Effects of Rosmarinic Acid on L‐Methionine‐Induced Behavioral Impairments and Disruptions in Hippocampal Neurogenesis in the Adult Rat

ABSTRACT L‐methionine (L‐met) is an essential amino acid; however, excessive intake induces oxidative stress associated with memory impairment and reduced hippocampal neurogenesis. Rosmarinic acid (RA), a natural phenolic compound, has been reported to exhibit antioxidant and neuroprotective properties. This study aimed to investigate the effects of RA on L‐met‐induced memory deficits and alterations in hippocampal neurogenesis in adult rats. Fifty‐four male Sprague–Dawley rats were divided into 6 groups: control, L‐met (1.7 g/kg/day), RA10 (10 mg/kg/day), RA30 (30 mg/kg/day), L‐met + RA10 (L‐met: 1.7 g/kg/day and RA: 10 mg/kg/day), and L‐met + RA30 (L‐met: 1.7 g/kg/day and RA: 30 mg/kg/day). Memory performance was evaluated using the novel object location (NOL) and novel object recognition (NOR) tests. Hippocampal neurogenesis was assessed using Ki‐67 and Ki‐67/rat endothelial cell antigen‐1 (RECA‐1) as markers of cell proliferation and vascular‐associated proliferating cells, 5‐bromo‐2′‐deoxyuridine/neuronal nuclear protein (BrdU/NeuN) as a marker of neuronal survival associated with mature neurons and p21 as a marker of cell cycle arrest. The results revealed that L‐met administration significantly impaired memory performance, reduced Ki‐67‐, Ki‐67/RECA‐1‐, and BrdU/NeuN‐positive cells, and increased p21‐positive cells. However, co‐administration of RA (10 and 30 mg/kg) significantly attenuated L‐met‐induced memory deficits and hippocampal neurogenesis‐related impairments. These findings suggest that RA attenuates L‐met‐induced memory impairment and disruption of hippocampal neurogenesis in adult rats.