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Dysregulation of Dopaminergic Regulatory Factors TH, Nurr1, and Pitx3 in the Ventral Tegmental Area Associated with Neuronal Injury Induced by Chronic Morphine Dependence
- Source :
- International Journal of Molecular Sciences, Volume 20, Issue 2, International Journal of Molecular Sciences, Vol 20, Iss 2, p 250 (2019)
- Publication Year :
- 2019
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2019.
-
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.
- Subjects :
- Male
0301 basic medicine
Gene Expression
lcsh:Chemistry
0302 clinical medicine
Nuclear Receptor Subfamily 4, Group A, Member 2
lcsh:QH301-705.5
Spectroscopy
media_common
chronic morphine dependence
medicine.diagnostic_test
Dopaminergic
General Medicine
Immunohistochemistry
Computer Science Applications
Ventral tegmental area
Nurr1
medicine.anatomical_structure
Nissl body
symbols
TH
Morphine Dependence
medicine.drug
medicine.medical_specialty
Tyrosine 3-Monooxygenase
media_common.quotation_subject
ventral tegmental area
Pitx3
Biology
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
symbols.namesake
Western blot
Dopamine
Internal medicine
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
Homeodomain Proteins
dopaminergic neurons
Addiction
Organic Chemistry
Rats
030104 developmental biology
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
nervous system
030217 neurology & neurosurgery
Pyknosis
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....a2d43a501cf62569a9c28555ce26505b
- Full Text :
- https://doi.org/10.3390/ijms20020250