Dexmedetomidine, an alpha-2 adrenoceptors agonist, provides a neuroprotective effect for dopaminergic neurons in the substantia nigra and attenuates glucose imbalance in the 6-hydroxydopamine animal model of Parkinson’s disease

ABSTRACT

Introduction

Studies have shown that dexmedetomidine (DEX, an a2-adrenoceptors agonist) provides a neuroprotective effect and influences blood glucose levels. Here, we evaluated the effect of prolonged treatment with low doses of DEX on the survival rate of dopaminergic (DAergic) neurons in the substantia nigra and also serum glucose levels in 6-hydroxydopamine (6-OHDA) – induced Parkinson’s disease (PD) in the rat.

Material and Methods

The neurotoxin of 6-OHDA was injected into the medial forebrain bundle by stereotaxic surgery. DEX (25 and 50 µg/kg, i.p) and yohimbine, an a2-adrenoceptor antagonist (1 mg/kg, i.p) were administered before the surgery to the 13 weeks afterward. Apomorphine-induced rotational tests and blood sampling were carried out before the surgery and multiple weeks after that. Thirteen weeks after the surgery, the rats’ brain was transcardially perfused to assess the survival rate of DAergic neurons using the tyrosine hydroxylase (TH) immunohistochemistry.

Results

DEX remarkably attenuated the severity of rotational behavior and reversed the progress of the PD. It also increased the number of TH-labeled neurons by up to 60%. The serum glucose levels in 6-OHDA-received rats did not change in the third and seventh weeks after the surgery but decreased significantly in the thirteenth week. Treatment with DEX prevented this decrement in glucose levels. On the other hand, Treatment with yohimbine did not affect PD symptoms and glucose levels.

Conclusion

Our data indicate that DEX through neuroprotective activity attenuates the severity of 6-OHDA-induced PD in rats. DEX might also prevent hypoglycemia during the progress of the PD.

KEYWORDS:

• Parkinson’s disease
• 6-hydroxydopamine
• dexmedetomidine
• yohimbine
• serum glucose levels
• substantia nigra
• rat

Acknowledgments

The authors thank the staff of Bouali Hospital in Qazvin for her assistance in assessments of glucose and insulin levels.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used during the current study are available from the corresponding author upon reasonable request.

Authors’ contribution

Haghdoost-Yazdi H. designed the study, and Darabi, S. Zaferani Y did stereotaxic surgery and behavioral tests. Farzam S.A. did laboratory measurements and immunohistochemistry assessments. Data were analyzed by Haghdoost-Yazdi H, and all authors wrote the manuscript.

Ethics approval

All procedures of the present study were carried out according to the guidelines of animal experiments of the Research Council at Qazvin University of Medical Sciences.

Additional information

Funding

This work was supported by a grant-in-aid from Qazvin University of Medical Sciences [grant number: IR.QUMS.AEC.1401.003].