Biology subjects

Lee, K. H.

Publications and source records attributed to Lee, K. H..

At least 19 recordsLinked to original sources

bioRxiv2026

Human and Mouse Models of the Bipolar Disorder-Associated ANK3 p.W1989R Variant Display Altered Somatostatin Interneuron Connectivity and Function

Bipolar disorder (BD) is a debilitating neuropsychiatric disorder characterized by recurrent mood perturbations, cognitive and functional impairment, and increased risk of suicide. Genome-wide association studies (GWAS) have repeatedly identified the gene ANK3, which encodes the neuronal scaffolding protein ankyrin-G, as a risk locus for BD. Ankyrin-G interacts directly with the GABAA receptor-associated protein (GABARAP) to stabilize inhibitory synapses, providing a potential mechanistic link between ANK3 variation and GABAergic dysfunction observed in BD. Previously, we identified an ANK3 p.W1989R variant in a family with BD and demonstrated that this variant abolishes the ankyrin-G/GABARAP interaction, resulting in inhibitory signaling deficits in mice. Here, we investigated the effects of this variant in human induced pluripotent stem cell (hiPSC)-derived neurons generated from an affected individual heterozygous for the ANK3 p.W1989R variant. CRISPR correction of the variant increased inhibitory synapse density on both glutamatergic and GABAergic patient-derived neurons. Integrated spatial transcriptomics and calcium imaging identified cell-type-dependent changes in gene expression and calcium dynamics. ANK3 p.W1989R somatostatin (SST) positive interneurons displayed altered calcium dynamics and reduced SST expression. To determine whether the variant impacts SST interneuron-mediated inhibition of cortical circuits, we selectively stimulated prefrontal cortical SST interneurons in heterozygous Ank3 p.W1989R mice and recorded optically evoked inhibitory postsynaptic currents (oIPSCs) from cortical pyramidal neurons. SST interneuron-mediated oIPSC peak amplitude, charge transfer, and decay times were reduced in variant mice, without a significant change in the paired-pulse ratio. These findings, using complementary human and mouse models, identify novel roles for ankyrin-G in SST interneuron-mediated inhibitory signaling and demonstrate that altered inhibitory connectivity and SST interneuron function are associated with ANK3 p.W1989R. This work provides mechanistic insight into how disrupted ankyrin-G-dependent synaptic function may contribute to inhibitory signaling deficits relevant to BD.

neuroscience↗

bioRxiv2026

A cognitive representation in primary visual cortex modulated by vision

Primary visual cortex (V1) is a critical substrate for mammalian vision. Traditionally, visual inputs are thought to be the main drivers of V1 activity, with internal signals playing a modulatory role. Here we show that this relationship is inverted for a large fraction of V1 neurons. In rats completing a navigation task in darkness, these neurons encoded progress along physically distinct paths with a shared turn structure. Under illumination, visual stimuli gain-modulated this path-invariant activity rather than replacing it with stimulus-driven responses. Path-invariant V1 neurons were also preferentially coordinated with hippocampal ensembles during sharp-wave ripples, linking them to a brain-wide network involved in learning. These findings establish that an internal model of the world can serve as a primary driver of activity in sensory cortex.

neuroscience↗

bioRxiv2026

Programmed Clonal Expansion Drives an ATM-Dependent Vulnerability Underlying Preferential Lymphocyte Depletion and Myeloid Bias Following DNA Damage

