A Window to the Brain: The Retina to Monitor the Progression and Efficacy of Saffron Repron® Pre-Treatment in an LPS Model of Neuroinflammation and Memory Impairment

Abstract

A mechanism shared by most neurodegenerative diseases, like Alzheimer’s disease (AD) and Parkinson’s disease (PD), is neuroinflammation. It has been shown to have a link between cognitive impairment and retinal function under neuroinflammatory conditions, confirming the essential role of the retina as a window to the brain. Here, we characterize a mouse model of LPS-induced neuroinflammation describing the parallel deterioration of both memory and visual function. Then, we demonstrate, using the Novel Object Recognition test (NOR) and electroretinogram (ERG) recordings, that preventive, chronic treatment with saffron Repron® is able to reduce the neuroinflammation process and prevent the impairment of both cognitive and visual function. The improvement in behavioral and visual function is confirmed by the pattern of expression of neuroinflammation-related genes and related proteins where pre-treatment with Repron® saffron presents a positive modulation compared with that obtained in animals treated with LPS alone. These results hold for retinal tissue and partially in the brain, where it appears that the onset of damage was delayed. This trend underlines the critical role of the retina as a most sensitive portion of the central nervous system to LPS-induced damage and could be used as a “sensor” for the early detection of neurodegenerative diseases such as Alzheimer’s.

A novel Mediterranean diet-inspired supplement ameliorates cognitive, microbial, and metabolic deficits in a mouse model of low-grade inflammation

“…We have previously utilized this model and described similar defects in recognition memory. 13 In comparison to other studies, a onetime 0.33 mg/kg administration did not detect spatial memory impairment in young mice, 46 and 5 days of 0.25 mg/kg treatment resulted in reduced NOR performance, 15 reporting on no other behavioral changes (no others measured). Administration of 0.25–0.75 mg/kg for 7 sequential days appears to consistently induce cognitive decline across a broad range of cognitive domains, 47–50 with reduced spatial and recognition memory reported (Morris water maze, y maze NOR) however OF performance was only quantified (and found to be influenced by LPS) by Oz et al 50 Similar results were also reported in a study in which the seven injections were administered on alternative days (Water maze and Y maze), 51 again OF was not reported.…”

“…Similarly, it has been reported that the Mediterranean diet, 21 as well as its bioactive constituents, 22 can mitigate inflammation, leading to improvements in cognition and recognition memory alike. 15 , 23–25 It is likely that the anti-inflammatory actions of Neurosyn240 contribute to this effect, however this is difficult to establish as the intervention is a low-grade inflammation and thus sub-clinical inflammatory response as described by our group previously. 13 However, analysis at the gene level provides insight into this process (Supplementary Figure S6), with neurosyn240 displaying anti-inflammatory effects in both the colon and the brain.…”