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Category: neuroscience – Page 12

Enhanced Selenium Supplement Extends Lifespan and Delays Multi‐Organs Aging by Regulating the Sik1 Pathway Through Maintaining Calcium Homeostasis

In healthy aging strategies, nutritional supplements synergize with optimized dietary and lifestyle interventions by modulating aging-related molecular pathways.[ 8, 9 ] Notably, NMN exerts multi-organ anti-aging effects by elevating NAD+ levels to activate the SIRT1 pathway, thereby significantly enhancing mitochondrial function while reducing oxidative stress and DNA damage.[ 10 ] Similarly, curcumin delays aging and related diseases through pleiotropic mechanisms involving oxidative stress regulation, anti-inflammatory actions, telomere maintenance, and sirtuin protein modulation.[ 11 ] However, practical applications face significant challenges: bioactive compounds like resveratrol and curcumin suffer from limited bioavailability due to poor aqueous solubility and first-pass metabolism, while excessive supplementation of antioxidants such as vitamins C/E may disrupt reactive oxygen species (ROS) signaling homeostasis, potentially inducing cellular toxicity or even increasing hemorrhagic risk.[ 12-14 ] Future development of anti-aging supplements should focus on: 1) innovative formulation strategies to enhance bioavailability; 2) optimized dosing regimens to minimize toxicity; and 3) long-term clinical studies to validate efficacy.

Selenium, an essential trace element with diverse biological activities, plays a critical role in healthy aging.[ 15-17 ] ≈1 billion people worldwide are affected by selenium deficiency, which is closely linked to neurological disorders, cardiovascular abnormalities, malignancies, and immune dysfunction.[ 18-20 ] Substantial evidence supports the anti-aging effects of selenium through multiple mechanisms: 1) Selenomethionine (SeMet) effectively suppresses Fe2+/H2O2- or Aβ-induced free radical generation, demonstrating therapeutic potential for Alzheimer’s disease characterized by oxidative stress;[ 21 ] 2) Selenium supplementation elevates serum GPx3 levels, a selenoprotein predominantly localized in the basement membrane of renal proximal tubules, modulating mitochondrial quality control pathways to mitigate heavy metal-induced renal aging;[ 22 ] and 3) Our recent findings reveal that selenium supplementation significantly attenuates age-related muscle atrophy by preserving redox homeostasis and regulating muscle protein metabolism.[ 23 ] Recent clinical trials in patients with advanced non-small cell lung cancer (NSCLC) demonstrated that oral administration of selenium nanoparticles (SeNPs) as a dietary supplement (200 µg day−1) in combination with Bev+AP chemotherapy significantly enhanced therapeutic outcomes compared to chemotherapy alone. The SeNPs combination group showed remarkable tumor regression, with progression disease rates decreasing dramatically from 50% to 0% and partial response rates increasing to 83.3%, along with significantly improved objective response rate and disease control rate.[ 24 ] Importantly, this regimen maintained excellent safety profiles without triggering fluctuations in pro-inflammatory or immunosuppressive cytokines. These compelling findings not only establish SeNPs as a safe and effective adjuvant therapy for advanced NSCLC but also provide valuable clinical translation data for nano-selenium formulations in oncology. Despite selenium’s proven benefits in reducing oxidative damage, maintaining genomic stability, and delaying telomere shortening, its narrow therapeutic window, limited bioavailability, and specific mechanisms in multi-organ protection during natural aging require further investigation.

Nanodelivery carriers have emerged as a next-generation platform for gene and drug delivery, offering tunable physicochemical properties such as size, composition, and surface modifications.[ 25 ] Our team has developed organically-bridged mesoporous silica nanoparticles (MSNs) by incorporating functional diselenide bonds into the silica framework at the molecular level, addressing the critical challenge of poor biodegradability in conventional silica materials.[ 26 ] This nanocarrier exhibits unique dual redox-responsive properties, allowing for more precise maintenance of redox homeostasis compared to traditional antioxidants, aligning with the core goal of preserving organismal homeostasis in anti-aging research. Building on this breakthrough, a comprehensive research framework was established: first, this study constructed a natural aging mouse model with MSNs, disulfide-bridged MSNs (SMSNs), commercially available SeMet as controls and then compared the effects of diselenide-bridged MSNs (SeMSNs) on lifespan extension, frailty delay, and multi-organ anti-aging. Next, key pathways and targets were identified through multi-organ transcriptome sequencing, followed by in-depth mechanistic studies. Finally, clinical translation was integrated by analyzing the correlation between serum selenium levels and aging biomarkers in the elderly, and validating the clinical effects of SeMSNs using primary adipose precursor cells (APCs) models. This systematic approach provides a solid theoretical foundation and clinical evidence for the application of nano-selenium in anti-aging research.

