Sitagliptin rescues memory deficits in Parkinsonian rats via upregulating BDNF to prevent neuron and dendritic spine loss

ABSTRACT

Objectives: Parkinson’s disease (PD) is a neurodegenerative disease with high morbidity among adults worldwide that causes tremendous trouble to people’s lives. The purpose of this study was to investigate the impact of sitagliptin on PD and its potential mechanism.

Methods: First, the memory of rats in each group was evaluated with the Morris water maze (MWM) test and the passive avoidance test. Then, both brain-derived neurotrophic factor (BDNF) protein and mRNA levels were detected by ELISA and qPCR assays, respectively. Then, rapid Golgi impregnation was used to observe the density of dendritic spines in the hippocampal CA1 area. Finally, k252a, an antagonist of Trk receptors, was used to block the binding of BDNF with its receptors, and the effects of sitagliptin on PD improvement were detected.

Results: Our study showed that sitagliptin improved memory deficits in PD rats. Meanwhile, the expression level of BDNF and tyrosine hydroxylase (TH) was upregulated, and the density of dendritic spine was increased by sitagliptin administration. Moreover, K252a administration blocked the positive effects of sitagliptin on memory in PD rats.

Discussion: Sitagliptin rescued the memory deficits, which was achieved by upregulating BDNF to prevent neuronal death and dendritic spine loss. Our findings indicate that sitagliptin might be a promising potential drug for PD treatment in the future.

KEYWORDS:

• Parkinson’s disease
• Sitagliptin
• BDNF
• dendritic spine
• Morris Water Maze
• passive avoidance

Acknowledgments

This study was supported by the Second Affiliated Hospital of Harbin Medical University. All authors have read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was funded by Innovative talent fund of Harbin Science and Technology Bureau (no. 2016RAQXJ201) and Postdoctoral fund in Heilongjiang province (no. LBH-Z15150). This study was supported by the Second Affiliated Hospital of Harbin Medical University.

Notes on contributors

Lan Ma

Doctor Ma Lan, Professor, chief physician. She is director of geriatric department of No.2 Affiliated Hospital of Harbin Medical University. She is engaged in the prevention, diagnosis, treatment and scientific research of geriatric diseases, and is able to master the diagnosis and treatment of common diseases and difficult diseases of the elderly.