Biology subjects

Hanse, E.

Publications and source records attributed to Hanse, E..

3 recordsLinked to original sources

bioRxiv2025

Slow Wave Sleep Reduces CSF Concentrations of Beta-amyloid and Tau: A Randomized Crossover Study in Healthy Adults

BackgroundSlow-wave sleep has been proposed to facilitate the removal of proteins, implicated in neurodegeneration, from the brain. While mechanistic evidence from animal models is accumulating, direct human data on how slow-wave sleep shapes cerebrospinal fluid (CSF) proteostasis remain limited, constraining our understanding of physiological resilience to neurodegenerative disease. MethodsTwelve healthy adults (aged 20-40 years) underwent CSF sampling following three controlled sleep conditions in a randomized crossover design; (1) one night of sleep followed by afternoon CSF sampling, (2) one night of sleep followed by morning CSF sampling, and (3) one night of total sleep deprivation followed by morning CSF sampling. Sleep and wakefulness were verified using polysomnography and actigraphy, with >4-week washout periods between conditions. Measured CSF biomarkers included Alzheimers disease-related proteins: beta-amyloid isoforms (A{beta}38, A{beta}40, and A{beta}42), total and phosphorylated tau, glial fibrillary acidic protein (GFAP), and neurofilament light, as well as orexin, albumin (also measured in serum), and osmolality. Differences between conditions were assessed using Friedman tests with Dunns post hoc correction. ResultsCSF levels of A{beta} and tau tended to be consistently lower after sleep compared with both afternoon sampling and post-sleep deprivation. Concurrently, CSF albumin levels increased after sleep, while neurofilament light and GFAP remained unchanged. Orexin levels rose markedly during sleep deprivation but showed no circadian variation. ConclusionsThese findings support a model in which slow wave sleep enhances CSF turnover, reducing concentrations of specific proteins, including A{beta} and tau. Understanding how sleep regulates the homeostasis of neurodegeneration-related proteins may inform strategies to mitigate disease progression.

neuroscience↗

bioRxiv2025

Non-Physiological Potassium Concentrations in Commercial Culture Media Trigger Acute Epileptiform Activity in Human iPSC-Derived Neurons

Neuronal in vitro cultures are pivotal for studying brain electrophysiological function and dysfunction. Neuronal activity and communication are regulated by extracellular ion concentrations. Therefore, cell culture medium ion concentrations should ideally mimic those of cerebrospinal fluid (CSF) - considered as the milieu for brain cells in vivo. In this study, we demonstrate that commonly used cell culture media, including Neurobasal (+/- A), Neurobasal Plus, and BrainPhys media, do not accurately replicate human CSF ion concentrations. Using human iPSC-derived neuronal networks on microelectrode arrays, we show that the abnormally high potassium concentrations present in all tested cell culture media induce acute epileptiform activity, similar to that elicited by the convulsive drug 4- aminopyridine. These findings raise a critical question: How can human in vitro neuronal activity be defined as physiological and reliably distinguished from pathophysiological activity, if the routinely used ion concentrations in in vitro experiments are causing aberrant neuronal activity? SummaryThe neuronal activity in neuronal in vitro culture relies on extracellular ion concentrations, which should mimic cerebrospinal fluid (CSF). This study shows that common cell culture media and widely used artificial CSF composition in neuroscience research fail to replicate CSF ion levels, causing non-physiological and rather pathological neuronal activity.

neuroscience↗

bioRxiv2024

Hebbian induction adds AMPA-labile signaling units to CA3-CA1 synapses in the developing hippocampus

In the 2nd postnatal week hippocampus, Hebbian-induced long-term potentiation (LTP) of AMPA receptor-mediated transmission in CA3-CA1 synapses is not a genuine potentiation. Instead, it is a de-depression (unsilencing) and temporary stabilization of postsynaptically AMPA-labile synapses silenced by a prior test pulse (0.03 - 0.2 Hz) stimulation. In addition to such an LTP, Hebbian induction at these synapses also results in a labile potentiation that becomes depotentiated by test pulse stimulation, thus appearing as an Hebbian-induced short- term potentiation (STP). Although the induction of this labile potentiation was blocked in the combined presence of N-methyl-D-aspartate (NMDA) and metabotropic glutamate (mGlu) receptor antagonists, the depotentiation was not affected by these drugs. The labile potentiation was not associated with a change in paired-pulse ratio and was, after a depotentiation, fully re-established by a 20 min interruption of test pulse stimulation. These properties are shared with the silencing of previously non-stimulated (naive) AMPA-labile synapses by such test pulse stimulation. However, the depotentiation following an Hebbian induction is not a re-silencing of naive AMPA labile synapses since there is no correlation between the magnitudes of depotentiation and preceding silencing of naive synapses. The present results suggest that Hebbian induction at these neonatal CA3-CA1 synapses, in addition to unsilencing and temporary stabilization of AMPA-labile transmission, creates a labile potentiation based on the insertion/activation of an additional AMPA-labile signaling unit to a pre-existing synapse.

neuroscience↗