High Behavioral Reactivity to Novelty as a Susceptibility Factor for Memory and Anxiety Disorders in Streptozotocin-Induced Neuroinflammation as a Rat Model of Alzheimer’s Disease

Individual differences in responsiveness to environmental factors, including stress reactivity and anxiety levels, which differ between high (HR) and low (LR) responders to novelty, might be risk factors for development of memory and anxiety disorders in sporadic Alzheimer's disease (sAD). In the present study, we investigated whether behavioral characteristics of the HR and LR rats, influence the progression of sAD (neuroinflammation, β-amyloid peptide, behavioral activity related to memory (Morris water maze) and anxiety (elevated plus maze, white and illuminated open field test) in streptozotocin (STZ)-induced neuroinflammation as a model of early pathophysiological alterations in sAD. Early (45 days) in disease progression, there was a more severe impairment of reference memory and higher levels of anxiety in HRs compared with LRs. Behavioral depression in HRs was associated with higher expression of β-amyloid deposits, particularly in the NAcS, and activation of microglia (CD68⁺ cells) in the hypothalamus, as opposed to less inflammation in the hippocampus, particularly in CA1, compared with LRs in late (90 days) sAD progression. Our findings suggest that rats with higher behavioral activity and increased responsivity to stressors show more rapid progression of disease and anxiety disorders compared with low responders to novelty in the STZ-induced sAD model.