Summary: Study reveals a novel mechanism in locus coeruleus neurons caused by the loss of the GPT2 mitochondrial enzyme that is implicated in the development and progression of neurodegenerative diseases.
Source: Brown University.
The locus coeruleus is among the first brain regions to degenerate in Alzheimer’s and Parkinson’s disease, physicians and scientists have known. But why this area is so vulnerable is less understood.
Summary: A 20-minute session of non-invasive brain stimulation over four days helps to improve both working and long-term memory in those aged 65 and older.
Source: Boston University.
According to the Alzheimer’s Association, an estimated 6.5 million Americans aged 65 and older are living with Alzheimer’s in 2022. That figure is predicted to nearly double by 2050.
Electrical activity in neurons is highly energy demanding and accompanied by rises in cytosolic Ca2+. Cytosolic Ca2+, in turn, secures energy supply by pushing mitochondrial metabolism either through augmented NADH transfer into mitochondria via the malate aspartate shuttle (MAS) or via direct activation of dehydrogenases of the TCA cycle after passing into the matrix through the mitochondrial Ca2+ uniporter (MCU). Another Ca2+-sensitive booster of mitochondrial ATP synthesis is the glycerol-3-phosphate shuttle (G3PS) whose role in neuronal energy supply has remained elusive. Essential components of G3PS are expressed in hippocampal neurons. Single neuron metabolic measurements in primary hippocampal cultures derived from rat pups of either sex reveal only moderate, if any, constitutive activity of G3PS. However, during electrical activity neurons fully rely on G3PS when MAS and MCU are unavailable. Under these conditions, G3PS is required for appropriate action potential firing. Accordingly, G3PS safeguards metabolic flexibility of neurons to cope with energy demands of electrical signaling.
SIGNIFICANCE STATEMENT:
Ca2+ ions are known to provide a link between the energy-demanding electrical activity and an adequate ATP supply in neurons. To do so, Ca2+ acts both, from outside and inside of the mitochondrial inner membrane. Neuronal function critically depend on this regulation and its defects are often found in various neurological disorders. Although interest in neuronal metabolism increases, many aspects thereof have remained unresolved. In particular, a Ca2+-sensitive NADH shuttling system, the glycerol-3-phosphate shuttle, has been largely ignored with respect to its function in neurons. Our results demonstrate that this shuttle is functional in hippocampal neurons and safeguards ATP supply and appropriate action potential firing when malate aspartate shuttle and mitochondrial Ca2+ uniporter are unavailable, thereby ensuring neuronal metabolic flexibility.
Lecture from the mini-series “Cosmology & Quantum Foundations” from the “Philosophy of Cosmology” project. A University of Oxford and Cambridge Collaboration.
This session explores the nature of consciousness, including efforts to define and measure it. What systems have subjective experience? What do we mean when we refer to various types of consciousness? How simple, and how sophisticated, can consciousness in principle be? Can we define necessary conditions for a physical system to be conscious? Sufficient conditions?
Posted in neuroscience
Summary: A new language-switching experiment revealed traditional categorization of brain areas may not be sufficient. Researchers set their sights on the caudal inferior parietal cortex to better understand functional categorization in the brain.
Source: Leiden University.
Based on the results of a language-switching experiment, Ph.D. candidate Fatemeh (Simeen) Tabassi Mofrad MA and Professor Niels Schiller have discovered that the traditional categorization of brain areas is not sufficient.
The trial was only on 8 people, but it appears to have worked well across the board.
Published in GeroScience, a groundbreaking study from the renowned Conboy lab has confirmed that plasma dilution leads to systemic rejuvenation against multiple proteomic aspects of aging in human beings.
This paper takes the view that much of aging is driven by systemic molecular excess. Signaling molecules, antibodies, and toxins, which gradually accumulate out of control, cause cells to exhibit the gene expression that characterizes older cells.
While the bloodstreams of old and young mice have been joined in previous experiments with substantial effects [1], this heterochronic parabiosis approach is neither feasible nor necessary for human beings. Instead, this paper focuses on therapeutic plasma exchange (TPE), a procedure that simply replaces blood plasma with saline solution and albumin. This procedure has already been used to dilute pathogenic, toxic compounds [2], the systemic problems associated with autoimmune and neurological disorders, including Alzheimer’s [3], and even the lingering aftereffects of viral infection [4].
For trained mathematical brains, the infinite is if anything even more bamboozling. Mathematicians have known for well over a century now that infinity isn’t just one thing, it is infinitely many. There is an unending tower of ever greater infinities stretching up all the way to… well, whatever you’d like to call it.
That isn’t even the worst of it. Although the existence of this tower of infinities is a logical consequence of mathematics as we know it, that same mathematics is powerless to describe it completely. Chip away at the plaster to reveal the structure underneath and you see that crucial load-bearing beams are missing in the lower levels, suggesting that the foundations of mathematics itself are unstable.
Mathematicians have long argued about how best to shore the infinite tower up. Some say we should simply leave well alone and hope for the best. Others have proposed fixes, variously deemed too costly, unlikely to work or not in keeping with the original style. No one has yet made anything like a breakthrough. Except, perhaps, until now. After decades of apparent stalemate, serious progress seems to have been made on the baffling question that lies at the heart of it all: a nearly 150-year-old unproven conjecture known as the continuum hypothesis.
In a study published in Cell Reports, we present a novel algorithm for the digital generation of neuronal morphologies, based on the topology of their branching structure. This algorithm generates neurons that are statistically similar to the biological neurons, in terms of morphological properties, electrical responses and the connectivity of the networks they form.
This study represents a major milestone for the Blue Brain Project and for the future of computational neuroscience. The topological neuron synthesis enables the generation of millions of unique neuronal shapes from different cell types. This process will allow us to reconstruct brain regions with detailed and unique neuronal morphologies at each cell position.
The topological representation of neurons facilitates the generation of neurons that approximate morphologies that are structurally altered compared to healthy neuronal morphologies. These structural alterations of neurons are disrupting the brain systems and are contributing factors to brain diseases. The topological synthesis can be used to study the differences between healthy and diseased states of different brain regions and specifically, what structural alterations of neurons are causing important problems to the networks they form.