Myeloid bias is a hallmark of aging and genotoxic stress, yet the mechanisms underlying the preferential suppression of lymphopoiesis and the resulting predominance of myeloid cells following DNA damage remain incompletely understood. Here, we systematically characterized the acute hematopoietic response to a clinically relevant 2 Gy dose of ionizing radiation in young adult mice. Forty-eight hours after irradiation, overall bone marrow cellularity was reduced by [~]50-60%, with hematopoietic stem and progenitor cells (HSPCs) and myeloid populations declining proportionally. Strikingly, immature and naive B cells in the bone marrow and developing T cells in the thymus exhibited profound hypersensitivity, declining by [~]90%, thereby recapitulating the preferential vulnerability of lymphocytes to DNA damage. Single-cell RNA sequencing mapped this vulnerability to cells undergoing programmed clonal expansion associated with V(D)J recombination. Specifically, B and T lymphocytes immediately following productive V(D)J recombination at the immunoglobulin heavy-chain (IgH) and T-cell receptor {beta} (TCR{beta}) loci were the most radiosensitive, resulting in the marked depletion of the immediately downstream small pre-B and CD4CD8 double-positive (DP) thymocyte populations. Mechanistically, this stage-specific radiosensitivity was mediated by ATM-dependent DNA damage responses, as Atm deficiency selectively rescued the hypersensitivity of clonally expanding lymphoid progenitors while leaving the global reduction of HSPCs and myeloid cells largely unchanged. Rapidly proliferating S3 erythroblasts also exhibited a similar ATM-dependent hypersensitivity, suggesting that programmed proliferative bursts may represent a general determinant of radiation sensitivity. Together, these findings identify programmed clonal expansion associated with V(D)J recombination as an intrinsic developmental vulnerability that underlies the preferential suppression of lymphopoiesis following DNA damage and provides a mechanistic explanation for the emergence of myeloid bias. Key PointsO_LI2 Gy irradiation preferentially depletes developing mouse B and T cells beyond global hematopoietic loss C_LIO_LIProgrammed clonal expansion drives ATM-dependent DNA damage sensitivity in developing lymphocytes. C_LI

genetics↗

bioRxiv2025

VISTA-FISH: Video Imaging with Spatial-Temporal Analysis by Fluorescent In Situ Hybridization

Performing live-cell microscopy and high-dimensional gene expression measurements on the same cells is crucial for unraveling the molecular mechanisms underlying complex temporal phenotypes, yet this remains challenging using traditional approaches. To address these limitations, we developed Video Imaging with Spatial-Temporal Analysis by FISH (VISTA-FISH), a technique that matches live-cell recordings of cultured cells with the expression of thousands of genes in the same cell at the end of the video. Moreover, VISTA-FISH can simultaneously detect CRISPR guide RNAs in pooled screens, enabling investigation into the fundamental underpinnings of cellular activity, organelle transport, and other pivotal cellular functions. Using VISTA-FISH, we measured gene expression and neuron activity in the same differentiating neurons. This combined single-cell transcriptomic and video data allowed us to link differentiation stage, subcellular transcript localization, and cell subtype with neuron activity. Using these measurements, we built a model to predict activity from expression. Finally, we performed a pooled CRISPR interference screen with live-cell lysosome imaging, identifying alterations in lysosome movement and morphology as well as gene expression in perturbed neurons. Collectively, these studies position VISTA-FISH as a powerful new tool for elucidating the molecular mechanisms underlying neuron activity, organelle trafficking, and other complex temporal phenotypes.

molecular biology↗

bioRxiv2025

ΔCt-Informed, Calibrated Logistic Regression Accurately Attributes mecA in Staphylococcus aureus-Positive Wound Specimens.

In wound specimens, co-detection of mecA and Staphylococcus aureus by PCR does not necessarily indicate MRSA because coagulase-negative staphylococci (CoNS) frequently harbor mecA. We evaluated a {Delta}Ct-informed, biologically gated, calibrated logistic regression to attribute mecA to S. aureus versus CoNS. Using paired culture/AST and multiplex real-time PCR Ct values (internal n=93; external n=47), we trained 5-fold cross-validated models in the culture-positive S. aureus subset (n=36) and applied an S. aureus PCR gate (no attribution when S. aureus PCR is negative). The primary model achieved sensitivity 90.9% and specificity 92.0% for MRSA attribution with AUC 0.931 (out-of-fold). Decision curve analysis showed positive net benefit across clinically relevant thresholds; at the prespecified 50% cutoff, the model achieved a net benefit of 0.222 compared with negative benefit for a treat-all strategy. In an external cohort, S. aureus detection by PCR versus culture showed 92.3% sensitivity and 97.1% specificity; within S. aureus PCR-positives (n=12), MRSA attribution reached 100% sensitivity and 87.5% specificity (accuracy = 91.7%). This framework improves mecA interpretability in polymicrobial specimens and can reduce unnecessary MRSA-directed antibiotics.

microbiology↗

bioRxiv2025

Garcinone C suppressed the proliferation of gastric cancer cells through regulating Hedgehog signaling

