Biology subjects

Wigren, H.-K.

Publications and source records attributed to Wigren, H.-K..

3 recordsLinked to original sources

bioRxiv2026

Flavonoid chronotherapy normalizes circadian dynamics and sleep architecture in mice with painful nerve injury

Neuropathic pain (NP) is linked to disrupted sleep and circadian abnormalities upon painful peripheral nerve injury. By performing spared nerve injury (SNI) in circadian reporter PER2::LUC mice, we characterized the real-time changes in rhythmicity of the core clock gene Per2 in the pain-regulating dorsal root ganglia (DRG), and the sleep-wake cycle using wireless EEG/EMG under NP conditions. We further evaluated whether the clock-resynchronizing flavonoids, nobiletin (2 mg/kg/day) and tangeretin (1.8 mg/kg/day), administered continuously via osmotic minipumps for two weeks, could restore circadian dynamics and alleviate pain-related behaviour. Both flavonoids alleviated SNI-induced dynamic hypersensitivity in PER2::LUC mice on post-surgical day 14. SNI increased the amplitude of Per2 rhythms in the DRGs, which was restored to pre-surgical levels by administration of flavonoids. In addition, tangeretin showed sleep-restoring properties upon SNI by alleviating disturbances in NREM sleep and wakefulness. These results support targeting circadian disruption as a potential chronotherapeutic approach to alleviate NP.

neuroscience↗

bioRxiv2022

Physiological alterations in microglial morphology associate with the sleep-wake cycle in a brain region-specific manner

Long-term total sleep deprivation induces changes in cortical - and hippocampal microglial morphology that closely resemble the microglial response to the gram-negative bacterial cell wall component lipopolysaccharide (LPS). A recent study found evidence that microglia could modify vigilance-states/sleep, but only few studies investigated microglial throughout the diurnal behavioral inactivity/activity pattern or the naturally occurring sleep-wake cycle, and those who have, only concentrated on the cortical or hippocampal microglia. As microglia demonstrate regional heterogeneity, we compared microglial diurnal morphological alterations in the somatosensory cortex (SC) and dorsal hippocampus (HC) to the basal forebrain (BF), which is a subcortical brain area involved in the regulation of vigilance states. We collected mouse brain samples every 3h throughout the 24h light-dark-cycle and applied a 3D reconstruction method for the acquired confocal microscopy images for each brain area separately. While microglial regional heterogeneity was evident, stimulation of microglia with LPS caused comparable microglial responses in all brain areas. When comparing microglial features between the 12h light- and dark periods, regional heterogeneity re-appeared. As most of the morphological alterations occurred during the light period-the habitual sleeping period of the mice, we performed polysomnography to study the possible interaction of microglial morphology and sleep. We found that cortical-, but not HC- or BF microglial territory and volume negatively correlated with sleep slow wave activity (SWA), an electroencephalic feature of non-REM sleep (NREMS). Since microglia are sensitive to neuronal activity, we propose that the regional differences reflect vigilance-state specific neuronal activity patterns. Table of contents image O_FIG O_LINKSMALLFIG WIDTH=184 HEIGHT=200 SRC="FIGDIR/small/482976v1_ufig1.gif" ALT="Figure 1"> View larger version (71K): org.highwire.dtl.DTLVardef@112d346org.highwire.dtl.DTLVardef@ecc138org.highwire.dtl.DTLVardef@1817331org.highwire.dtl.DTLVardef@1b1b47c_HPS_FORMAT_FIGEXP M_FIG C_FIG Main PointsMicroglia show morphological differences between the somatosensory cortex (SC), hippocampus (HC) and basal forebrain (BF) under physiological conditions. Cortical-, but not HC- or BF microglial cell volume negatively correlates with non-REM sleep slow wave activity.

neuroscience↗

bioRxiv2018

Putative rapid-acting antidepressant nitrous oxide ("laughing gas") evokes rebound emergence of slow EEG oscillations during which TrkB signaling is induced

Electroconvulsive therapy (ECT) remains among the most efficient antidepressants but it seldom brings immediate remedy. However, a subanesthetic dose of NMDA-R (N-methyl-D-aspartate receptor) blocker ketamine ameliorates symptoms of depression already within hours. Glutamatergic excitability and regulation of TrkB neurotrophin receptor and GSK3{beta} (glycogen synthase kinase 3{beta}) signaling are considered as molecular-level determinants for ketamines antidepressant effects. Recent clinical observations suggests that nitrous oxide (N2O, \"laughing gas\"), another NMDA-R blocking dissociative anesthestic, also produces rapid antidepressant effects but the underlying mechanisms remain essentially unstudied. In this animal study we show that N2O, with a clinically relevant dosing regimen, evokes an emergence of rebound slow EEG (electroencephalogram) oscillations, a phenomenon considered to predict the efficacy and onset-of-action ECT. Very similar rebound slow oscillations are induced by subanesthetic ketamine and flurothyl (a treatment analogous to ECT). These responses become best evident upon drug withdrawal, i.e. after the peak of acute pharmacological actions, when their most prominent effects on cortical excitability have subsided. Most importantly, TrkB and GSK3{beta} signaling remain unchanged during N2O administration (ongoing NMDA-R blockade) but emerge gradually upon gas withdrawal along with increased slow EEG oscillations. Collectively these findings reveal that rapid-acting antidepressants produce cortical excitability that triggers \"a brain state\" dominated by ongoing slow oscillations, sedation and drowsiness during which TrkB and GSK3{beta} signaling alterations are induced.

pharmacology and toxicology↗