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Category: neuroscience

Summary: Tufts researchers have developed neurotransmitter-lipid hybrids that help transport therapeutic drugs and gene editing proteins across the blood-brain barrier in mice.

Source: Tufts University

Biomedical engineers at the Tufts University School of Engineering have developed tiny lipid-based nanoparticles that incorporate neurotranmitters to help carry drugs, large molecules, and even gene editing proteins across the blood-brain barrier and into the brain in mice. The innovation, published today in Science Advances, could overcome many of the current limitations encountered in delivering therapeutics into the central nervous system, and opens up the possibility of using a wide range of therapeutics that would otherwise not have access to the brain.

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The clues have been mounting for a while. First, scientists discovered patients who had recovered from infection with Covid-19, but mysteriously didn’t have any antibodies against it. Next it emerged that this might be the case for a significant number of people. Then came the finding that many of those who do develop antibodies seem to lose them again after just a few months.

In short, though antibodies have proved invaluable for tracking the spread of the pandemic, they might not have the leading role in immunity that we once thought. If we are going to acquire long-term protection, it looks increasingly like it might have to come from somewhere else.

But while the world has been preoccupied with antibodies, researchers have started to realise that there might be another form of immunity – one which, in some cases, has been lurking undetected in the body for years. An enigmatic type of white blood cell is gaining prominence. And though it hasn’t previously featured heavily in the public consciousness, it may well prove to be crucial in our fight against Covid-19. This could be the T cell’s big moment.

While the latest research suggests that antibodies against Covid-19 could be lost in just three months, a new hope has appeared on the horizon: the enigmatic T cell.

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Summary: Depending on the network state, certain neurons in the primary somatosensory cortex can be more or less excitable, which shapes stimulus processing in the brain.

Source: Max Planck Institute

Rustling leaves, light rain at the window, a quietly ticking clock – muffled sounds, just above the threshold of hearing. One moment we perceive them, the next we don’t, even if we, or the sounds, don’t seem to change. Many studies have shown that we never process an incoming stimulus, be it a sound, an image, or a touch, in the same way. This is true, even if the stimulus is exactly the same. This occurs because the impact a stimulus makes, on the brain regions that process it, depends on the momentary state of the networks those brain regions belong to. However, the factors that influence and underlie the constantly fluctuating momentary state of the networks and whether these states are random or follow a rhythm, was previously unknown.

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Utilizing neurotransmitters as a passport into the brain:

Safe and efficient delivery of blood-brain barrier (BBB)–impermeable cargos into the brain through intravenous injection remains a challenge. Here, we developed a previously unknown class of neurotransmitter–derived lipidoids (NT-lipidoids) as simple and effective carriers for enhanced brain delivery of several BBB-impermeable cargos. Doping the NT-lipidoids into BBB-impermeable lipid nanoparticles (LNPs) gave the LNPs the ability to cross the BBB. Using this brain delivery platform, we successfully delivered amphotericin B (AmB), antisense oligonucleotides (ASOs) against tau, and genome-editing fusion protein (−27)GFP-Cre recombinase into the mouse brain via systemic intravenous administration. We demonstrated that the NT-lipidoid formulation not only facilitates cargo crossing of the BBB, but also delivery of the cargo into neuronal cells for functional gene silencing or gene recombination. This class of brain delivery lipid formulations holds great potential in the treatment of central nervous system diseases or as a tool to study the brain function.

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Objective To determine whether training with a brain–computer interface (BCI) to control an image of a phantom hand, which moves based on cortical currents estimated from magnetoencephalographic signals, reduces phantom limb pain.

Methods Twelve patients with chronic phantom limb pain of the upper limb due to amputation or brachial plexus root avulsion participated in a randomized single-blinded crossover trial. Patients were trained to move the virtual hand image controlled by the BCI with a real decoder, which was constructed to classify intact hand movements from motor cortical currents, by moving their phantom hands for 3 days (“real training”). Pain was evaluated using a visual analogue scale (VAS) before and after training, and at follow-up for an additional 16 days. As a control, patients engaged in the training with the same hand image controlled by randomly changing values (“random training”). The 2 trainings were randomly assigned to the patients. This trial is registered at UMIN-CTR (UMIN000013608).

Results VAS at day 4 was significantly reduced from the baseline after real training (mean [SD], 45.3 [24.2]–30.9 [20.6], 1/100 mm; p = 0.009 < 0.025), but not after random training (p = 0.047 0.025). Compared to VAS at day 1, VAS at days 4 and 8 was significantly reduced by 32% and 36%, respectively, after real training and was significantly lower than VAS after random training (p < 0.01).

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When our neurons—the principle cells of the brain—die, so do we.

Most neurons are created during and have no “backup” after birth. Researchers have generally believed that their survival is determined nearly extrinsically, or by outside forces, such as the tissues and that neurons supply with .

A research team led by Sika Zheng, a biomedical scientist at the University of California, Riverside, has challenged this notion and reports the continuous survival of neurons is also intrinsically programmed during development.

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Even healthy brains become less efficient as they age, but they do so at different rates for different tasks in different people. Understanding what contributes to this decline, and the ways in which that decline varies, can provide significant insight into the function of the brain.

In a new study, researchers at The University of Texas at Dallas documented how some parts of the brain perform differently over time in response to various kinds of visual input.

A team from the Center for Vital Longevity (CVL) analyzed a phenomenon called neural dedifferentiation, in which regions of the brain that normally are specialized to perform distinct tasks become less selective in their responses to stimulus types.

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The thalamus is a “Grand Central Station” for sensory information coming to our brains. Almost every sight, sound, taste and touch we perceive travels to our brain’s cortex via the thalamus. It is theorized that the thalamus plays a major role in consciousness itself. Not only does sensory information pass through the thalamus, it is also processed and transformed by the thalamus so our cortex can better understand and interpret these signals from the world around us.

One powerful type of transformation comes from interactions between excitatory neurons that carry data to the neocortex and inhibitory neurons of the thalamic reticular nucleus, or TRN, that regulate flow of that data. Although the TRN has long been recognized as important, much less has been known about what kinds of cells are in the TRN, how they are organized and how they function.

Now a paper published in the journal Nature addresses those questions. Researchers led by corresponding author Scott Cruikshank, Ph.D., and co-authors Rosa I. Martinez-Garcia, Ph.D., Bettina Voelcker, Ph.D., and Barry Connors, Ph.D., show that the somatosensory part of the TRN is divided into two functionally distinct sub-circuits. Each has its own types of genetically defined neurons that are topographically segregated, are physiologically distinct and connect reciprocally with independent thalamocortical nuclei via dynamically divergent synapses.

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