Inhibition of p38 pathway-dependent MPTP-induced dopaminergic neurodegeneration in estrogen receptor alpha knockout mice
| Autor: | Jin Tae Hong, Ki Wan Oh, Seikwan Oh, Chul Ju Hwang, Mi Hee Park, Jae Suk Yun, Dong Young Choi, Young Jung Lee, Sang-Bae Han, Yu Yeon Jung |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Substantia nigra p38 Mitogen-Activated Protein Kinases Mice 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine Endocrinology Dopamine Internal medicine medicine Animals Neuroinflammation Mice Knockout Tyrosine hydroxylase Endocrine and Autonomic Systems Dopaminergic Neurons MPTP Dopaminergic Estrogen Receptor alpha Estrogens Parkinson Disease Corpus Striatum Enzyme Activation Mice Inbred C57BL Substantia Nigra Disease Models Animal 030104 developmental biology nervous system chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Nerve Degeneration Monoamine oxidase B Estrogen receptor alpha 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Hormones and Behavior. 80:19-29 |
| ISSN: | 0018-506X |
| DOI: | 10.1016/j.yhbeh.2016.01.011 |
| Popis: | Approximately, 7-10 million people in the world suffer from Parkinson's disease (PD). Recently, increasing evidence has suggested the protective effect of estrogens against nigrostriatal dopaminergic damage in PD. In this study, we investigated whether estrogen affects 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral impairment in estrogen receptor alpha (ERα)-deficient mice. MPTP (15mg/kg, four times with 1.5-h interval)-induced dopaminergic neurodegeneration was evaluated in ERα wild-type (WT) and knockout (KO) mice. Larger dopamine depletion, behavioral impairments (Rotarod test, Pole test, and Gait test), activation of microglia and astrocytes, and neuroinflammation after MPTP injection were observed in ERα KO mice compared to those in WT mice. Immunostaining for tyrosine hydroxylase (TH) after MPTP injection showed fewer TH-positive neurons in ERα KO mice than WT mice. Levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC, metabolite of dopamine) were also lowered in ERα KO mice after MPTP injection. Interestingly, a higher immunoreactivity for monoamine oxidase (MAO) B was found in the substantia nigra and striatum of ERα KO mice after MPTP injection. We also found an increased activation of p38 kinase (which positively regulates MAO B expression) in ERα KO mice. In vitro estrogen treatment inhibited neuroinflammation in 1-methyl-4-phenyl pyridium (MPP+)-treated cultured astrocyte cells; however, these inhibitory effects were removed by p38 inhibitor. These results indicate that ERα might be important for dopaminergic neuronal survival through inhibition of p38 pathway. |
| Databáze: | OpenAIRE |
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