EFFECTIVENESS OF DIPEPTIDYL PEPTIDASE – 4 INHIBITORS IN STREPTOZOTOCIN INDUCED NEURODEGENERATIVE MICE

Introduction: Neurodegenerative diseases are incurable and debilitating condition that results in progressive degeneration and / or death of nerve cells. Anti-oxidants, Antihyper-glycemics and insulin sensitizing agents are reported for reducing cognitive dysfunction in diabetes. Decreasing GLP-1 degradation using Dipeptidyl Peptidase-4 (DPP-4) inhibitors has been shown to be effective for treating type-2 diabetes and neurodegeneration. Objective: In present study neuroprotective effect of sitagliptin and saxagliptin on streptozotocin induced neurodegenerative mice had been evaluated. Materials and Methods: Neurodegeneration was induced by single dose of Streptozotocin (120mg/kg I.P) and started drug treatment (Sitagliptin and Saxagliptin) after 28 days of Streptozotocin single dose treatment for next 21 days. Streptozotocin induced memory decline was confirmed by behavioural study and Inflexion Ratio – IR. Results: Memory decline was overturned by Saxagliptin (0.5 and 1mg/kg p.o) and Sitagliptin (10 and 20mg/kg p.o). In addition to above, Saxagliptin (1mg/kg p.o) and Sitagliptin (20mg/kg p.o) had reversed levels of dopamine, nor-adrenaline and serotonin in brain as compared to only Streptozotocin treated animals, suggesting neuroprotective activity of chosen two DPP-4 inhibitors (saxagliptin and sitagliptin). Conclusion: These results demonstrate that DPP-4 inhibitors drugs that are effective in treatment of type-2 diabetes have neuroprotective properties also. Further research is required to clarify the molecular mechanism involved in neuroprotection.