Alzheimer's disease (AD) patients frequently experience neuropsychiatric symptoms (NPS), which are linked to a lower quality of life and a faster rate of disease progression. A growing body of research indicates that several microglial phenotypes control the inflammatory response and are crucial in the pathophysiology of AD-related NPS. Given the crucial role played by inflammatory mediators produced by microglia in developing of NPS, interferon-beta (IFNβ), a cytokine with anti-inflammatory capabilities, maybe a successful treatment for NPS caused by AD. In this investigation, using a rat model of AD, we examined the impact of intranasal treatment of IFNβ on anxious/depressive-like behavior and microglial M1/M2 polarization. The rat hippocampus was bilaterally injected with lentiviruses harboring mutant human amyloid precursor protein. Rats were given recombinant IFNβ1a (68,000 IU/rat) via the intranasal route, starting on day 23 following viral infection and continuing until day 49. On days 47-49, the elevated plus maze, forced swim, and tail suspension tests were applied to measure anxiety- and depressive-like behavior. Additionally, qPCR was utilized to quantify the expression of M1 markers (CD68, CD86, and CD40) and M2 markers (Ym1, CD206, Arg1, GDNF, BDNF, and SOCS1). Our findings demonstrated that decreased M2 marker expression is accompanied by anxious/depressive-like behavior when the mutant human APP gene is overexpressed in the hippocampus. In the rat model of AD, IFNβ therapy reduces anxious/depressive-like behaviors, at least in part by polarizing microglia towards M2. Therefore, IFNβ may be a viable therapeutic drug for reducing NPS in the context of AD.
Keywords: Alzheimer’s disease; Anxiety; Depression; Interferon-beta; Microglia; Polarization.
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