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Subject Area

Medical Pharmacology

Article Type

Original Study

Abstract

Background: Parkinson's disease (PD) is a widespread neurodegenerative illness causing cognitive impairment and dementia with limited prevention options.

Objectives: To investigate the neuroprotective effects of sitagliptin (SITA), and pioglitazone (PIO) on cognitive functions in rotenone (ROT)-induced PD in rats.

Methods: Sprague-Dawley rats (n=50) were randomly categorized into five groups; control group, ROT group (3 mg/kg/d), ROT+SITA group (30 mg/kg/d), ROT+PIO group (30 mg/kg/d), and ROT+SITA+ PIO (30 mg/kg/d). Cognition was evaluated using a modified elevated plus maze (EPMT), and novel object recognition (NORT) test. Biochemically, striatal dopamine level, hippocampal brain-derived neurotrophic factor (BDNF), malondialdehyde (MDA), and reduced glutathione (GSH) were measured. Histopathological changes in hippocampal and cerebral tissues were evaluated.

Results: ROT significantly diminished cognitive performance in rats revealed by a significant increase in the final retention transfer latency (FRTL) in EPMT (P = 0.001), and a significant reduction of memory index by ~46% (P = 0.001) in NORT compared with the control group. ROT significantly induced the disease biochemically (increased MDA, with a reduction in GSH, BDNF, and dopamine levels), and histopathological (increased hippocampal and cerebral neuronal degeneration, apoptosis, vascular congestion, and decreased immunoreactivity of hippocampal microtubule-associated proteins 1A/1B light chain 3 (LC3), and autophagy-related 7 Antibody (ATG7). However, treatment with SITA, PIO, or their combined administration markedly improved the behavior of the rats, and partially reversed the biochemical alterations that were histopathological validated.

Conclusion: Treatment with SITA, PIO, or their combination could be a promising option for the prevention of cognitive dysfunctions in ROT-induced PD.

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