Clathrin-nanoparticles deliver BDNF to hippocampus and enhance neurogenesis, synaptogenesis and cognition in HIV/neuroAIDS mouse model.

ABSTRACT: Brain derived neurotrophic factor (BDNF) promotes the growth, differentiation, maintenance and survival of neurons. These attributes make BDNF a potentially powerful therapeutic agent. However, its charge, instability in blood, and poor blood brain barrier (BBB) penetrability have impeded its development. Here, we show that engineered clathrin triskelia (CT) conjugated to BDNF (BDNF-CT) and delivered intranasally increased hippocampal BDNF concentrations 400-fold above that achieved previously with intranasal BDNF alone. We also show that BDNF-CT targeted Tropomyosin receptor kinase B (TrkB) and increased TrkB expression and downstream signaling in iTat mouse brains. Mice were induced to conditionally express neurotoxic HIV Transactivator-of-Transcription (Tat) protein that decreases BDNF.

SUBMITTER: Vitaliano GD 

PROVIDER: S-EPMC8931075 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature