Linezolid alleviates d-galactose-induced anxiogenic or depressive behaviors and memory impairment

. Thirty-six animals were separated into 6 sets (n = 6): [Veh + Veh], [Veh + Lnz] (10 mg/kg), [Veh + Lnz] (20 mg/kg), [Veh + D-gal] (100 mg/kg), [D-gal + Lnz] (10 mg/kg), and [D-gal + Lnz] (20 mg/kg). Both D-gal and Lnz were administered intraperitoneally (i.p) for 2 weeks. After treatment, behavioral tests, i.e., light-dark activity (LDA), tail suspension test (TST), and Morris Water Maze (MWM) were performed on days 14, 15, and 16-18, respectively, to assess anxiety, depression, and memory function. The rodents were decapitated on day 19, and their brains (particularly hippocampus and other brain regions) were isolated, stored at - 40 °C, and then assessed through biochemical and neurochemical estimation. The findings demonstrated that Lnz treatment increased [p < 0.05] the time spent in the light box of LDA and lowered [p < 0.05] immobility time in TST, suggesting anxiolytic- and antidepressant-like effects both alone and in D-gal-treated animals. In the MWM, there was no significant main effect of D-gal on escape latency, but a significant effect of Lnz [p < 0.05] and a significant D-gal × Lnz interaction [p < 0.05] across acquisition, STM and LTM phases. Post hoc comparisons further revealed that Lnz reduced escape latency in both vehicle- and D-gal-treated animals. The reductions were more pronounced in D-gal-exposed groups suggesting a possible modulatory role of Lnz on the performance associated with memory under the conditions of D-gal exposure. Lnz also elevated [p < 0.05] antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and decreased [p < 0.05] the contents of oxidative stress marker (MDA), and inflammatory mediators [interleukin-6 (IL-6), and tumor necrosis factor (TNF-α)] in the hippocampus and rest of the brain following D-gal administration. Moreover, Lnz lowered [p < 0.05] acetylcholinesterase (AChE) activity and raised [p < 0.05] 5-hydroxytryptamine (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) contents in the hippocampus and the rest of the brain after D-gal administration. In molecular docking, Lnz exhibits potential binding affinities of - 8 kcal/mol and - 10 kcal/mol with monoamine oxidase enzymes (MAO-A and MAO-B), docking results provided preliminary evidence of potential binding interactions between Lnz and MAO enzymes, but did not show functional MAO inhibition. Taken together, these findings suggest that Lnz might possess antioxidant and neuroprotective-like effects besides its antibiotic properties, which could modulate D-gal-induced behavioral changes, including anxiety- and depression-like responses and a potential tendency to improve memory-like performance. These observations are exploratory and deserve further investigation.