ASSESSING THE NEUROTOXIC EFFECTS OF FOSFOMYCIN ON COGNITION AND HIPPOCAMPAL NEUROGENESIS IN ADULT FEMALE RATS

Neurogenesis, the generation of new functional neurons from neural stem cells (NSCs), occurs in several brain regions including the hippocampal dentate gyrus and is influenced by environmental and pharmacological factors such as antibiotics. Fosfomycin, a broad-spectrum antibiotic commonly prescribed for urinary tract infections (UTIs), has previously shown neurotoxic effects in male rats. Given the higher prevalence of UTIs in females, this study investigated Fosfomycin’s neurotoxicity on motor performance, pain sensitivity, cognitive function, and hippocampal neurogenesis in adult female Sprague Dawley rats.
Animals were divided into four groups: naïve, sham (saline), low-dose Fosfomycin (177 mg/kg), and high-dose Fosfomycin (354 mg/kg), administered intraperitoneally twice daily for seven days. Behavioral tests included the Y-Maze and novel object recognition (NOR) for memory, the Rotarod test for motricity, and thermal sensitivity assessment for hyperalgesia, alongside estrous cycle tracking. Bromodeoxyuridine (BrdU) injections were used to label proliferating NSCs in the hippocampus.
Results showed no significant changes in motricity, thermal sensitivity, or spatial memory. However, Fosfomycin-treated rats displayed reduced entries and travel distance in the NOR test, indicating impaired recognition memory and exploratory behavior. A high Fosfomycin dose significantly decreased proliferating NSCs in the hippocampal dentate gyrus, while low-dose treatment upregulated FGF2, NGF, and TrkB mRNA levels, suggesting compensatory neurotrophic responses.
These findings reveal Fosfomycin-induced neurotoxicity and cognitive deficits in female rats, emphasizing potential risks of its clinical use and underscoring the need for further studies on safer antibiotic applications affecting the nervous system.