Garcinone C, a xanthone derived from Garcinia mangostana L, possesses antioxidant and anti-cancer effects. However, its role in gastric cancer remains unexplored. This study aimed to investigate the effects of garcinone C on gastric cancer cell proliferation and its underlying mechanism. We found that garcinone C suppressed gastric cancer cell growth by inducing G0/G1 arrest and apoptosis in a dose-dependent manner. Furthermore, garcinone C downregulated G0/G1 phase markers Cyclin D1 and p21, as well as apoptosis markers Bax, Bcl-2, cleaved-PARP, and c-caspase 3. Following the previous evidence demonstrated that aberrant Hedgehog (Hh) signaling is implicated in gastric cancer development, we confirmed that inhibiting Gli1/2 reduced the growth of AGS and MKN74 cells. Furthermore, garcinone C exerted similar effects to Gant61, inhibiting Hh signaling by reducing Gli1/2 levels and blocking their nuclear translocation. These findings suggest that garcinone C inhibits gastric cancer proliferation via the Hh signaling, indicating its potential as a therapeutic agent for treating gastric cancer.

cancer biology↗

bioRxiv2024

Flux balance analysis and peptide mapping elucidate the impact of bioreactor pH on Chinese Hamster Ovary (CHO) cell metabolism and N-linked glycosylation in the Fab and Fc regions of the produced IgG

Chinese Hamster Ovary (CHO) cells were grown at different bioreactor pH conditions to detail how bioreactor pH affects cell metabolism and site-specific N-linked glycosylation of the produced broadly neutralizing anti-HIV IgG monoclonal antibody VRC01. The data show that pH affects cell growth, glucose/lactate metabolism, IgG production rates, nonessential amino acid metabolism and ammonia accumulation. Parsimonious Flux Balance Analysis (pFBA) and Flux Variability Analysis (FVA) provide insight into the effect of pH on core intracellular reactions at the different pH conditions and culture durations. pFBA revealed the contribution of sources for the production of the toxic metabolite ammonia and provided insights into the switch from ammonia production to consumption. It also documented that culture duration and pH alter the complex bimodal patterns (production/uptake) of several essential and non-essential amino acids. The VRC01 IgG has N-linked glycosylation sites in both the Fc region and the Fab region. Site- specific N-linked glycan analysis using glycopeptide mapping demonstrated that pH significantly affects the glycosylation profiles of the two IgG sites. The Fc region glycans were completely fucosylated but did not contain any sialylation. The Fab region glycans were not completely fucosylated but contained sialylated glycans. Bioreactor pH affected both the fucosylation and sialylation indexes in the Fab region and the galactosylation index of the Fc region. However, fucosylation in the Fc region was unaffected thus demonstrating that the effect of pH on site- specific N-linked glycosylation is complex.

bioengineering↗

bioRxiv2024

plantMASST - Community-driven chemotaxonomic digitization of plants

Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.

plant biology↗

bioRxiv2024

A subtle modification of modafinil-based DAT inhibitors changes conformational preference

Modafinil analogs with either a sulfoxide or sulfide moiety have improved binding affinities at the human dopamine transporter (hDAT) compared to modafinil, with lead sulfoxide-substituted analogs showing characteristics of atypical inhibition (e.g., JJC8-091). Interestingly, the only distinction between sulfoxide and sulfide substitution is the presence of one additional oxygen atom. To elucidate why such a subtle difference in ligand structure can result in different typical or atypical profiles, we investigated two pairs of analogs. Our quantum mechanical calculations revealed a more negatively charged distribution of electrostatic potential surface of the sulfoxide substitution. Using molecular dynamics simulations, we demonstrated that sulfoxide-substituted modafinil analogs have a propensity to attract more water into the binding pocket. They also exhibited a tendency to dissociate from Asp79 and form a new interaction with Asp421, consequently promoting an inward-facing conformation of DAT. In contrast, sulfide-substituted analogs did not display these effects. These findings deepen our understanding of the functionally relevant conformational spectrum of DAT.

biophysics↗

bioRxiv2024

Unlocking the Potential of High-Quality Dopamine Transporter Pharmacological Data: Advancing Robust Machine Learning-Based QSAR Modeling

