Renal effects of chronic D-serine administration in a Parkinson’s disease rat model: evidence for a threshold nephrotoxic dose

Abstract D-serine, an endogenous co-agonist at the glycine binding site of NMDA receptor GluN1 subunits, is increasingly studied in Parkinson’s disease, where altered levels have been detected in both patients and animal models. Using a rat model based on α-synuclein overexpression, we evaluated renal effects after eight weeks of daily D-serine administration, alone or in combination with L-DOPA. Given the known acute nephrotoxicity of D-serine in rats, this study addresses the lack of data on chronic exposure. Our results show that a dose of 200 mg/kg induces biological alterations - reflected in growth patterns and water consumption - and peritubular inflammatory infiltrates comparable to the nephrotoxic effect reported after acute treatment. These findings suggest that 200 mg/kg could represent a threshold dose for chronic D-serine administration in rats, providing a useful reference for future studies involving prolonged treatment.