Biology subjects

Kim, S. Y.

Publications and source records attributed to Kim, S. Y..

At least 55 records · Page 3Linked to original sources

bioRxiv2022

Germline Transmission of a Circular Human Artificial Chromosome in the Mouse

Although the structure and function of the alphoid-tetO Human Artificial Chromosome (tetO-HAC) has been previously described in cell culture models and somatically in the mouse, in vivo persistence and stability throughout meiosis and across generations were not evaluated. Here we report germline transmission of a circular tetO-HAC across three mouse generations without observable health or reproductive deficiencies. Furthermore, we show that the tetO-HAC is maintained without selection as an episome and can be efficiently transmitted by both ova and sperm.

synthetic biology↗

bioRxiv2022

Pleural macrophages promote recovery from influenza virus infection

Seasonal influenza results in 3 to 5 million cases of severe disease and 250,000 to 500,000 deaths annually. Macrophages have been implicated in both the resolution and progression of the disease, but the drivers of these outcomes are poorly understood. We probed mouse lung transcriptomic datasets using the Digital Cell Quantifier algorithm to predict immune cell subsets that correlated with mild or severe influenza A virus (IAV) infection outcomes. We identified a novel lung macrophage population that transcriptionally resembled small serosal cavity macrophages and correlated with mild disease. Until now, the study of serosal macrophage translocation in the context of infections has been neglected. Here, we show that pleural macrophages (PMs) migrate from the pleural cavity to the lung after infection with pH1N1 A/California/04/2009 IAV. We found that the depletion of PMs increased morbidity and pulmonary inflammation. There were increased proinflammatory cytokines in the pleural cavity and an influx of neutrophils within the lung. Our results show PMs are recruited to the lung during IAV infection and contribute to recovery from influenza. This study expands our knowledge of PM plasticity and provides a new source of lung macrophages independent of monocyte recruitment and local proliferation. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/493482v2_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1e8880borg.highwire.dtl.DTLVardef@13b987dorg.highwire.dtl.DTLVardef@19856f9org.highwire.dtl.DTLVardef@76277d_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2022

Non-Covalently Associated Streptavidin Multi-Arm Nanohubs Exhibit Mechanical and Thermal Stability in Protein-Network Materials

Constructing protein-network materials that exhibit physicochemical and mechanical properties of individual protein constituents requires molecular cross-linkers with specificity and stability. A well-known example involves specific chemical fusion of a four-arm polyethylene glycol (tetra-PEG) to desired proteins with secondary cross-linkers. However, it is necessary to investigate tetra-PEG like biomolecular cross-linkers that are genetically fused to the proteins, simplifying synthesis by removing additional conjugation and purification steps. Non-covalently, self-associating, streptavidin homotetramer is a viable, biomolecular alternative to tetra-PEG. Here, a multi-arm streptavidin design is characterized as a protein-network material platform using various secondary, biomolecular cross-linkers, such as high-affinity physical (i.e., non-covalent), transient physical, spontaneous chemical (i.e., covalent), or stimuli-induced chemical cross-linkers. Stimuli-induced, chemical cross-linkers fused to multi-arm streptavidin nanohubs provide sufficient diffusion prior to initiating permanent covalent bonds, allowing proper characterization of streptavidin nanohubs. Surprisingly, non-covalently associated streptavidin nanohubs exhibit extreme stability which translates into material properties that resemble hydrogels formed by chemical bonds even at high temperatures. Therefore, this study not only establishes that the streptavidin nanohub is an ideal multi-arm biopolymer precursor but also provides valuable guidance for designing self-assembling nanostructured molecular networks that can properly harness the extraordinary properties of protein-based building blocks.

bioengineering↗

bioRxiv2022

Single cell transcriptional landscape of long non-coding RNAs orchestrating mouse heart development

