Biology subjects

Hur, K.-H.

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

6 recordsLinked to original sources

bioRxiv2026

Δ⁹-Tetrahydrocannabinol-induced enhancement of reward responsivity via mesocorticolimbic modulation in squirrel monkeys

{Delta}9-tetrahydrocannabinol (THC)-containing products are widely used recreationally, partly due to THCs ability to enhance the appetitive (i.e., rewarding) properties of diverse stimuli. However, the neural mechanisms through which THC modulates reward-related processing remain poorly understood. Here, we used a Pavlovian paradigm in adult squirrel monkeys (3males, 1female) to associate a visual conditioned stimulus (CS+) with appetitive food delivery. The modulatory effects of acute THC (1-10g/kg, i.m.) on behavioral and brain responses to CS+ were evaluated. Event-related functional MRI (fMRI) was employed to characterize the neural correlates of conditioned responding to the CS+, both in the absence and presence of THC treatment, with preconditioning scans serving as control. Behaviorally, THC (3g/kg) selectively enhanced conditioned responding to the CS+ without altering responses to the control stimulus (CS-) or increasing baseline consummatory responding, underscoring the specificity of THCs action on reward-associated processes. Consistently, fMRI analyses revealed that THC amplified CS+-evoked activation within mesocorticolimbic regions, including the anterior cingulate cortex (ACC), striatum, hippocampus, and substantia nigra-ventral tegmental area (SN-VTA), without affecting activity in visual and motor cortices. This finding underscores the selectivity of THCs neuromodulatory effects on reward-related circuitry. Independent of CS exposure, resting-state functional connectivity analyses indicate that THC enhanced mesocorticolimbic network integration, as evident in strengthened SN-VTA-centered connectivity with the ACC, striatum, and hippocampus. Collectively, these findings demonstrate that THC enhances the responses to appetitive stimuli, through selective modulation of mesocorticolimbic circuitry, highlighting the SN-VTA as a pivotal hub for cannabinoid-mediated regulation of incentive salience and motivational drive toward reward-associated stimuli. One-sentence summariesTHC enhances behavioral and neural responses to rewards through mesocorticolimbic modulation centered on the SN-VTA.

neuroscience↗

bioRxiv2025

Nociceptin/Orphanin FQ receptor agonism attenuates behavioral and neural responses to conditioned aversive stimuli

The nociceptin/orphanin FQ peptide (NOP) receptor has emerged as a promising anxiolytic target, as its activation has been shown to reduce anxiety-related behaviors in rodents. However, the mechanisms underlying these effects are not well understood. Here, we investigated the effects of the selective NOP receptor agonist SCH-221510 (SCH; 0.01-0.1 mg/kg, IM) on behavioral and neural responses to aversive stimuli in squirrel monkeys (n=3). Subjects underwent Pavlovian fear conditioning, wherein a visual conditioned stimulus (CS) was paired with the presentation of an aversive stimulus. Event-related fMRI was conducted in awake subjects to evaluate CS-evoked neural responses. Behavioral and neural responses to the CS were assessed across three experimental phases: pre-conditioning (Pre-C), post-conditioning (Post-C), and Post-C with SCH administration. In behavioral assessments, CS presentation during Post-C elicited a robust suppression of ongoing operant responding, which was absent during Pre-C and significantly attenuated by SCH treatment (0.1 mg/kg). Functional magnetic resonance imaging (fMRI) results revealed that, relative to Pre-C, CS presentation during Post-C was associated with increased BOLD activity in brain regions previously implicated in fear processing (e.g., amygdala), expression and regulation (e.g., prefrontal cortex; PFC), as well as sensory integration. Critically, SCH (0.1 mg/kg) administration significantly attenuated CS-induced neural activation in these regions. Furthermore, resting-state functional connectivity analysis revealed that SCH administration decreased connectivity between the PFC and the amygdala, while enhancing connectivity among subregions of the PFC. Collectively, these findings suggest that NOP receptor agonism may attenuate conditioned responses to aversive stimuli by modulating functional interactions within the PFC-amygdala circuit.

neuroscience↗

bioRxiv2025

Enhanced anti-nociception by novel dual antagonists for 5HT2aR and mGluR5 in preclinical models of pain

Significant research has focused on developing anti-nociceptive pain treatments by targeting specific molecular candidates. The serotonin 2A receptor (5-HT2AR) and metabotropic glutamate receptor 5 (mGluR5) are recognized as key mediators in neuropathic pain. However, the combined effects of simultaneous inhibition of these targets remain unexplored. This current study investigated the therapeutic potential of concurrently antagonizing 5-HT2AR and mGluR5. Using spinal nerve ligation (SNL) and formalin-induced pain models in male Sprague-Dawley rats, we demonstrated that the simultaneous administration of both antagonists significantly enhanced anti-allodynic and anti-nociceptive effects, resulting in increased allodynia thresholds and reduced pain-related behaviors. This dual antagonism provided pain relief comparable to that of gabapentin and morphine. Furthermore, novel small molecules designed to simultaneously antagonize 5-HT2AR and mGluR5 exerted anti-nociceptive effects by suppressing excitatory postsynaptic responses and inhibiting the phosphorylation of ERK and AKT signaling molecules. Notably, the dual antagonist maintained anti-allodynic efficacy with repeated administration, unlike morphine, which exhibited clear tolerance development with daily use. Moreover, when administered intravenously, the dual antagonist demonstrated a low potential for abuse. These findings indicate that the simultaneous antagonism of 5-HT2AR and mGluR5 represents a promising pharmacological target for the management of chronic pain. This approach may offer enhanced analgesic outcomes while reducing the risk of undesirable side effects, such as tolerance and the potential for abuse.

neuroscience↗

bioRxiv2021

The luminal AAA+ ATPase torsinA mediates distinct mechanisms of nuclear-cytoplasmic communication by adopting different functional assembly states.