The dopamine transporter (DAT) plays a critical role in the central nervous system and has been implicated in numerous psychiatric disorders. The ligand-based approaches are instrumental to decipher the structure-activity relationship (SAR) of DAT ligands, especially the quantitative SAR (QSAR) modeling. By gathering and analyzing data from literature and databases, we systematically assemble a diverse range of ligands binding to DAT, aiming to discern the general features of DAT ligands and uncover the chemical space for potential novel DAT ligand scaffolds. The aggregation of DAT pharmacological activity data, particularly from databases like ChEMBL, provides a foundation for constructing robust QSAR models. The compilation and meticulous filtering of these data, establishing high-quality training datasets with specific divisions of pharmacological assays and data types, along with the application of QSAR modeling, prove to be a promising strategy for navigating the pertinent chemical space. Through a systematic comparison of DAT QSAR models using training datasets from various ChEMBL releases, we underscore the positive impact of enhanced data set quality and increased data set size on the predictive power of DAT QSAR models.

bioinformatics↗

bioRxiv2024

Regional specialization manifests in the reliability of neural population codes

The brain has the remarkable ability to learn and guide the performance of complex tasks. Decades of lesion studies suggest that different brain regions perform specialized functions in support of complex behaviors1-3. Yet recent large-scale studies of neural activity reveal similar patterns of activity and encoding distributed widely throughout the brain4-6. How these distributed patterns of activity and encoding are compatible with regional specialization of brain function remains unclear. Two frontal brain regions, the dorsal medial prefrontal cortex (dmPFC) and orbitofrontal cortex (OFC), are a paradigm of this conundrum. In the setting complex behaviors, the dmPFC is necessary for choosing optimal actions2,7,8, whereas the OFC is necessary for waiting for3,9 and learning from2,7,9-12 the outcomes of those actions. Yet both dmPFC and OFC encode both choice- and outcome-related quantities13-20. Here we show that while ensembles of neurons in the dmPFC and OFC of rats encode similar elements of a cognitive task with similar patterns of activity, the two regions differ in when that coding is consistent across trials ("reliable"). In line with the known critical functions of each region, dmPFC activity is more reliable when animals are making choices and less reliable preceding outcomes, whereas OFC activity shows the opposite pattern. Our findings identify the dynamic reliability of neural population codes as a mechanism whereby different brain regions may support distinct cognitive functions despite exhibiting similar patterns of activity and encoding similar quantities.

neuroscience↗

bioRxiv2024

Spyglass: a data analysis framework for reproducible and shareable neuroscience research

Scientific progress depends on reliable and reproducible results. Progress can be accelerated when data are shared and re-analyzed to address new questions. Current approaches to storing and analyzing neural data involve bespoke formats and software that make replication and reuse of data difficult. To address these challenges, we created Spyglass, an open-source data management and analysis framework written in Python. Spyglass provides reproducible pipelines for common neuroscience analyses and sharing of raw data, intermediate analyses, and final results within and across labs. Spyglass uses the Neurodata Without Borders (NWB) standard and includes pipelines for spectral filtering, spike sorting, pose tracking, and neural decoding. Spyglass can be extended to apply existing and newly developed pipelines to datasets from multiple sources. We demonstrate these features in the context of a cross-laboratory replication by applying advanced state space decoding algorithms to publicly available data. New users can try out Spyglass on a Jupyter Hub hosted by HHMI and 2i2c: https://spyglass.hhmi.2i2c.cloud/.

neuroscience↗

bioRxiv2024

The unseen invaders: tracking phylogeographic dynamics and genetic diversity of cryptic Pomacea canaliculata and P. maculata (Golden Apple Snails) across Taiwan