Long non-coding RNAs (lncRNAs) comprise the most representative transcriptional units of the mammalian genome, and theyre associated with organ development that can be associated with the emergence of diseases, such as cardiovascular diseases. Thus, we used bioinformatic approaches, machine learning algorithms and statistical techniques to define lncRNAs involved in mammalian cardiac development. We used a single-cell transcriptome dataset generated from 4 embryonic and 4 postnatal stages. Our study identified 8 distinct cell types, novel marker transcripts (coding/lncRNAs) and also, differential expression and functional enrichment analysis reveal cardiomyocyte subpopulations associated with cardiac function; meanwhile modular co-expression analysis reveals cell-specific functional insights for lncRNAs during myocardial development, including a potential association with key genes related to disease and the "fetal gene program". Our results evidence the role of particular lncRNAs in heart development, and highlights the usage of co-expression modular approaches in the cell-type functional definition.

bioinformatics↗

bioRxiv2021

Interleukin-10 knockout mice do not reliably exhibit macroscopic inflammation: a natural history endoscopic surveillance study

BackgroundInterleukin (IL)-10 knockout (KO) mice, used as a model for inflammatory bowel disease (IBD), develop chronic enterocolitis. Endoscopy, the gold standard for evaluation of human mucosal health, is not widely available for murine models. We aimed to assess the natural history of left-sided colitis in IL-10 KO mice via serial endoscopies. MethodsBALB/cJ IL10 KO mice underwent regular endoscopic assessments from 2 up to 8 months of age. Procedures were recorded and blindly evaluated using a 4-component endoscopic score: mucosal wall transparency, intestinal bleeding, focal lesions and perianal lesions (0-3 points each). An endoscopic score [≥]1 point was considered as the presence of colitis/flare. ResultsIL-10 KO mice (N=40, 9 female) were assessed. Mean age at first endoscopy was 62.5{+/-}2.5 days; average number of procedures per mouse was 6.0{+/-}1.3. A total of 238 endoscopies were conducted every 24.8{+/-}8.3 days, corresponding to 124.1{+/-}45.2 days of surveillance per mouse (13.6 years cumulative surveillance). Thirty-three endoscopies in 24 mice (60%) detected colitis, mean endoscopy score 2.5{+/-}1.3 (range: 1-6.3). Nineteen mice (47.5%) had one episode of colitis and 5 (12.5%) had 2-3 episodes. All exhibited complete spontaneous healing on subsequent endoscopies. ConclusionsIn this largest endoscopic surveillance study of IL-10 KO mice, 40% of mice did not develop endoscopic left-sided colitis. Furthermore, IL-10 KO mice did not exhibit persistent colitis and universally exhibited complete spontaneous healing without treatment. The natural history of colitis in IL-10 KO mice may not be comparable with that of IBD in humans and requires careful consideration.

immunology↗

bioRxiv2021

The genetic basis of tail-loss evolution in humans and apes

The loss of the tail is one of the main anatomical evolutionary changes to have occurred along the lineage leading to humans and to the "anthropomorphous apes"1,2. This morphological reprogramming in the ancestral hominoids has been long considered to have accommodated a characteristic style of locomotion and contributed to the evolution of bipedalism in humans3-5. Yet, the precise genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Primate genome sequencing projects have made possible the identification of causal links between genotypic and phenotypic changes6-8, and enable the search for hominoid-specific genetic elements controlling tail development9. Here, we present evidence that tail-loss evolution was mediated by the insertion of an individual Alu element into the genome of the hominoid ancestor. We demonstrate that this Alu element - inserted into an intron of the TBXT gene (also called T or Brachyury10-12) - pairs with a neighboring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated a mouse model that mimics the expression of human TBXT products by expressing both full-length and exon-skipped isoforms of the mouse TBXT ortholog. We found that mice with this genotype exhibit the complete absence of a tail or a shortened tail, supporting the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype, albeit with incomplete penetrance. We further noted that mice homozygous for the exon-skipped isoforms exhibited embryonic spinal cord malformations, resembling a neural tube defect condition, which affects [~]1/1000 human neonates13. We propose that selection for the loss of the tail along the hominoid lineage was associated with an adaptive cost of potential neural tube defects and that this ancient evolutionary trade-off may thus continue to affect human health today.

evolutionary biology↗

bioRxiv2021

Selection against admixture and gene regulatory divergence in a long-term primate field study

