Biology subjects

Bergman, L.

Publications and source records attributed to Bergman, L..

5 recordsLinked to original sources

bioRxiv2025

Plasma, not extracellular vesicles, disrupts the blood-brain barrier in eclampsia.

BackgroundEclampsia is a severe complication of preeclampsia involving blood-brain barrier (BBB) disruption. While small extracellular vesicles (sEVs) contribute to endothelial dysfunction in preeclampsia, their role in eclampsia remains unclear. Magnesium sulfate (MgSO), the standard treatment, may mitigate BBB injury. We examined the effects of plasma and plasma-derived sEVs from women with eclampsia on BBB integrity and the potential modulatory role of MgSO. MethodsPlasma and plasma-sEVs were isolated from women with normotensive pregnancies (n=18), preeclampsia (n=19), preeclampsia with organ complications (n=17), and eclampsia (n=20). An in vitro BBB model based on the culture of human brain endothelial cells was used to evaluate electrical resistance (TEER), Dextran 70 kDa permeability, and cytoskeletal alterations in the presence of womens plasmas or plasma-sEVs. The uptake of fluorescently labeled sEVs in the absence or pretreatment (-3 h) with MgSO, and sEVs cargo of relevant proteins involved in BBB regulation, were analyzed. ResultsPlasma from women with eclampsia disrupted the BBB, with marked reductions in TEER and increased permeability compared to normotensive controls, preeclampsia, and preeclampsia with organ complications. In contrast, plasma-sEVs of women with eclampsia caused less BBB impairment than plasma-sEVs from normotensive controls or preeclampsia, correlating with reduced sEVs uptake by brain endothelial cells. Lower levels of eNOS and TNF- in eclampsia-derived sEVs compared to normotensive controls were founnd. MgSO treatment further diminished sEVs uptake. ConclusionsPlasma, rather than sEVs, appears to drive BBB disruption in eclampsia. MgSO may influence these effects by reducing sEVs uptake and altering their protein cargo.

physiology↗

bioRxiv2020

Anesthetic Drug Concentration Rather Than Abrupt Behavioral Unresponsiveness Linearly Degrades Responses in the Rat Primary Auditory Cortex

Despite extensive knowledge of its molecular and cellular effects, how anesthesia affects sensory processing remains poorly understood. In particular, it remains unclear whether anesthesia modestly or robustly degrades activity in primary sensory regions, and whether such changes are linked to anesthesia drug concentration vs. behavioral unresponsiveness, since these are typically confounded. Here, we employed slow gradual intravenous propofol anesthesia induction together with auditory stimulation and intermittent assessment of behavioral responsiveness while recording epidural EEG, and neuronal spiking activity in the primary auditory cortex (PAC) of eight rats. We found that all main components of neuronal activity including spontaneous firing rates, onset response magnitudes, onset response latencies, post-onset neuronal silence duration, and late-locking to 40Hz click-trains, gradually deteriorated in a dose- dependent manner with increasing anesthesia levels without showing abrupt changes around loss of righting reflex or other time-points. Thus, the dominant factor affecting PAC responses is the anesthesia drug concentration rather than any sudden, dichotomous behavioral state changes. Our findings explain a wide array of seemingly conflicting results in the literature that, depending on the precise definition of wakefulness (vigilant vs. drowsy) and anesthesia (light vs. deep/surgical), report a spectrum of effects in primary regions ranging from minimal to dramatic differences.

neuroscience↗

bioRxiv2020

AMPlify: attentive deep learning model for discovery of novel antimicrobial peptides effective against WHO priority pathogens

Antibiotic resistance is a growing global health concern prompting researchers to seek alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) are emerging therapeutic agents with promising utility in this domain and using in silico methods to discover novel AMPs is a strategy that is gaining interest. Such methods can filter through large volumes of candidate sequences and reduce lab screening costs. Here we introduce AMPlify, an attentive deep learning model for AMP prediction, and demonstrate its utility in prioritizing peptide sequences derived from the Rana [Lithobates] catesbeiana (bullfrog) genome. We tested the bioactivity of our predicted peptides against a panel of bacterial species, including representatives from the World Health Organizations "priority pathogens" list. Four of our novel AMPs were active against multiple species of bacteria, including a multi-drug resistant isolate of carbapenemase-producing Escherichia coli, demonstrating the utility of tools like AMPlify in our fight against antibiotic resistance.

bioinformatics↗

bioRxiv2019

Sleep differentially affects early and late neuronal responses to sounds in auditory and perirhinal cortices

A fundamental feature of sleep is reduced behavioral responsiveness to external events, but the extent of processing along sensory pathways remains poorly understood. While responses are comparable across wakefulness and sleep in auditory cortex (AC), neuronal activity in downstream regions remains unknown. Here we recorded spiking activity in 435 neuronal clusters evoked by acoustic stimuli in the perirhinal cortex (PRC) and in AC of freely behaving male rats across wakefulness and sleep. Neuronal responses in AC showed modest (around 10%) differences in response gain across vigilance states, replicating previous studies. By contrast, PRC neuronal responses were robustly attenuated by 47% and 36% during NREM sleep and REM sleep, respectively. Beyond the separation according to cortical region, response latency in each neuronal cluster was correlated with the degree of NREM sleep attenuation, such that late (>40ms) responses in all monitored regions diminished during NREM sleep. The robust attenuation of late responses prevalent in PRC represents a novel neural correlate of sensory disconnection during sleep, opening new avenues for investigating the mediating mechanisms.\n\nSignificance StatementReduced behavioral responsiveness to sensory stimulation is at the core of sleeps definition, but it is still unclear how the sleeping brain responds differently to sensory stimuli. In the current study we recorded neuronal spiking responses to sounds along the cortical processing hierarchy of rats during wakefulness and natural sleep. Responses in auditory cortex only showed modest changes during sleep, whereas sleep robustly attenuated the responses of neurons in high-level perirhinal cortex. We also found that during NREM sleep, the response latency predicts the degree of sleep attenuation in individual neurons above and beyond their anatomical location. These results provide anatomical and temporal signatures of sensory disconnection during sleep and pave the way to understanding the underlying mechanisms.

neuroscience↗

bioRxiv2019

Locus-coeruleus norepinephrine activity gates sensory-evoked awakenings from sleep

A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms gating sensory-evoked arousal remain unclear. We hypothesized that reduced locus-coeruleus norepinephrine (LC-NE) activity during sleep mediates unresponsiveness, and its action promotes sensory-evoked awakenings. We tested this using electrophysiological, behavioral, pharmacological, and optogenetic techniques alongside auditory stimulation in freely behaving rats. We found that systemic reduction of NE signaling lowered probability of sound-evoked awakenings (SEAs). The level of tonic LC activity during sleep anticipated SEAs. Optogenetic LC activation promoted arousal as evident in sleep-wake transitions, EEG desynchronization, and pupil dilation. Importantly, liminal LC excitation before sound presentation increased SEA probability. Optogenetic LC silencing using a soma-targeted anion-conducting channelrhodopsin (stGtACR2) suppressed LC spiking and constricted pupils. Brief periods of LC opto-silencing reduced the probability of SEAs. Thus, LC-NE activity determines the likelihood of sensory-evoked awakenings and its reduction during sleep constitutes a key factor mediating behavioral unresponsiveness.

neuroscience↗