The cryptic invasion of golden apple snails (Pomacea canaliculata and P. maculata) in Taiwan has caused significant ecological and economical damage over last few decades, however, their management remains difficult due to inadequate taxonomic identification, complex phylogeny and limited population genetic information. We aim to understand the current distribution, putative population of origin, genetic diversity and potential path of cryptic invasion of Pomacea canaliculata and P. maculata across Taiwan to aid in improved mitigation approaches. The present investigation conducted a nationwide survey with 254 samples collected from 41 locations from 14 counties or cities across Taiwan. We identified P. canaliculata and P. maculata based on mitochondrial COI and compared their genetic diversity across Taiwan, as well as other introduced and native countries (based on publicly available COI data) to understand the possible paths of invasion in Taiwan. Based on mitochondrial COI barcoding, sympatric and heterogeneous distributions of invasive P. canaliculata and P. maculata were noted. Our haplotype analysis and mismatch distribution suggested multiple introductions of P. canaliculata in Taiwan was likely originated directly from Argentina, whereas P. maculata was probably introduced from a single, or a few, introduction event(s) from Argentina and Brazil. Our population genetic data further demonstrated a higher haplotype and genetic diversity for P. canaliculata and P. maculata in Taiwan compared to other introduced regions. Based on our current understanding, the establishment of P. canaliculata and P. maculata is alarming and widespread beyond geopolitical borders, requiring a concerted and expedited national and international invasive species mitigation program.

ecology↗

bioRxiv2024

Linkers in bitopic agonists shape bias profile among transducers for the dopamine D2 and D3 receptors

Bitopic ligands bind both orthosteric and allosteric or secondary binding sites within the same receptor, often resulting in improvement of receptor selectivity, potency, and efficacy. In particular, for both agonists and antagonists of the dopamine D2 and D3 receptors (D2R and D3R), the primary therapeutic targets for several neurological and neuropsychiatric disorders, bitopic ligand design has proved advantageous in achieving better pharmacological profiles in vitro. Although the two pharmacophores within a bitopic ligand are typically considered the main drivers of conformational change for a receptor, the role of the linker that connects the two has not yet been systematically studied for its relevance in receptor activity profiles. Here, we present a comprehensive analysis of sumanirole and PF592,379-based indole-containing bitopic compounds in agonist activity at D2R and D3R, with a focus on linker chemical space and stereochemistry achieved through testing seven distinct chirally resolved linkers. The current study examines the structure activity relationships (SAR) of these linkers extensively, beyond the conventional level, by characterizing activation of all putative transducers over a 44 min time course. Our multiparametric analysis provides previously unappreciated clarity of linker-dependent effects, highlighting the utility of this applied comprehensive approach and the significance of linker type in the shaping of transducer bias profiles.

pharmacology and toxicology↗

bioRxiv2023

Unraveling activation-related rearrangements and intrinsic divergence from ligand-induced conformational changes of the dopamine D3 and D2 receptors

Effective rational drug discovery targeting a specific protein hinges on understanding their functional states and distinguishing it from homologs. However, for the G protein coupled receptors, both the activation-related conformational changes (ACCs) and the intrinsic divergence among receptors can be misled or obscured by ligand-induced conformational changes (LCCs). Here, we unraveled ACCs and intrinsic divergence from LCCs of the dopamine D3 and D2 receptors (D3R and D2R), by analyzing their experimentally determined structures and the molecular dynamics simulation results of the receptors bound with different ligands. In addition to the ACCs common to other aminergic receptors, we revealed unique ACCs for these two receptors including TM5e and TM6e shifting away from TM2e and TM3e, with a subtle rotation of TM5e. In identifying intrinsic divergence, we found pronounced outward tilting of TM6e in the D2R compared to the D3R in both experimental structures and simulations with ligands in different scaffolds. This tilting was drastically reduced in the simulations of the receptors bound with nonselective full agonist quinpirole, suggesting a misleading impact of LCCs. Further, in the quinpirole-bound simulations, TM1 showed a greater disparity between these receptors, indicating that LCCs may obscure intrinsic divergence. In addition, our analysis showed that the impact of the nonconserved TM1 propagated to conserved Trp7.40 and Glu2.65, both are ligand binding residues. We also found that the D2R exhibited heightened flexibility compared to the D3R in the extracellular portions of TMs 5, 6, and 7, potentially associated with its greater ligand binding site plasticity. Our results lay the groundwork for crafting ligands specifically targeting D2R or D3R with more precise pharmacological profiles.

biophysics↗

bioRxiv2023

Anti-manic effect of deep brain stimulation of the ventral tegmental area in an animal model of mania induced by methamphetamine

BackgroundTreatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD. AimThe present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m-amph). MethodsWistar rats were given 14 days of mamph injections, in the last day animals were submitted to 20 minutes of VTA DBS in two different patterns: intermittent low frequency stimulation (LFS) or continuous high frequency stimulation (HFS). Immediately after DBS, manic-like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open-field test and fast-scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry. ResultsM-amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. Mamph increased DA reuptake time post-sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc. ConclusionThese results demonstrate that both VTA LFS and HFS DBS exert anti-manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti-manic effects.