Admixture has profoundly influenced evolution across the tree of life, including in humans and other primates1,2. However, we have limited insight into the genetic and phenotypic consequences of admixture in primates, especially during its key early stages. Here, we address this gap by combining 50 years of field observations with population and functional genomic data from yellow (Papio cynocephalus) and anubis (P. anubis) baboons in Kenya, in a longitudinally studied population that has experienced both historical and recent admixture3. We use whole-genome sequencing to characterize the extent of the hybrid zone, estimate local ancestry for 442 known individuals, and predict the landscape of introgression across the genome. Despite no major fitness costs to hybrids, we identify signatures of selection against introgression that are strikingly similar to those described for archaic hominins4-6. These signatures are strongest near loci with large ancestry effects on gene expression, supporting the importance of gene regulation in primate evolution and the idea that selection targeted large regulatory effects following archaic hominin admixture7,8. Our results show that genomic data and field observations of hybrids are important and mutually informative. They therefore demonstrate the value of other primates as living models for phenomena that we cannot observe in our own lineage.

evolutionary biology↗

bioRxiv2021

Klf5 establishes bi-potential cell fate by dual regulation of ICM and TE specification genes

Early blastomeres of mouse preimplantation embryos exhibit bi-potential cell fate, capable of generating both embryonic and extra-embryonic lineages in blastocysts. Here, we identified three major 2 cell (2C) specific endogenous retroviruses (ERVs) as the molecular hallmark of the bi-potential plasticity. Using the LTRs of all three 2C-ERVs, we identified Klf5 as their major upstream regulator. Klf5 is essential for bi-potential cell fate: a single Klf5-overexpressing ESC generated terminally differentiated embryonic and extra-embryonic lineages in chimeric embryos, and Klf5 directly induces both ICM and TE specification genes. Intriguingly, Klf5 and Klf4 act redundantly during ICM specification, whereas Klf5 deficiency alone impairs TE specification. Klf5 is regulated by multiple 2C-specific transcription factors, particularly Dux, and the Dux/Klf5 axis is evolutionarily conserved. Altogether, the 2C-specific transcription program converges on Klf5 to establish bi-potential cell fate, enabling a cell state with dual activation of ICM and TE genes.

developmental biology↗

bioRxiv2021

Visualization of reactive astrocytes in living brain of Alzheimer's disease patient

An early appearance of reactive astrocytes is a hallmark of Alzheimers disease (AD)1,2, providing a substrate for early diagnostic neuroimaging targets. However, there is no clinically validated neuroimaging probe to visualize the reactive astrogliosis in the human brain in vivo. Here, we report that PET/CT imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. We demonstrate that reactive astrocytes excessively absorb acetate through elevated monocarboxylate transporter-1 (MCT1), leading to aberrant GABA synthesis and release which suppresses neuronal glucose uptake through decreased glucose transporter-3 (GLUT3) in both animal and human brains. We propose the non-invasive functional PET/CT imaging for astrocytic acetate-hypermetabolism and neuronal glucose-hypometabolism as an advanced diagnostic strategy for early stages of AD.

neuroscience↗

bioRxiv2021

Visualizing reactive astrogliosis extends survival in glioblastoma patients

Glioblastoma multiforme (GBM) is a devastating brain tumor with dismal prognosis of only 15-month survival regardless of surgical resection. Here, we report an advanced neuroimaging technique combining 11C-acetate PET and MRI (AcePET), visualizing the boundary beyond the MRI-defined tumor. Targeted biopsy of the regions with increased 11C-acetate uptake revealed the presence of reactive astrocytes with enhanced acetate-transporter MCT1, along with cancer stem cells. Reactive astrogliosis and MCT1-dependent 11C-acetate-uptake were recapitulated in U87MG-orthotopic models. Mechanistically, glycolytic tumor cells release excessive acetate causing reactive astrogliosis, leading to the release of aberrant astrocytic GABA and H2O2, which further down-regulate the neuronal glucose uptake through GLUT3. Clincally, AcePET-guided surgery allows complete tumor resection of infiltrating cancer stem cells and extends the overall survival of patients by 5.25 months compared to conventional MRI-guided surgery. We established a new concept of the metabolic interactions between GBM cells and neighboring neurons through reactive astrocytes and developed AcePET-guided surgery to fight against GBM.

