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SCIENTIFIC LITERATURE · PPR

Renal Effects of Chronic D-Serine Administration in a Parkinson’s Disease Rat Model: Evidence for a Threshold Nephrotoxic Dose

· 2026-05-12

DOI: 10.21203/rs.3.rs-9551872/v1

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Research overview

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Abstract D-serine, an endogenous co-agonist at the glycine binding site of NMDA receptor NR1 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.

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