Chemical and mechanical nuclear-cytoplasmic communication across the nuclear envelope (NE) is largely mediated by the nuclear pore complex (NPC) and the linker of nucleoskeleton and cytoskeleton (LINC) complex, respectively. While NPC and LINC complex assembly are functionally related, the mechanisms responsible for this relationship remain poorly understood. Here, we investigated how the luminal ATPases associated with various cellular activities (AAA+) protein torsinA promotes NPC and LINC complex assembly using fluorescence fluctuation spectroscopy (FFS), quantitative photobleaching analyses, and functional cellular assays. We report that torsinA controls LINC complex-dependent nuclear-cytoskeletal coupling as a soluble hexameric AAA+ protein and interphase NPC biogenesis as a membrane-associated helical polymer. These findings help resolve the conflicting models of torsinA function that were recently proposed based on in vitro structural studies. Our results will enable future studies of the role of defective nuclear-cytoplasmic communication in DYT1 dystonia and other diseases caused by mutations in torsinA.

cell biology↗

bioRxiv2020

Comparative Evaluation of cobas Influenza A/B & RSV and Simplexa Flu A/B & RSV for Rapid Detection of Influenza and Respiratory Syncytial Viruses

We compared two molecular point-of-care tests, the cobas Influenza A/B & RSV (cobas Liat) and the Simplexa Flu A/B & RSV (Simplexa). A total of 236 respiratory specimens from patients referred for respiratory viruses testing were retrospectively evaluated; 53 specimens tested positive for each of Flu A, Flu B, and RSV, and 77 specimens tested negative based on the results of the reference method, i.e. the Seegene Allplex Respiratory Panel 1/2/3 (Seegene, Seoul, Korea). The turnaround time (TAT) was 20 min per specimen for cobas Liat and 78 min per eight specimens for Simplexa. The numbers of invalid results were one (0.4%) in cobas Liat and 10 (4.2%) in Simplexa (p < 0.05). All results were consistent with those of the reference method in cobas Liat. The sensitivity and specificity for Flu A, Flu B and RSV A were 100% with Simplexa. However, the sensitivity for RSV B was 80.0% with Simplexa, which was significantly lower than that of cobas Liat (p < 0.05). Comparison of the cycle threshold (Ct) values for RSV with Simplexa and the reference method showed the correlation as continuous variables (p < 0.001) with a higher propensity for obtaining Ct values with Simplexa, the exception being the six false negative results; their Ct values were more than 30 in the reference method. Cobas Liat showed high sensitivity for the detection of RSV B with rapid TAT, and a good workflow efficiency.

microbiology↗

bioRxiv2019

Identifying hetero-protein complexes in the nuclear envelope

The nucleus is delineated by the nuclear envelope (NE), which is a double membrane barrier composed of the inner and outer nuclear membranes as well as a ~40 nm wide lumen. In addition to its barrier function, the NE acts as a critical signaling node for a variety of cellular processes which are mediated by protein complexes within this subcellular compartment. While fluorescence fluctuation spectroscopy (FFS) is a powerful tool for characterizing protein complexes in living cells, it was recently demonstrated that conventional FFS methods are not suitable for applications in the NE because of the presence of slow nuclear membrane undulations. We previously addressed this challenge by developing time-shifted mean-segmented Q (tsMSQ) analysis and applied it to successfully characterize protein homo-oligomerization in the NE. However, many NE complexes, such as the linker of the nucleoskeleton and cytoskeleton (LINC) complex, are formed by heterotypic interactions, which single-color tsMSQ is unable to characterize. Here, we describe the development of dual-color (DC) tsMSQ to analyze NE hetero-protein complexes built from proteins that carry two spectrally distinct fluorescent labels. Experiments performed on model systems demonstrate that DC tsMSQ properly identifies hetero-protein complexes and their stoichiometry in the NE by accounting for spectral crosstalk and local volume fluctuations. Finally, we applied DC tsMSQ to study the assembly of the LINC complex, a hetero-protein complex composed of Klarsicht/ANC-1/SYNE homology (KASH) and Sad1/UNC-84 (SUN) proteins, in the NE of living cells. Using DC tsMSQ, we demonstrate the ability of the SUN protein SUN2 and the KASH protein nesprin-2 to form a hetero-complex in vivo. Our results are consistent with previously published in vitro studies and demonstrate the utility of the DC tsMSQ technique for characterizing NE hetero-protein complexes.\n\nStatement of SignificanceProtein complexes found within the nuclear envelope (NE) play a vital role in regulating cellular functions ranging from gene expression to cellular movement. However, the assembly state of these complexes within their native environment remains poorly understood, which is compounded by a general lack of fluorescence techniques suitable for quantifying the oligomeric state of NE protein complexes. This study aims at addressing this issue by introducing dual-color time-shifted mean-segmented Q analysis as a fluorescence fluctuation method specifically designed to identify the average oligomeric state of hetero-protein complexes within the NE of living cells.

biophysics↗