Dataset Information

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. Down-regulation of BDNF is correlated with increased severity of HIV/neuroAIDS. BDNF-CT enhanced neurorestorative effects in the hippocampus including newborn cell proliferation and survival, granule cell neurogenesis, synaptogenesis and increased dendritic integrity. BDNF-CT exerted cognitive-enhancing effects by reducing Tat-induced learning and memory deficits. These results show that CT bionanoparticles efficiently deliver BDNF to the brain, making them potentially powerful tools in regenerative medicine.

SUBMITTER: Vitaliano GD

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

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Vitaliano Gordana D GD Kim Jae K JK Kaufman Marc J MJ Adam Christopher W CW Zeballos Gonzalo G Shanmugavadivu Abinaya A Subburaju Sivan S McLaughlin Jay P JP Lukas Scott E SE Vitaliano Franco F

Communications biology 20220317 1

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 w ...[more]

PMID: 35301411

Similar Datasets

Project description:BackgroundAdult-onset stressors exert opposing effects on hippocampal neurogenesis and cognition, with enhancement observed following mild stress and dysfunction following severe chronic stress. While early life stress evokes persistent changes in anxiety, it is unknown whether early stress differentially regulates hippocampal neurogenesis, trophic factor expression, and cognition across the life span.MethodsHippocampal-dependent cognitive behavior, neurogenesis, and epigenetic regulation of brain-derived neurotrophic factor (Bdnf) expression was examined at distinct time points across the life span in rats subjected to the early stress of maternal separation (ES) and control groups. We also examined the influence of chronic antidepressant treatment on the neurogenic, neurotrophic, and cognitive changes in middle-aged ES animals.ResultsAnimals subjected to early stress of maternal separation examined during postnatal life and young adulthood exhibited enhanced hippocampal neurogenesis, decreased repressive histone methylation at the Bdnf IV promoter along with enhanced BDNF levels, and improved performance on the stress-associated Morris water maze. Strikingly, opposing changes in hippocampal neurogenesis and epigenetic regulation of Bdnf IV expression, concomitant with impairments on hippocampal-dependent cognitive tasks, were observed in middle-aged ES animals. Chronic antidepressant treatment with amitriptyline attenuated the maladaptive neurogenic, epigenetic, transcriptional, and cognitive effects in middle-aged ES animals.ConclusionsOur study provides novel insights into the short- and long-term consequences of ES, demonstrating both biphasic and unique, age-dependent changes at the molecular, epigenetic, neurogenic, and behavioral levels. These results indicate that early stress may transiently endow animals with a potential adaptive advantage in stressful environments but across a life span is associated with long-term deleterious effects.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets