He You

All Publications

• Inhibiting proBDNF to mature BDNF conversion leads to ASD-like phenotypes in vivo. Molecular psychiatry Yang, F., You, H., Mizui, T., Ishikawa, Y., Takao, K., Miyakawa, T., Li, X., Bai, T., Xia, K., Zhang, L., Pang, D., Xu, Y., Zhu, C., Kojima, M., Lu, B. 2024

  Abstract

  Autism Spectrum Disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is regulated by mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF in a diametrically opposite manner: proBDNF inhibits while mBDNF potentiates synapses. Here we generated a knock-in mouse line (BDNFmet/leu) in which the conversion of proBDNF to mBDNF is attenuated. Biochemical experiments revealed residual mBDNF but excessive proBDNF in the brain. Similar to other ASD mouse models, the BDNFmet/leu mice showed reduced dendritic arborization, altered spines, and impaired synaptic transmission and plasticity in the hippocampus. They also exhibited ASD-like phenotypes, including stereotypical behaviors and deficits in social interaction. Moreover, the plasma proBDNF/mBDNF ratio was significantly increased in ASD patients compared to normal children in a case-control study. Thus, deficits in proBDNF to mBDNF conversion in the brain may contribute to ASD-like behaviors, and plasma proBDNF/mBDNF ratio may be a potential biomarker for ASD.

  View details for DOI 10.1038/s41380-024-02595-5

  View details for PubMedID 38762692

• Regulation of Satiety by <i>Bdnf</i>-<i>e2</i>-Expressing Neurons through TrkB Activation in Ventromedial Hypothalamus BIOMOLECULES Chu, P., Guo, W., You, H., Lu, B. 2023; 13 (5)

  Abstract

  The transcripts for Bdnf (brain-derived neurotrophic factor), driven by different promoters, are expressed in different brain regions to control different body functions. Specific promoter(s) that regulates energy balance remain unclear. We show that disruption of Bdnf promoters I and II but not IV and VI in mice (Bdnf-e1-/-, Bdnf-e2-/-) results in obesity. Whereas Bdnf-e1-/- exhibited impaired thermogenesis, Bdnf-e2-/- showed hyperphagia and reduced satiety before the onset of obesity. The Bdnf-e2 transcripts were primarily expressed in ventromedial hypothalamus (VMH), a nucleus known to regulate satiety. Re-expressing Bdnf-e2 transcript in VMH or chemogenetic activation of VMH neurons rescued the hyperphagia and obesity of Bdnf-e2-/- mice. Deletion of BDNF receptor TrkB in VMH neurons in wildtype mice resulted in hyperphagia and obesity, and infusion of TrkB agonistic antibody into VMH of Bdnf-e2-/- mice alleviated these phenotypes. Thus, Bdnf-e2-transcripts in VMH neurons play a key role in regulating energy intake and satiety through TrkB pathway.

  View details for DOI 10.3390/biom13050822

  View details for Web of Science ID 000995635100001

  View details for PubMedID 37238691

  View details for PubMedCentralID PMC10216274

• A protocol for establishing a male GxE schizophrenia mouse model STAR PROTOCOLS Zhang, T., Li, S., Mei, F., You, H., Chen, Y., Yang, F., Li, B. 2022; 3 (4): 101856

  Abstract

  Schizophrenia pathogenesis involves both genetic and environmental factors (G×E). Here, we present a protocol to prepare a schizophrenia rodent model with a specific G×E pair. We describe the breeding of Bdnf-e6-/- mice with genetic deficiency in promoter-VI-driven BDNF expression. We then detail the procedure to expose the mice to postnatal environmental stress including hypoxia, social isolation, and corticosterone. This model better represents the etiology of schizophrenia and thus may facilitate basic research and drug development for schizophrenia. For complete details on the use and execution of this protocol, please refer to Chen et al. (2022).1.

  View details for DOI 10.1016/j.xpro.2022.101856

  View details for Web of Science ID 001060309600001

  View details for PubMedID 36595927

  View details for PubMedCentralID PMC9676628

• Engineering a Magnetic Protein Crystal Li, T., Wang, Z., You, H., Ong, Q., Varanasi, V., Dong, M., Lu, B., Pasca, S., Cui, B. CELL PRESS. 2020: 153A

  View details for Web of Science ID 000513023201017

• Engineering a Genetically Encoded Magnetic Protein Crystal. Nano letters Li, T. L., Wang, Z., You, H., Ong, Q., Varanasi, V. J., Dong, M., Lu, B., Pasca, S. P., Cui, B. 2019

  Abstract

  Magnetogenetics is a new field that leverages genetically encoded proteins and protein assemblies that are sensitive to magnetic fields to study and manipulate cell behavior. Theoretical studies show that many proposed magnetogenetic proteins do not contain enough iron to generate substantial magnetic forces. Here, we have engineered a genetically encoded ferritin-containing protein crystal that grows inside mammalian cells. Each of these crystals contains more than 10 million ferritin subunits and is capable of mineralizing substantial amounts of iron. When isolated from cells and loaded with iron in vitro, these crystals generate magnetic forces that are 9 orders of magnitude larger than the forces fromthe single ferritin cages used in previous studies. These protein crystals are attracted to an applied magnetic field and move toward magnets even when internalized into cells. While additional studies are needed to realize the full potential of magnetogenetics, these results demonstrate the feasibility of engineering protein assemblies for magnetic sensing.

  View details for DOI 10.1021/acs.nanolett.9b02266

  View details for PubMedID 31552740