No current theory of consciousness is scientific

A letter by distinguished scientists directed at Integrated Information Theory sought to discredit a leading theory of consciousness as pseudoscience. That, argues Erik Hoel, was a mistake.

Hoel contends that as no theory of consciousness is currently empirically testable, it’s impossible for any of these theories to be scientific.

Hoel is a neuroscientist, neurophilosopher, and fiction writer. He’s been a close collaborator of Giulio Tononi, and a Forbes 30 under 30 in science.

“Consciousness, according to IIT, might be more widespread than we think, but it is neither universal nor arbitrary,” writes Hoel.

Tap the link to read more now.

Predicting Return Home After Moderate-to-Severe Traumatic Brain Injury

Background and ObjectivesDays alive and at home (DAH) is a validated outcome measure that captures health care transitions between time spent at home vs various nonhome care settings, offering a more nuanced patient-centered understanding of recovery. We…

MIT’s new brain tool could finally explain consciousness

Although the technology has been around for several years, it has not yet become a standard tool in neuroscience research. Now, two researchers at MIT are preparing new experiments using the technique and have published a paper that serves as a detailed guide, or “roadmap,” for applying it to the study of consciousness.

“Transcranial focused ultrasound will let you stimulate different parts of the brain in healthy subjects, in ways you just couldn’t before,” says Daniel Freeman, an MIT researcher and co-author of the paper. “This is a tool that’s not just useful for medicine or even basic science, but could also help address the hard problem of consciousness. It can probe where in the brain are the neural circuits that generate a sense of pain, a sense of vision, or even something as complex as human thought.”

Unlike other brain stimulation methods, transcranial focused ultrasound does not require surgery. It can reach deeper areas of the brain with greater precision than techniques such as transcranial magnetic or electrical stimulation.

Episode 2 — The Prospect of Immortality & Human Cryopreservation

Host: Kyle O’Brien — https://twitter.com/analog_kyle.

Guest: Emil Kendziorra — https://twitter.com/emilkendziorra.
Founder of @TomorrowBio.

Theme || the prospect of immortality & human cryopreservation.

Is Death just a Technical Problem we haven’t solved yet?

In this episode of State Change, Kyle O’Brien sits down with Emil Kendziorra, founder of Tomorrow Bio, to explore the science, ethics, and future of cryopreservation — the process that may one day allow humans (and even pets) to be revived centuries from now.

We talk about the brain, identity, consciousness, why people fear death, and what it means to rewrite the social contract when life extension becomes real.

Continue reading “Episode 2 — The Prospect of Immortality & Human Cryopreservation” | >

The layer 6b theory of attention

(A) Neuromodulatory projections of the ascending arousal system project divergent axons across the cortex, including to L6b, providing state-dependent signals. Likewise, higher-order cortical axons project to multiple cortical regions, including L6b, providing top-down volitional signals. L6b integrates the convergent input from these two pathways and directs its output to CTC loops with fast and focused activation.

(B) L6b is depolarized by arousal-promoting neuromodulators (left), and we hypothesize that the addition of higher-order cortical feedback strongly activates L6b (right). Thus, the role of neuromodulation is to bring L6b close to the activation threshold across the cortex so that specific L6b circuits can be more easily recruited by specific top-down cortical input. ACh, acetylcholine; 5HT, serotonin; DA, dopamine; NA, noradrenaline; HIS, histamine.

