L‐arginine mitigates choroid plexus changes in Alzheimer’s disease rat model via oxidative/inflammatory burden and behavioral modulation

Abstract

Aging is a risk factor for Alzheimer’s disease (AD), leading to choroid plexus (CP) alterations. This study aimed to explore the possible therapeutic mechanisms of ARG on AD-induced CP changes. Sprague-Dawley rats were divided into 6 groups (n = 7 per group): adult, adult+ARG, aged, aged+ARG, aged+AD, and aged+AD+ARG groups. Evaluations were for Y-maze test, serum levels of oxidative/inflammatory markers, and serum and cerebrospinal fluid (CSF) markers of AD, histopathology, immunohistochemistry, and histomorphometry. The aged+AD group demonstrated a significant decline in maze test parameters, total antioxidant capacity (TAC), brain-derived neurotrophic factor (BDNF) levels, and vascular endothelial growth factor (VEGF) immunoexpression, while tumour necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), beta-amyloid (Aβ) levels and amyloid protein precursor (APP), and heat shock protein90 (HSP90) immunoexpressions were significantly increased. Sections of this group showed flat epitheliocytes, congested capillaries, connective tissue expansion, and degenerated endothelium. These parameters were modulated by ARG administration, via increased levels of TAC (1.37 vs 2.17 mmol/L), (p = 0.018) BDNF (serum: 48.50 vs 78.41; CSF: 4.07 vs 7.11 pg/ml) (p< 0.001), and VEGF (0.07 vs 0.26 OD) (p< 0.001), in addition to decreased levels of TNF-α (86.63 vs 41.39 pg/ml) (p< 0.001), IL-1β (96.04 vs 39.57 pg/ml) (p< 0.001), Aβ (serum: 67.40 vs 47.30; CSF: 189.26 vs 169.84 pg/ml) (p< 0.001), and HSP90 (0.54 vs 0.13 OD) (p< 0.001). In conclusion, ARG ameliorates the AD-associated CP changes, including histopathological, oxidative/inflammatory, and AD markers, and VEGF and HSP90 immunohistochemical alterations. Dietary ARG consumption is recommended to avoid AD progression in the elderly.