neuroscience↗

bioRxiv2023

Micromagnetic Stimulation (μMS) Controls Dopamine Release: An in vivo Study Using WINCS Harmoni

ObjectiveResearch into the role of neurotransmitters in regulating normal and pathologic brain functions has made significant progress. Yet, clinical trials that aim to improve therapeutic interventions do not take advantage of the in vivo changes in the neurochemistry that occur in real time during disease progression, drug interactions or response to pharmacological, cognitive, behavioral, and neuromodulation therapies. In this work, we used the WINCS Harmoni tool to study the real time in vivo changes in dopamine release in rodent brains for the micromagnetic neuromodulation therapy. ApproachAlthough still in its infancy, micromagnetic stimulation (MS) using micro-meter sized coils or microcoils (coils) has shown incredible promise in spatially selective, galvanic contact free and highly focal neuromodulation. These coils are powered by a time-varying current which generates a magnetic field. As per Faradays Laws of Electromagnetic Induction, this magnetic field induces an electric field in a conducting medium (here, the brain tissues). We used a solenoidal-shaped coil to stimulate the medial forebrain bundle (MFB) of the rodent brain in vivo. The evoked in vivo dopamine releases in the striatum were tracked in real time by carbon fiber microelectrodes (CFM) using fast scan cyclic voltammetry (FSCV). ResultsOur experiments report that coils can successfully activate the MFB in rodent brains, triggering dopamine release in vivo. We further show that the successful release of dopamine upon micromagnetic stimulation is dependent on the orientation of the coil. Furthermore, varied intensities of MS can control the concentration of dopamine releases in the striatum. SignificanceThis work helps us better understand the brain and its conditions arising from a new therapeutic intervention, like MS, at the level of neurotransmitter release. Despite its early stage, this study potentially paves the path for MS to enter the clinical world as a precisely controlled and optimized neuromodulation therapy.

neuroscience↗

bioRxiv2023

Photobiomodulation Therapy for a Novel Olfactory Dysfunction Ischemic Stroke Model

A.BackgroundIschemic stroke typically accompanies numerous disorders ranging from somatosensory dysfunction to cognitive impairments, inflicting its patients with various neurologic symptoms. Among pathologic outcomes, post-stroke olfactory dysfunction is frequently observed. Despite the well-known prevalence, therapy options for such compromised olfaction are limited, likely due to the complexity of the olfactory bulb architecture, which encompasses both the peripheral and central nervous systems. As photobiomodulation (PBM) emerged for treating stroke-associated symptoms, the effectiveness of PBM on the stroke-induced impairment of the olfactory function was explored. PurposeTo address the efficacy of PBM therapy on the olfactory bulb damage caused by ischemic stroke using both behavioral and histologic and inflammatory markers in the newly developed stroke mouse models. MethodsNovel mouse models with olfactory dysfunction were prepared using photothrombosis (PT) in the olfactory bulb on day 0. Moreover, post-PT PBM was performed daily from day 2 to day 7 by irradiating the olfactory bulb using an 808 nm laser with the fluence of 40 J/cm2 (325 mW/cm2 for 2 minutes per day). The buried food test (BFT) was used for scoring behavioral acuity in the food-deprived mice to assess the olfactory function before PT, after PT, and after PBM. Histopathological examinations and cytokine assays were performed on the mouse brains harvested on day 8. ResultsThe results from BFT were specific to the individual, with positive correlations between the baseline latency time measured before PT and alterations at the ensuing stages for both the PT and PT+PBM groups. Also in both groups, the correlation analysis showed a significant positive relationship between the early and late latency time changes independent of PBM, implicating a common recovery mechanism. In particular, the PBM treatment largely accelerated the recovery of impaired olfaction after PT with the suppression of inflammatory cytokines while enhancing both the glial and vascular factors (e.g., GFAP, IBA-1, and CD31). ConclusionsThe PBM therapy during the acute phase of ischemia improves the compromised olfactory function by modulating the microenvuronment and tissue inflammation.

neuroscience↗