Ultrastructural and Histological Cryopreservation of Mammalian Brains by Vitrification

Studies of whole brain cryopreservation are rare but are potentially important for a variety of applications. It has been demonstrated that ultrastructure in whole rabbit and pig brains can be cryopreserved by vitrification (ice-free cryopreservation) after prior aldehyde fixation, but fixation limits the range of studies that can be done by neurobiologists, including studies that depend upon general molecular integrity, signal transduction, macromolecular synthesis, and other physiological processes. We now show that whole brain ultrastructure can be preserved by vitrification without prior aldehyde fixation. Rabbit brain perfusion with the M22 vitrification solution followed by vitrification, warming, and fixation showed an absence of visible ice damage and overall structural preservation, but osmotic brain shrinkage sufficient to distort and obscure neuroanatomical detail. Neuroanatomical preservation in the presence of M22 was also investigated in human cerebral cortical biopsies taken after whole brain perfusion with M22. These biopsies did not form ice upon cooling or warming, and high power electron microscopy showed dehydrated and electron-dense but predominantly intact cells, neuropil, and synapses with no signs of ice crystal damage, and partial dilution of these samples restored normal cortical pyramidal cell shapes. To further evaluate ultrastructural preservation within the severely dehydrated brain, rabbit brains were perfused with M22 and then partially washed free of M22 before fixation. Perfusion dilution of the brain to 3-5M M22 resulted in brain re-expansion and the re-appearance of well-defined neuroanatomical features, but rehydration of the brain to 1M M22 resulted in ultrastructural damage suggestive of preventable osmotic injury caused by incomplete removal of M22. We conclude that both animal and human brains can be cryopreserved by vitrification with predominant retention of ultrastructural integrity without the need for prior aldehyde fixation. This observation has direct relevance to the feasibility of human cryopreservation, for which direct evidence has been lacking until this report. It also provides a starting point for perfecting brain cryopreservation, which may be necessary for lengthy space travel and could allow future medical time travel.

The authors have declared no competing interest.

The surprising way the brain’s dopamine-rich reward center adapts as a romance matures

A new study published in the journal Social Cognitive and Affective Neuroscience provides evidence that the human brain processes romantic partners differently than close friends, specifically within the reward system. The research suggests that while the brain creates a unique neural signature for a partner early in a relationship, this distinction tends to fade as the bond matures. These findings offer insight into how the biological drivers of romantic love may evolve from passion to companionship over time.

Relationships involve complex psychological states that differentiate a committed partner from a platonic friend. Scientists have sought to map these differences in the brain to understand the biological foundations of human bonding. Much of this research focuses on the nucleus accumbens. This small region deep within the brain, which relies heavily on the neurotransmitter dopamine, plays a central role in processing rewards and motivation.

Evidence from animal studies indicates that the nucleus accumbens is essential for forming pair bonds. Research on monogamous prairie voles shows that neurochemical signaling in this area drives the preference for a specific partner. The brain appears to undergo plastic changes that reinforce the bond.

Mutation in one Parkinson’s protein eases cellular traffic jams caused by another

A hallmark of Parkinson’s disease is the buildup of Lewy bodies—misfolded clumps of the protein known as alpha-synuclein. Long before Lewy bodies form, alpha-synuclein can interfere with neurons’ ability to transport proteins and other cargo along their axons to the synapses. When present at high levels, alpha-synuclein binds too tightly to structures inside the axon, creating the cellular equivalent of traffic jams. These disruptions may even help set the stage for the later accumulation of Lewy bodies in the brain.

Now, University at Buffalo researchers have identified a way to reduce these traffic jams and restore flow—by altering how alpha-synuclein interacts with another Parkinson’s-related protein known as leucine-rich repeat kinase 2 (LRRK2).

In a study published last month, the researchers increased levels of specific mutant forms of LRRK2 in fruit fly larvae. They found that one mutation had a downstream effect on alpha-synuclein, limiting its ability to bind to cargo and disrupt axonal transport. The research is published in the journal Frontiers in Molecular Neuroscience.

A new way to communicate with neurons using focused ultrasound stimulation

I still vividly remember the first time we observed neurons responding not to audible sound, but to concentrated, precisely calibrated ultrasonic pulses. On the screen in front of us, calcium signals from brain cells began to rise and fall in little waves. It was less about forcing the brain to adapt and more about listening to the brain and responding subtly.

Understanding how neurons interact and how neurological conditions like Parkinson’s disease affect this communication has been the focus of my study for many years. Calcium, a small ion that functions as a potent messenger inside cells, is at the center of this communication.

Neurons struggle to survive, connect, and operate correctly when calcium transmission is disrupted. Our team began to wonder if we might safely modify this fundamental signaling function without requiring invasive operations or drugs.

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