cancer biology↗

bioRxiv2021

The Arabidopsis ORA59 coordinates jasmonic acid- and ethylene-responsive gene expression to regulate plant immunity

Jasmonic acid (JA) and ethylene (ET) signaling modulate plant defense against necrotrophic pathogens. These hormone pathways lead to transcriptional reprogramming, which is a major part of plant immunity and requires the roles of transcription factors. ET response factors are responsible for the transcriptional regulation of JA/ET-responsive defense genes, among which ORA59 functions as a key regulator of this process and has been implicated in the JA-ET crosstalk. Here, we identified the ERELEE4 as an ORA59-binding cis-element, in addition to the well-characterized GCC box, demonstrating that ORA59 regulates JA/ET-responsive genes through direct binding to these elements in the gene promoters. Notably, ORA59 exhibited differential preference for the GCC box and ERELEE4, depending on whether ORA59 activation is achieved by JA and ET, respectively. Our results provide insights into how ORA59 can generate specific patterns of gene expression dynamics through JA and ET hormone pathways.

plant biology↗

bioRxiv2021

Robust T1 MRI cortical surface pipeline for neonatal brain and systematic evaluation using multi-site MRI datasets

The human brain grows the most dramatically during the perinatal and early postnatal periods, during which preterm birth or perinatal injury that may alter brain structure and lead to developmental anomalies. Thus, characterizing cortical thickness of developing brains remains an important goal. However, this task is often complicated by inaccurate cortical surface extraction due to small-size brains. Here, we propose a novel complex framework for the reconstruction of neonatal WM and pial surfaces, accounting for large partial volumes due to small-size brains. The proposed approach relies only on T1-weighted images unlike previous T2-weighted image-based approaches while only T1-weighted images are sometimes available under the different clinical/research setting. Deep neural networks are first introduced to the neonatal MRI pipeline to address the mis-segmentation of brain tissues. Furthermore, this pipeline enhances cortical boundary delineation using combined models of the CSF/GM boundary detection with edge gradient information and a new skeletonization of sulcal folding where no CSF voxels are seen due to the limited resolution. We also proposed a systematic evaluation using three independent datasets comprising 736 preterm and 97 term neonates. Qualitative assessment for reconstructed cortical surfaces shows that 86.9% are rated as accurate across the three site datasets. In addition, our landmark-based evaluation shows that the mean displacement of the cortical surfaces from the true boundaries was less than a voxel size (0.532{+/-}0.035mm). Evaluating the proposed pipeline (namely NEOCIVET 2.0) shows the robustness and reproducibility across different sites and different age-groups. The mean cortical thickness measured positively correlated with postmenstrual age (PMA) at scan (p<0.0001); Cingulate cortical areas grew the most rapidly whereas the inferior temporal cortex grew the least rapidly. The range of the cortical thickness measured was biologically congruent (1.3mm at 28 weeks of PMA to 1.8mm at term equivalent). Cortical thickness measured on T1 MRI using NEOCIVET 2.0 was compared with that on T2 using the established dHCP pipeline. It was difficult to conclude that either T1 or T2 imaging is more ideal to construct cortical surfaces. NEOCIVET 2.0 has been open to the public through CBRAIN (https://mcin-cnim.ca/technology/cbrain/), a web-based platform for processing brain imaging data.

bioinformatics↗

bioRxiv2021

Mutational impact and signature of ionizing radiation

Whole-genome sequencing (WGS) of human tumors and normal cells exposed to various carcinogens has revealed distinct mutational patterns that provide deep insights into the DNA damage and repair processes. Although ionizing radiation (IR) is conventionally known as a strong carcinogen, its genome-wide mutational impacts have not been comprehensively investigated at the single-nucleotide level. Here, we explored the mutational landscape of normal single-cells after exposure to the various levels of IR. On average, 1 Gy of IR exposure generated [~]16 mutational events with a spectrum consisting of predominantly small nucleotide deletions and a few characteristic structural variations. In [~]30% of the post-irradiated cells, complex genomic rearrangements, such as chromoplexy, chromothripsis, and breakage-fusion-bridge cycles, were resulted, indicating the stochastic and chaotic nature of DNA repair in the presence of the massive number of concurrent DNA double-strand breaks. These mutational signatures were confirmed in the genomes of 22 IR-induced secondary malignancies. With high-resolution genomic snapshots of irradiated cells, our findings provide deep insights into how IR-induced DNA damage and subsequent repair processes operate in mammalian cells.

genomics↗

bioRxiv2020

Host protection to intestinal worm infections: the importance of activated and armed innate effector cells at the host parasite interface.

