Intranasal interferon beta improves memory and modulates inflammatory responses in a mutant APP-overexpressing rat model of Alzheimer's disease.

This study aimed to answer if the intranasal (IN) administration of IFNβ with high CNS accessibility can alleviate memory impairments in a mutant APP-overexpressing rat model of AD through modulating inflammatory responses. To address this question, the lentiviruses carrying human amyloid protein precursor (APP) with the Swedish and Indiana mutations (LV-APPSw/Ind) were bilaterally injected in the hippocampus of adult rats. Memory performance was assessed using passive avoidance task on days 49 and 50 after injection. Moreover, the expression of glial markers (GFAP and Iba1) and pro-inflammatory (TNF-α, IL-1β and IL-6) and anti-inflammatory cytokines (IL-10) were evaluated in the hippocampus. Therapeutic effects of IN-administered IFNβ (0.5 μg/kg and 1 μg/kg doses, every other day from day 23 to 50 after lentivirus injection) were examined in the LV-APP-injected rats. Our results showed that over-expression of mutant human APP gene in the hippocampus led to learning and memory deficits concomitant with gliosis and pro-inflammatory responses. Interestingly, treatment of AD-modeled rats with IFNβ ameliorated memory impairments possibly through suppressing gliosis and shifting from pro-inflammatory toward anti-inflammatory status, suggesting that IFNβ may be a promising therapeutic agent to improve cognitive functions and modulate inflammatory responses in an AD-like neurodegenerative context. PMID: 31233762 [PubMed - as supplied by publisher]
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research