Project description:Silkworms show a reproductive behavior induced by sex pheromone. To elucidate the neral mechanism of sex pheromone induced sexual behavior in the silkworm, we attempted to use the neural activity-induced gene as a neural activity marker. Since no neural activity-induced gene was identified in the silkworm, we conducted screening of neural activity-induced gene using the male silkworm brain. By the screening, we identified Bhr38 as a novel neural activity-induced gene, and succeded to comprehensively map the active neruons in the silkworm brain in response to the sex pheromone exposure. Further, we found that Dhr38, the Drosophila homologue of Bhr38, also expressed in a neural activity dependent manner. These results strongly suggest that Hr38 is a highly conserved neural activity-induced gene. The male silkworms were exposed to the female odor for 30 min (group P). Non-treated male silkworms were used as the control group group C. Ten brains were collected for each sample and stored at -80°C until use. Total RNA was isolated by the TRIzol reagent and subjected to microarray experiments using the custam made (8x16k) Oligo Microarray (Agilent Technologies, Inc.).
Project description:Silkworms show a reproductive behavior induced by sex pheromone. To elucidate the neral mechanism of sex pheromone induced sexual behavior in the silkworm, we attempted to use the neural activity-induced gene as a neural activity marker. Since no neural activity-induced gene was identified in the silkworm, we conducted screening of neural activity-induced gene using the male silkworm brain. By the screening, we identified Bhr38 as a novel neural activity-induced gene, and succeded to comprehensively map the active neruons in the silkworm brain in response to the sex pheromone exposure. Further, we found that Dhr38, the Drosophila homologue of Bhr38, also expressed in a neural activity dependent manner. These results strongly suggest that Hr38 is a highly conserved neural activity-induced gene.
Project description:Neuronal activity-dependent gene expression plays important roles in neural plasticity. We use electroconvulsive stimulation (ECS) as an in vivo model for neuronal activation to identify genes that are regulated by neuronal activity. Dentate gyri (DG) were microdissected 4 hours after sham or ECS treatment for gene expression profiling. 4 total samples were analysed (2 for each condition). Averaged expression values between sham and ECS samples were pair-wise compared.
Project description:Neuronal activity-dependent gene expression plays important roles in neural plasticity. We use electroconvulsive stimulation (ECS) as an in vivo model for neuronal activation to identify genes that are regulated by neuronal activity. Dentate gyri (DG) were microdissected 4 hours after sham or ECS treatment for gene expression profiling.
Project description:The neural behavior of glioblastoma, including the formation of tumor microtubes and synaptic circuitry, is increasingly understood to be pivotal for disease manifestation (Osswald et al. 2015; Venkatesh et al. 2015; Weil et al. 2017; Venkataramani et al. 2019; Venkatesh et al. 2019; Alcantara Llaguno et al. 2019; Venkataramani et al. 2022). Nonetheless, the few approved treatments for glioblastoma target its oncological nature, while its neural vulnerabilities remain incompletely mapped and clinically unexploited. Here, we systematically survey the neural molecular dependencies and cellular heterogeneity across 27 glioblastoma patients and diverse model systems. In patient tumor samples taken directly after surgery, we identify a spectrum of neural stem cell morphologies indicative of poor prognosis, and discover a set of repurposable neuroactive drugs with unexpected and consistent anti-glioma efficacy. Glioblastoma cells exhibit functional dependencies on highly expressed drug targets including neurological ion channels and receptors, while interpretable molecular machine learning reveals downstream convergence on secondary drug targets (COSTAR) involving AP-1-driven tumor suppression. COSTAR enables in silico drug screening on >1 million compounds that are validated with high accuracy. Multi-omic profiling of drug-treated glioblastoma cells confirms rapid Ca2+-driven AP-1 pathway induction to represent a tumor-intrinsic vulnerability at the intersection of oncogenesis and neural activity-dependent signaling. Finally, the consistent anti-glioma activity across patients and model systems is epitomized by the antidepressant Vortioxetine, which synergizes in vivo with approved glioblastoma chemotherapies. In all, our global analysis reveals that the neural vulnerabilities of glioblastoma converge on an AP-1 mediated gene regulatory network with direct translatable potential.
Project description:Human induced pluripotent stem cells (hiPSCs) have emerged as a promising in vitro model system for studying neurodevelopment. However, current models remain limited in their ability to incorporate tunable biochemical and biomechanical signaling cues imparted by the neural extracellular matrix (ECM). The native brain ECM is viscoelastic and stress-relaxing, exhibiting a time-dependent response to an applied force. To recapitulate the remodelability of the neural ECM, we developed a family of protein-engineered hydrogels crosslinked with either static or dynamic covalent bonds that exhibit tunable stress relaxation rates. hiPSC-derived neural progenitor cells (NPCs) encapsulated within these gels underwent relaxation rate-dependent maturation. Specifically, NPCs within hydrogels with faster stress relaxation rates extended longer, more complex neuritic projections, exhibited decreased metabolic activity, and expressed higher levels of genes associated with neural maturation. By inhibiting actin polymerization, we observed decreased neuritic projections and a concomitant decrease in the expression of neural maturation genes. Taken together, these results suggest that microenvironmental viscoelasticity is sufficient to bias human NPC maturation.