Evaluation of the Association Between Serum Levels of Testosterone and Prolactin With 6- Hydroxydopamine- Induced Parkinsonism in Male Rats

Razaghi, Roghaieh; Piri, Hossein; Jafari, Hanieh; Rastgoo, Nafiseh; Hosseini, Mohammad Ali; Haghdoost – Yazdi, Hashem

doi:10.32598/bcn.2021.671.3

Volume 12, Issue 4 (July & August 2021) BCN 2021, 12(4): 453-464 | Back to browse issues page

‎ 10.32598/bcn.2021.671.3

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Razaghi R, Piri H, Jafari H, Rastgoo N, Hosseini M A, Haghdoost – Yazdi H. Evaluation of the Association Between Serum Levels of Testosterone and Prolactin With 6- Hydroxydopamine- Induced Parkinsonism in Male Rats. BCN 2021; 12 (4) :453-464
URL: http://bcn.iums.ac.ir/article-1-1556-en.html

Evaluation of the Association Between Serum Levels of Testosterone and Prolactin With 6- Hydroxydopamine- Induced Parkinsonism in Male Rats

Roghaieh Razaghi¹

, Hossein Piri²

, Hanieh Jafari¹

, Nafiseh Rastgoo³

, Mohammad Ali Hosseini³

, Hashem Haghdoost – Yazdi ^*

1- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
2- Cellular and Molecular Research Center, Research Institute for Prevention of Non- Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran.
3- Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran.

Abstract:

Introduction: Parkinson’s Disease (PD) associates with changes in sex hormones; however, it remains unknown whether this is either a cause for or a result of the disease. To further evaluate it, we investigated if the development of 6-Hydroxydopamine (6-OHDA)-induced Parkinsonism changes the serum levels of testosterone and prolactin or not.
Methods: 6-OHDA was injected into the medial forebrain bundle using stereotaxic surgery. The development of Parkinsonism was evaluated by apomorphine-induced rotational test and the immunofluorescence labeling of Dopaminergic (DA) neurons in substantia nigra. The necessary blood samples were collected before the toxin and in the third and sixth weeks afterward. The hormones levels were determined using Enzyme-Linked Immunosorbent Assay (ELISA) kits.
Results: The severity of rotations was different among 6-OHDA-treated rats; accordingly, they were divided into two subgroups of severe and mild parkinsonian rats. The degeneration of DA neurons was observed in both subgroups; however, it was significantly less in the mild group. In the sixth week after the toxin, testosterone level increased but only in the severe subgroup. Prolactin increased in both subgroups in the third week after the toxin but returned to normal in the sixth week. There was no association between the pre-toxin levels of these hormones and the intensity of Parkinsonism.
Conclusion: Our findings indicated that the development of 6-OHDA-induced Parkinsonism increases the serum levels of testosterone and prolactin. Increased prolactin occurred earlier and was observed in rats with less DA neuronal loss. Therefore, prolactin levels can predict the death of DA neurons before the clinical signs of PD were revealed.

Keywords: Parkinson’s disease, 6-hydroxydopamine, Testosterone, Prolactin, Dopaminergic

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● 6-OHDA-induced Parkinsonism is associated with an increase in testosterone and prolactin.
● Testosterone levels increased six weeks after 6-OHDA only in severe parkinsonian rats.
● Prolactin increased in the third week after 6-OHDA but returned to normal in the sixth week.
● Prolactin increased in both mild and severe parkinsonian rats.
● Serum prolactin level can predict PD before its clinical signs are revealed.
Plain Language Summary
Parkinson's Disease (PD) is the most common movement disorder and represents the second most common neurodegenerative disease after Alzheimer's disease. PD affects 1–2 per 1000 of the population at any time. Its prevalence is increasing with age and affects 1% of the people above 60 years. The leading cause of PD is the death of neurons called dopaminergic neurons in the brain stem. Clinical diagnostic of PD relies on motor symptoms of tremor, rigidity, and bradykinesia. However, these signs appear when many dopaminergic neurons are already destroyed, and the disease is in advanced stages. Thus, nonmotor symptoms which frequently precede the onset of motor symptoms, have gained increasing attention. In this regard, biomarkers have more chance. A biomarker is an indicator of a particular disease that can be used to evaluate its progress. Identifying specific biomarkers for neurodegenerative disorders is one of the main goals of the current clinical research. Usually, researchers estimate the change in blood parameters to find a biomarker for a specific disease. In the past decades, researchers have developed PD in rats. Through a certain surgery, a neurotoxin called 6-hydroxydopamine is injected into a particular site in the brain. This toxin gradually destroys dopaminergic neurons in the brain stem and thereby generates PD in rats. Because PD is an age-related disease and blood levels of sex hormones change with age, we assessed changes in blood levels of two sex hormones of testosterone and prolactin in rats with PD. Our findings show that PD development in rats is associated with an increase in serum levels of testosterone and prolactin. An increase in prolactin occurred earlier and was observed in rats with less dopaminergic neuronal loss. Therefore, prolactin level probably can predict PD before its clinical signs have appeared.

Type of Study: Original | Subject: Cellular and molecular Neuroscience
Received: 2019/07/13 | Accepted: 2021/06/30 | Published: 2021/07/1

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