Steroidal anti inflammatory drug betamethasone significantly alters level of striatal dopamine in a rat model of Parkinson’s disease

Mehdi Shafiee Ardestani,Amin Geravand,Mostafa Saffari,Nasir Mohajer,Hasan Mehrab

doi:10.1038/npre.2008.2330.1

Abstract

AbstractMany scientific efforts have been well done to investigate the effects of anti inflammatory agents on the degenerative brain diseases such as Parkinson’s (PD) or Alzheimer’s disease and their affiliated sings. Previously we showed the effectiveness of steroids on rigidity of PD and in the study for further mechanistic investigation of that observation the microdialysis technique was employed to determine the striatal dopamine changes in parkinsonian rats after administration of betamethasone (0.12, 0.24 mg/kg) respectively. Our findings showed us the significant increase in the striatal dopaminergic neurotransmission (P<0.05) after administration of betamethasone comparing to the controls. These observations suggest a new mechanism for betamethasone on striatum dopaminergic neurotransmission leading us to gather further evidence about effectiveness of betamethasone in PD.

Highlights

Parkinson’s disease (PD) is a degenerative neurodopaminergic disease in the nigrostriatal pathway of humans/ animals, and the resultant losses of nerve terminals accompanied by dopamine deficiency in this pathway are responsible for most of the movement disorders. [1, 2] Increasing evidence suggests that an inflammatory reaction and pathological processes seen in many neurodegenerative disorders, including PD
The results showed the significant increase in amount of dopamine P
The study indicated the possibility of betamethasone to increase the release of dopamine in the striatal pathway, subsequently motivating the use of this agent to address improvements in brain degeneration such as PD, movement disorders effects as investigated previously [4, 8] The present study did not directly study improvements in movement disorders or the production of neuroprotective effects; at the same time, the present results hint at one possible mechanisms via which these effects can occur when steroidal anti inflammatory agents are used: increasing levels of striatal dopamine

Summary

Introduction

Parkinson’s disease (PD) is a degenerative neurodopaminergic disease in the nigrostriatal pathway of humans/ animals, and the resultant losses of nerve terminals accompanied by dopamine deficiency in this pathway are responsible for most of the movement disorders. [1, 2] Increasing evidence suggests that an inflammatory reaction and pathological processes seen in many neurodegenerative disorders, including PD. [2] In cell culture and animal models, inflammation contributes to the neuronal damage and anti inflammatory agents such as dexamethasone has been shown to provide some neuroprotection or treatment of PD affiliated disorders such as rigidity by aspirin and betamethasone in animal model of PD. [3] In agreement the significant changes in the striatal neurotransmissions after the Cyclooxygenase-2 (COX2) as an important component of the inflammation[4] but not COX-1 selective inhibition were observed. [3] In agreement the significant changes in the striatal neurotransmissions after the Cyclooxygenase-2 (COX2) as an important component of the inflammation[4] but not COX-1 selective inhibition were observed. These researches showed the significant increase in dopaminergic or decrease in gamma amino butyric acid (GABA)ergic-glutamatergic neurotransmissions after only selective COX-2 inhibition, coincidently the PD affiliated disorders significantly improved. The present work studies, assay of neurotransmitter dopamine concentration in the striatum of parkinsonian rats following administration of steroidal anti inflammatory drug betamethasone The study of striatal dopaminergic interactions has special importance due to the physiological and pathophysiological processes of these systems, such as Parkinson's or Alzheimer’s disease. [1, 2]

Methods

Results

Conclusion