Chronic Gallic Acid Treatment Attenuates Hippocampal Neurodegeneration in Aged Rats

In recent years, global life expectancy has risen significantly, leading to a marked increase in the elderly population. Aging disproportionately affects the brain, resulting in cognitive decline and increased susceptibility to neurodegenerative diseases. This vulnerability is largely due to the high metabolic activity of neural tissue and its sensitivity to reactive oxygen species (ROS). Consequently, oxidative and inflammatory processes are key contributors to cellular damage and age-related cognitive deficits. These oxidative processes may act as primary drivers of neuronal damage during aging. Recent evidence suggests that phenolic compounds may play a crucial role in neuroprotective strategies. Among these, gallic acid (GA) has garnered attention due to its potent antioxidant and anti-inflammatory properties, which enhance neuronal resilience in animal models. However, the effects of GA on hippocampal neurodegeneration during aging remain unclear. In this study, we evaluated the impact of GA on learning, memory, redox balance, neuroinflammation, apoptosis, and synaptic plasticity in the hippocampus (Hp) of aged rats. Male rats aged 18 months received a daily dose of GA (20 mg/kg) for 60 days. GA treatment significantly improved short- and long-term recognition memory. In the Hp, ROS, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and lipid peroxidation were reduced, while superoxide dismutase (SOD) and catalase (CAT) activities increased. GA administration also decreased caspase-3 expression. Collectively, these findings indicate that GA enhances antioxidant and anti-inflammatory defenses, thereby mitigating hippocampal damage and supporting its potential as a promising therapeutic strategy to prevent or reduce neurodegenerative disorders associated with aging.