Minocycline Alleviates Cluster Formation of Activated Microglia and Age-dependent Dopaminergic Cell Death in the Substantia Nigra of Zitter Mutant Rat
| Autor: | Ayuka Ehara, Shuichi Ueda, Daisuke Taguchi, Taro Kadowaki, Koichi Hirata, Shin Ichi Sakakibara, Kazuhiko Nakadate |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Programmed cell death
Histology Physiology dopamine neuron Substantia nigra pro-inflammatory cytokines Biochemistry Pathology and Forensic Medicine Midbrain 03 medical and health sciences minocycline Dopaminergic Cell medicine 030304 developmental biology activated microglia 0303 health sciences Microglia Chemistry Pars compacta 030302 biochemistry & molecular biology Dopaminergic Regular Article Cell Biology Molecular biology medicine.anatomical_structure substantia nigra nervous system Tumor necrosis factor alpha |
| Zdroj: | Acta Histochemica et Cytochemica |
| ISSN: | 1347-5800 0044-5991 |
| DOI: | 10.1267/ahc.20-00022 |
| Popis: | Microglial activation is a component of neurodegenerative pathology. Here, we examine whether activated microglia participate in age-related dopaminergic (DA) cell death in the substantia nigra pars compacta (SNc) of the zitter (zi/zi) rat, a mutant characterized by deletion of the attractin gene. Confocal microscopy with double-immunohistochemical staining revealed activated microglia-formed cell-clusters surrounding DA neurons in the SNc from 2 weeks after birth. An immunoelectron microscopic study showed that the cytoplasm of activated microglia usually contains phagosome-like vacuoles and lamellar inclusions. Expression levels of the pro-inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) were increased in the midbrain of 2-month-old zi/zi rats. Chronic treatment with the anti-inflammatory agent minocycline altered the morphology of the microglia, reduced cluster formation by the microglia, and attenuated DA cell death in the SNc, and reduced the expression of IL-1β in the midbrain. These results indicate that activated microglia, at least in part and especially at the initial phase, contribute to DA cell death in the SNc of the zi/zi rat. |
| Databáze: | OpenAIRE |
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