Neuroprotective effects of glycine against cisplatin-induced cognitive decline in mice

Background: Cisplatin is a common chemotherapeutic agent known to cause impairments often referred to as “chemo-brain.” Preclinical evidence suggests cisplatin induces toxicity via oxidative stress and neuroinflammation. Methods: Twenty-five healthy adult male BALB/c mice ( n =5 per group) were randomly assigned to five treatment cohorts over a 28-day period. Cisplatin (3 mg/kg) was administered intraperitoneally every fourth day, and glycine (1 g/kg/day) was administered subcutaneously daily. Groups assessed concurrent protection and delayed/reversal intervention. Spatial working memory (Y-maze/spontaneous alternation percentage) and spatial learning [Morris water maze (MWM)/latency to platform] were evaluated before and after treatment using paired T-tests and one-way analysis of variance (ANOVA). Results: Cisplatin administration alone resulted in significant cognitive decline in the Y-naze ( P <0.001) and MWM ( P <0.001). Concurrent administration of glycine (Group 2) provided the greatest protection, resulting in no significant decline in the Y-maze ( P = 0.481) or MWM ( P = 0.986). ANOVA confirmed highly significant overall differences in performance across groups for both the Y-Maze ( P <0.001, F (4,20) = 108.995) and MWM ( F = 52.878, P <0.0001). Delayed glycine also showed mitigation, with Group 5 performing significantly better than Group 3 in the MWM ( P = 0.003). Conclusion: Glycine co-administration largely prevents spatial learning and working memory deficits caused by cisplatin in mice. These findings support the view that cisplatin impairs cognition through inflammatory and oxidative pathways, and suggest that targeting these pathways with simple interventions can be effective. Glycine, an inexpensive and safe naturally occurring molecule, holds promise for mitigating chemotherapy-related cognitive decline during cancer treatment.