Abscisic acid ameliorates cognitive deficits in an amyloid-β-induced mouse model of Alzheimer's disease associated with alterations in markers of neuroplasticity and neuroinflammation.

Abscisic acid (ABA, C15H20O4), a mammalian hormone, exhibits neuroprotective and anti-inflammatory properties. This study aimed to investigate the effects of ABA on the hippocampal-dependent processes: anxiety-, depression-like behaviors and cognitive impairments as well as levels of factors involved in neuroplasticity and neuroinflammation in an amyloid-β (Aβ)-induced mouse model of Alzheimer's disease (AD). One week following intracerebroventricular (i.c.v.) injection of Aβ1-42 in male mice, ABA was administered i.c.v. at doses of 10 or 15 µg/µl for 7 consecutive days. Behavioral assessments were conducted using the novel object recognition, open field, elevated plus maze, tail suspension, Morris water maze, and passive avoidance tests. Hippocampal gene expression levels of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor (NMDAR), and nuclear factor-κB (NF-κB) were evaluated using real-time PCR. ABA treatment significantly attenuated anxiety-like behaviors and improved spatial, avoidance and recognition memory deficits induced by Aβ1-42 administration with more behavioral domains affected at the 15  µg/µl dose. ABA induced significant upregulation in the hippocampus of NMDAR and BDNF expression and marked suppression of NF-κB in the ABA (15 µg/µl)-treated Aβ group, which could have played a mechanistic role in improvements in behaviors controlled by this structure. Histological analysis demonstrated attenuation of neuronal degeneration and pyknosis in the hippocampal CA1 region following ABA intervention. Collectively, these findings suggest that ABA ameliorates anxiety-related behaviors and cognitive impairments in an experimental mouse model of AD, potentially through modulation of neuroinflammatory and neuroplasticity-related pathways.