The intestinal roundworm Heligmosomoides bakeri causes chronic infection in susceptible (C57Bl/6) mice; however, repeat (trickle) infection confers immunity and facilitates worm clearance. We previously showed that this acquired immunity is associated with a strong Th2 response, notably the enhanced production of intestinal granulomas. Here we demonstrate that elevated proportions of IgG1-bound eosinophils and macrophages are observed around the developing tissue worms of trickle-infected female C57Bl/6 mice compared to bolus infected animals. Levels of IgG2c, IgA or IgE were not detected in the granulomas. Increased proportions of SiglecF+ and CD206+ cells, but not Ly6G+ and/or NK1.1+ cells, were also found in the granulomas of trickle-infected mice. However, in the natural world rather than the laboratory setting, immune environments are more nuanced. We examined the impact of a mixed immune environment on trickle infection-induced immunity, using a pre-infection with Toxoplasma gondii. The mixed immune environment resulted in fewer and smaller granulomas with a lack of IgG -bound cells as well as reduced proportions of SiglecF+ and CD206+ cells, measured by immunofluorescence and flow cytometry. This was associated with a higher worm burden in the co-infected animals. Our data confirm the importance of intestinal granulomas and parasite-specific antibody for parasite clearance. They highlight why it may be more difficult to clear worms in the field than in the laboratory. AUTHORS SUMMARYDespite decades of research on intestinal parasitic worms, we are still unable to clearly point to why so many people (approximately 1.8 billion) and most livestock/wild animals are infected with these parasites. We have made progress in understanding how the immune system responds to parasitic worms, and how these parasites manipulate our immune system. However, identifying effective clearance mechanisms is complex and context dependent. We have used models of trickle infection (multiple low doses of parasites) and co-infection (two intestinal parasites) to simulate how people/animals get infected in the real world. Using these models, we have confirmed the host/parasite interface (the granuloma) within the intestinal tissue to be key in determining the hosts ability to clear worms. The lack of specific immune cells and antibodies within the granuloma was associated with chronic infection. Our results help explain why intestinal parasitic worms are so prevalent and why it may be difficult to clear worms in natural settings.

immunology↗

bioRxiv2020

Clonal dynamics in early human embryogenesis inferred from somatic mutation

The trillions of cells that constitute the human body are developed from a fertilized egg through embryogenesis. However, cellular dynamics and developmental outcomes of embryonic cells in humans remain to be largely unknown due to the technical and ethical challenges. Here, we explored whole-genomes of 334 single-cell expanded clones and targeted deep-sequences of 379 bulk tissues obtained from various anatomical locations from seven individuals. Using the discovered 1,688,652 somatic mutations as an intrinsic barcode, we reconstructed cellular phylogenetic trees that provide novel insights into early human embryogenesis. Our findings suggest (1) endogenous mutational rate that is higher in the first cell division of life but decreases to ~1 per cell per cell division later in life, (2) universal unequal contribution of early cells into embryo proper resulting from early cellular bottlenecks that stochastically separate epiblasts from embryonic cells (3) uneven differential outcomes of early cells into three germ layers, left-right and cranio-caudal tissues, (4) emergence of a few ancestral cells that will contribute to the substantial fraction of adult blood cells, and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach additionally provides insights into the age-related mutational processes including UV-mediated mutagenesis and loss of chromosome X or Y in normal somatic cells. Taken together, this study scrutinized somatic mosaicism, clonal architecture, and cellular dynamics in human embryogenesis at an unprecedented level and provides a foundation for future studies to complete cellular phylogenies in human embryogenesis.

genomics↗

bioRxiv2020

A cross-species drug discovery pipeline to identify and validate new treatments for osteosarcoma

PurposeOsteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new treatments has been hampered by extensive genomic heterogeneity and limited access to patient samples to study the biology of this complex disease. Experimental designTo overcome these barriers, we combined the power of comparative oncology with patient-derived models of cancer and high-throughput chemical screens in a cross-species drug discovery pipeline. ResultsCoupling in vitro high-throughput drug screens on low-passage and established cell lines with in vivo validation in patient-derived xenografts we identify the proteasome and CRM1 nuclear export pathways as therapeutic sensitivities in osteosarcoma, with dual inhibition of these pathways inducing synergistic cytotoxicity. ConclusionsThese collective efforts provide an experimental framework and set of new tools for osteosarcoma and other rare cancers to identify and study new therapeutic vulnerabilities.

cancer biology↗

bioRxiv2020

Medial prefrontal cortex has a causal role in selectively enhanced consolidation of emotional memories after a 24-hour delay: An iTBS study

Previous research points to an association between retrieval-related activity in the medial prefrontal cortex (mPFC) and preservation of emotional information compared to co-occurring neutral information following sleep. Although the role of the mPFC in emotional memory likely begins at encoding, little research has examined how mPFC activity during encoding interacts with consolidation processes to enhance emotional memory. This issue was addressed in the present study using transcranial magnetic stimulation in conjunction with an emotional memory paradigm. Healthy young adults encoded negative and neutral scenes while undergoing concurrent TMS with a modified short intermittent theta burst stimulation (sTBS) protocol. Participants received stimulation to either the mPFC or an active control site (motor cortex) during the encoding phase. Recognition memory for scene components (objects and backgrounds) was assessed after a short (30-minute) and a long delay (24-hour, including a night of sleep) to obtain measures of specific and gist-based memory processes. The results demonstrated that, relative to control stimulation, sTBS to the mPFC enhanced memory for negative objects on the long delay test (collapsed across specific and gist-based memory measures). mPFC stimulation had no discernable effect on memory for objects on the short delay test nor on the background images at either test. These results suggest that mPFC activity occurring during encoding interacts with consolidation processes to preferentially preserve negatively salient information. Significance StatementUnderstanding how emotional information is remembered over time is critical to understanding memory in the real world. The present study used noninvasive brain stimulation (repetitive transcranial magnetic stimulation, rTMS) to investigate the interplay between mPFC activity that occurs during memory encoding and its subsequent interactions with consolidation processes. rTMS delivered to the mPFC during encoding enhanced memory for negatively valenced pictures on a test following a 24-hr delay, with no such effect on a test occurring shortly after the encoding phase. These results are consistent with the hypothesis that emotional aspects of memories are differentially subjected to consolidation processes, and that the mPFC might contribute to this "tag-and-capture" mechanism during the initial formation of such memories.

neuroscience↗

bioRxiv2020

Hericerin derivatives from Hericium erinaceus exert BDNF-like neurotrophic activity in central hippocampal neurons and enhance memory

The traditional medicinal mushroom Hericium erinaceus has long been known for enhancing the peripheral nerve regeneration through targeting nerve growth factor (NGF) neurotrophic activity. It was also reported to protect against ageing-dependent cognitive decline in wildtype and in Alzheimers disease mouse models suggesting a yet to be defined action on neurons of the central nervous system. Here, we purified and identified biologically active compounds from H. erinaceus, based on their ability to promote neurite outgrowth in hippocampal neurons. N-de phenylethyl isohericerin (NDPIH), an isoindoline compound from this mushroom together with its hydrophobic derivative hericene A, were highly potent in inducing extensive axon outgrowth and neurite branching in the absence of serum demonstrating high neurotropic activity. NDPIH also induced enlarged growth cones suggestive of a brain-derived neurotrophic factor (BDNF)-like activity. Pharmacological inhibition of tropomyosin receptor kinase B (TrkB) by ANA12 prevented NDPIH-induced neurotrophic activity providing evidence that NDPIH acts via TrkB receptors to mediate its neurotrophic effect in central neurons. Finally, in vivo treatment with H. erinaceus crude extract and hericene A significantly increased BDNF and downstream pathway and enhanced learning and memory in the novel object recognition memory test. Our results suggest that hericene A can promote BDNF-like activity in neurons in vitro and in vivo thereby enhancing recognition memory.

neuroscience↗