Published in

Oxford University Press, Journal of Pharmacy and Pharmacology, 8(70), p. 1059-1068, 2018

DOI: 10.1111/jphp.12936

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Ineffectiveness of saxagliptin as a neuroprotective drug in 6-OHDA-lesioned rats

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Abstract Objectives To determine whether the drug saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor which is utilized for the treatment of Diabetes Mellitus, has neuroprotective effects in the animal model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) in rats. Methods Male Wistar rats (weighing 280–300 g) received a bilateral infusion of 6-OHDA in the substantia nigra. Twenty-four hours later, they were treated with saxagliptin (1 mg/kg, p.o) once daily, for 21 days. The motor function was evaluated using the open field and rotarod (RT) tests. In addition, cognition was assessed with the novel object recognition test (ORT). After the evaluation of the behavioural tests, the animals were transcardially perfused to perform immunohistochemistry staining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc). Key findings Saxagliptin impaired the memory of animals in the sham group. Conclusions Saxagliptin treatment did not exhibit neuroprotection and it did not improve the cognitive and motor deficits in the 6-OHDA model of PD. Interestingly, when saxagliptin was administered to the sham animals, a cognitive decline was observed. Therefore, this drug should be investigated as a possible treatment for PTSD.