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Int. J. Mol. Sci. 2019, 20(2), 250; https://doi.org/10.3390/ijms20020250

Dysregulation of Dopaminergic Regulatory Factors TH, Nurr1, and Pitx3 in the Ventral Tegmental Area Associated with Neuronal Injury Induced by Chronic Morphine Dependence

Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China
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Received: 1 December 2018 / Revised: 6 January 2019 / Accepted: 7 January 2019 / Published: 10 January 2019
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Neurotoxicity)
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Abstract

The ventral tegmental area (VTA), a critical portion of the mesencephalic dopamine system, is thought to be involved in the development and maintenance of addiction. It has been proposed that the dopaminergic regulatory factors TH, Nurr1, and Pitx3 are crucial for determining the survival and maintenance of dopaminergic neurons. Thus, the present study investigated whether abnormalities in these dopaminergic regulatory factors in the VTA were associated with neuronal injury induced by chronic morphine dependence. Rat models with different durations of morphine dependence were established. Thionine staining was used to observe morphological changes in the VTA neurons. Immunohistochemistry and western blot were used to observe changes in the expression of the dopaminergic regulatory proteins TH, Nurr1, and Pitx3. Thionine staining revealed that prolonged morphine dependence resulted in dopaminergic neurons with edema, a lack of Nissl bodies, and pyknosis. Immunohistochemistry showed that the number of TH+, Nurr1+, and Pitx3+ cells, and the number of TH+ cells expressing Nurr1 or Pitx3, significantly decreased in the VTA after a long period of morphine dependence. Western blot results were consistent with the immunohistochemistry findings. Chronic morphine exposure resulted in abnormalities in dopaminergic regulatory factors and pathological changes in dopaminergic neurons in the VTA. These results suggest that dysregulation of dopaminergic regulatory factors in the VTA are associated with neuronal injury induced by chronic morphine dependence. View Full-Text
Keywords: chronic morphine dependence; ventral tegmental area; dopaminergic neurons; TH; Nurr1; Pitx3 chronic morphine dependence; ventral tegmental area; dopaminergic neurons; TH; Nurr1; Pitx3
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Shi, W.; Zhang, Y.; Zhao, G.; Wang, S.; Zhang, G.; Ma, C.; Li, Y.; Cong, B. Dysregulation of Dopaminergic Regulatory Factors TH, Nurr1, and Pitx3 in the Ventral Tegmental Area Associated with Neuronal Injury Induced by Chronic Morphine Dependence. Int. J. Mol. Sci. 2019, 20, 250.

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