Effect of intrananasally administered deferoxamine in the intracerebroventricular streptozotocin rat model of Alzheimer's disease

Intranasal (IN) deferoxamine (DFO) has emerged over the past decade as a promising therapeutic in preclinical experiments across neurodegenerative and neurovascular diseases. As an antioxidant iron chelator, its mechanisms are multimodal, involving the binding of brain iron and the consequent engagement of several pathways to counter pathogenesis across multiple diseases. We and other research groups have shown that IN DFO rescues cognitive impairment in several rodent models of Alzheimer Disease (AD). This study was designed to probe dosing regimens to inform future clinical trials, while exploring mechanisms within the intracerebroventricular (ICV) streptozotocin (STZ) model. Using RNA-sequencing and pathway analysis, STZ was shown to induce several pathways of cell death and neuroinflammation, and IN DFO engaged multiple transcriptomic pathways involved in hippocampal neuronal survival. To our knowledge this study is the first to assess the transcriptomic pathways and mechanisms associated with either the ICV STZ model or DFO treatment, and the first to demonstrate efficacy at this low dose. To determine effects of both IN DFO and ICV STZ on RNA-sequencing pathways in rat brain tissue, rats were first sibjected to either a sham surgery or ICV-STZ injection to induce the model. They were then treated intranasally with either saline or a 1% solution of DFO. Their brains were collected and analyses with RNA-sequencing.