Activation of dopaminergic VTA inputs to the mPFC ameliorates chronic stress‐induced breast tumor progression
| Autor: | Jie Tu, Hong Yuchuan, Xu Xirong, Qian Xiao, Yue Liu, Yunhui Liu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Mice chemistry.chemical_compound 0302 clinical medicine Corticosterone Pharmacology (medical) Chronic stress Mice Inbred BALB C Dopaminergic Psychiatry and Mental health unpredictable mild stress neuromodulation Disease Progression MCF-7 Cells Original Article Female neurotransmitter medicine.drug emotion Mice Nude Prefrontal Cortex Breast Neoplasms optogenetic 03 medical and health sciences Breast cancer Dopamine Physiology (medical) medicine cancer Animals Humans Pharmacology Tyrosine hydroxylase business.industry Dopaminergic Neurons Ventral Tegmental Area Cancer Original Articles medicine.disease Xenograft Model Antitumor Assays Mice Inbred C57BL Optogenetics 030104 developmental biology chemistry Tumor progression Chronic Disease Cancer research business Stress Psychological 030217 neurology & neurosurgery |
| Zdroj: | CNS Neuroscience & Therapeutics |
| ISSN: | 1755-5949 1755-5930 |
| DOI: | 10.1111/cns.13465 |
| Popis: | Aims Chronic stress plays an important role in promoting the progression and migration of cancers. However, little is known of any direct impact on tumor progression related to the regulation of emotion‐related circuitry. The aim of this study was to explore the neural‐circuit mechanisms underlying stress‐induced progression of cancers and the impact of emotion‐related regulation of circuitry on tumor growth. Methods Optogenetic manipulation was applied to unpredictable chronic mild stress (UCMS)–treated mice bearing breast tumor cell. The stress‐related hormones, tumor‐related cytokines, the tyrosine hydroxylase (TH)–positive neurons and their fibers, dopamine receptor–positive cells, and anxiety level were measured using ELISA, immunohistochemical staining, fluorescence in situ hybridization, and behavioral test, respectively. Results By investigating breast cancer mouse models with a chronic mild stress model, optogenetic stimulation, and behavioral analysis, we show that chronic stress induced anxiety‐like behavior in mice and increased serum concentration of norepinephrine and corticosterone, hormones closely related to stress and anxiety. Optogenetic activation of VTA TH terminals in the mPFC rescued anxiety‐like behavior induced by chronic stress. Chronic stress resulted in marked progression of breast tumors, and repetitive optogenetic activation of VTA TH terminals in the mPFC significantly attenuated stress‐induced progression of breast cancers and reduced serum concentration of norepinephrine and corticosterone. Furthermore, there was a positive correlation between serum norepinephrine or corticosterone concentration and tumor size. Conclusions These findings indicate a positive role of an emotion regulation circuit on the progression of breast cancer and reveal a link between stress, emotion regulation, and the progression of breast cancers. Our findings provide new insights pertinent to therapeutic interventions in the treatment of breast cancers. Chronic stressors resulted in marked progression of breast tumors. Repetitive activation of the VTATH terminals within the mPFC by optogenetic manipulation significantly attenuated stress‐induced progression of breast tumors |
| Databáze: | OpenAIRE |
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