cortex, and that the spread was reflective of functional connectivities.
 
Diederik suggests that injected tau may be taken up by the processes of normal neurons where it corrupts endogenous tau. The corrupted tau then transports along the processes to be released and taken up by other neurons in something akin to a cascade.
 
The researchers are using these learnings, he reports, to create a model of human AD that may be more faithful than conventional transgenic mouse models that simply overexpress mutant genes that develop aggregates.
 
 

 
Five Factors Regulating Neuroimmune Signals:  New Data from the 2014 Society for Neuroscience Meeting
Contributed by EMD Millipore
 
Neuroimmunology was a dominant theme throughout November’s Society for Neuroscience Annual Meeting. Immune signaling to the brain, mediated by microglia, is an established component of many pathologies such as obesity, Parkinson’s disease, schizophrenia, multiple sclerosis and traumatic brain injury. This year’s meeting also highlighted the role of other factors, such as age, diet, maternal immune activation, circadian cycles and social stress that modulate neuroimmune signals.
 
Age: Researchers from Emory University reported that immune cells from older Parkinson’s disease (PD)  patients showed higher levels of LRRK2 than young non-PD or older non-PD subjects.
 
Steven Maier’s team at the University of Colorado, Boulder, is renowned for their studies on immune-to-brain signaling. Among their many presentations was one nanosymposium talk revealing the details of synaptic function changes with respect to aging and infection. Aging sensitized brain immune response to infection (mediated by IL- 1beta), disrupting memory formation and increasing cognitive dysfunction.
 
The Godbout lab at Ohio State reported that aging causes decreased IL-10 response in astrocytes, resulting in dysregulation of microglia and associated behavioral changes.
 
DietIt is well-known that high-fat food intake affects neuroimmune signaling and chronic system inflammation. Some of the molecular mechanisms by which food can change specific behaviors are being discovered. Rats on a high-fat diet have been shown to exhibit decreased anxiety (less defecation in an anxiety-inducing open space). Researchers from the Leibowitz lab at Rockefeller University reported that a specific chemokine, CXCL12, may be mediating this effect at low doses.
 
Diet alters the gut microbiome, long known to be pivotal in regulating the gut-brain axis and mediated by immune signaling. The meeting featured many new studies revealing specific molecules that carried specific signals. These included the neuropeptides vasopressin and oxytocin.
 
Maternal Immune ActivationIt has been widely observed in rodent studies that challenges to the maternal immune system during brain development in utero have been found to shape behavior. Bauman and colleagues at the University of California, Davis presented new PET imaging data from the first nonhuman primate model of maternal immune activation, observing that offspring of mothers receiving immune challenge showed schizophrenia-like symptoms.
 
Social StressResearchers at the NIH compared acute and chronic social stress, and their respective effects on the morphology of microglia, the immune-responsive cells of the brain. This type of study was made possible by the generation of GFP-reporter mice with constitutively fluorescent microglia.
 
Circadian ClockMore work from the Maier lab revealed that the immune system was regulated by the circadian clock. Specifically, sickness behavior, such as anhedonia, weight loss and reduced social exploration, differed when rodents’ immune systems were challenged in the middle of light or dark cycles. Cytokines, such as IL-1beta, TNFalpha and IL-6, varied along with circadian clock proteins like Per1 and Per2.
 
Another study from Rockefeller University reported at the meeting implicated dendritic cells in the circadian response to infection.
 
Code: 12111498

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