Biology subjects

Park, H. W.

Publications and source records attributed to Park, H. W..

3 recordsLinked to original sources

bioRxiv2024

Robust Methods For Quantifying Neuronal Morphology And Molecular Signaling Reveal That Psychedelics Do Not Induce Neuroplasticity

Induction of neuroplasticity has become the dominant explanatory framework for the rapid and sustained therapeutic effects of classic psychedelics. Within this broad concept, examination of morphological neuronal plasticity, such as dendritic arbor growth, is widely used to assess the neuroplasticity effects of classic and novel psychedelics. At the molecular level, it has been reported that serotonergic psychedelic compounds mediate dendritogenesis via the master molecular regulator of plasticity, TrkB, either directly via BDNF/TrkB signaling potentiation or indirectly through 5-HT2A receptor. To examine these hypotheses in detail, we developed a robust multimodal screening platform for unbiased, semi-automated quantification of cellular morphology and multiplex molecular signaling in the same cortical neurons. We found that in widely used primary neuronal cultures psychedelics do not directly modulate TrkB receptor or BDNF-TrkB signaling. We also found 5HT2a receptor gene expression and functional receptor levels are low, and psychedelics do not induce morphological growth, in contrast to significant dendritogenesis elicited by BDNF. Our results challenge recently published results in the field and indicate a need for rigorous experimental methods to study morphological manifestations of neuroplasticity effects induced by clinically used and experimental therapeutics.

neuroscience↗

bioRxiv2023

Beclin1-Deficient Adipocytes Promote Tumor Progression by YAP/TAZ-dependent Adipocyte Transformation

Adipocytes are crucial components of the tumor microenvironment (TME) that play a prominent role in supporting tumor growth. However, the characteristics of cancer-associated adipocytes (CAAs) that contribute to the pro-tumorigenic niche remain to be fully established. Here, we used adipocyte-specific Beclin1 KO (BaKO) mice to investigate the role of maladaptive adipocytes in promoting tumor progression. BECN1-deficient adipocytes exhibited downregulation of adipogenic markers and activation of YAP/TAZ signaling, similar to the traits observed in CAAs. Thus, we generated adipocyte-specific Becn1/Yap1/Taz KO mice, which exhibit markedly restored phenotypes in adipose tissue, resulting in tumor regression compared to that in BaKO. Further, we observed dysregulation of the BECN1-YAP/TAZ axis in the adipose tissue of mice fed a high-fat diet (HFD). Treatment with the YAP/TAZ inhibitor, verteporfin, suppressed tumor progression in BaKO and HFD-fed mice, highlighting its efficacy against mice with metabolic dysregulation. Our findings provide insights into CAA formation and its significance in determining malignant TME, thereby suggesting a potential dual therapeutic strategy simultaneously targeting adipocyte homeostasis and cancer growth.

biochemistry↗

bioRxiv2023

Previous breeding success and carrion substrate together influence subsequent carrion choice by adult Nicrophorus vespilloides

Insects can adjust their behaviour in relation to experience in a wide range of contexts including foraging, mate selection, and choice of oviposition site. Here we investigate whether burying beetles modulate their choice of carrion in relation to the outcome of their past breeding experience. Burying beetles require small vertebrate carrion to reproduce. Beetle parents convert carrion into an edible nursery for their larvae, whom they typically care for throughout larval development. We tested whether a beetles past breeding experience influenced its subsequent choice of carrion, when presented simultaneously with either a dead mouse or a dead chick. We found that both male and female beetles favoured the same carrion as used in their first breeding attempt - but only if they had produced many larvae and only if they had previously bred on a mouse. Beetles that had produced fewer larvae on a dead mouse switched to favouring dead chicks in their second breeding attempt. Those that had bred on a dead chick chose carrion at random subsequently, regardless of their previous breeding success. Our general conclusion is that burying beetles can integrate different sources of information about their past breeding experience with current cues when selecting carrion for reproduction.

evolutionary biology↗