Sex-dependent effects of zoledronic acid on learning, memory, and hippocampal cytokines in a d-galactose-induced aging model.

OBJECTIVE

The relationship between age-related cognitive impairment and neuroinflammation has received increasing attention in experimental neuroscience. This study investigated the effects of zoledronic acid on learning, memory, and hippocampal cytokine levels in female and male rats in a d-galactose-induced aging model.

METHODS

Adult female and male Wistar rats (250-300 g) were used. An aging-like condition was induced by chronic d-galactose administration (120 mg/kg for 10 weeks). The effects of zoledronic acid (0.4 mg/kg) were evaluated using behavioral tests of learning and memory and biochemical analyses in both sexes.

RESULTS

d-galactose impaired cognitive performance, and this impairment was more pronounced in female rats. Zoledronic acid attenuated cognitive impairment more clearly in females, whereas its effects were more limited in males. Hippocampal tissue analyses showed that the elevated proinflammatory cytokine levels induced by d-galactose were reduced by zoledronic acid treatment in both sexes, supporting a possible protective and anti-inflammatory profile in this model.

CONCLUSIONS

These findings suggest that zoledronic acid may exert protective effects on cognitive function and neuroinflammatory processes in a d-galactose-induced aging model. The results also indicate that these effects may be more pronounced at the behavioral level in females. Further studies are needed to clarify the effects of zoledronic acid on age-related cognitive impairment and neuroinflammation and to better understand their sex-dependent nature.