Interferon beta attenuates recognition memory impairment and improves brain glucose uptake in a rat model of Alzheimer's disease: Involvement of mitochondrial biogenesis and PI3K pathway

Abstract

Interferon beta (IFNβ) is a cytokine with anti-apoptotic and anti-inflammatory properties, and its beneficial effects on Alzheimer's disease (AD) have been recently shown. The alterations in cerebral glucose uptake are closely linked to memory deficit and AD progression. The current study was designed to determine if IFNβ can improve recognition memory and brain glucose uptake in a rat model of AD. The lentiviruses expressing mutant human amyloid precursor protein were injected bilaterally to the rat hippocampus. From day 23 after virus injection, rats were intranasally treated with recombinant IFNβ protein (68,000 IU/rat) every other day until day 50. Recognition memory performance was evaluated by novel object recognition test on days 46–49. The 18F-2- fluoro-deoxy-d-glucose positron emission tomography (18F-FDG-PET) was used to determine changes in brain glucose metabolism on day 50. The expression of the PI3K/Akt pathway components, neurotrophins and mitochondrial biogenesis factors were also measured by qPCR in the hippocampus. Our results showed that IFNβ treatment improves recognition memory performance in parallel with increased glucose uptake and neuronal survival in the hippocampus of the AD rats. The neuroprotective effect of IFNβ could be attributed, at least partly, to activation of PI3K-Akt-mTOR signaling pathway, increased expression of NGF, and mitochondrial biogenesis. Taken together, our findings suggest the therapeutic potential of IFNβ for AD.