Activation of dopaminergic VTA inputs to the mPFC ameliorates chronic stress-induced breast tumor progression.
Activation of dopaminergic VTA inputs to the mPFC ameliorates chronic stress-induced breast tumor progression.
复制标题
激活 mPFC 的多巴胺能 VTA 输入可改善慢性应激诱导的乳腺肿瘤进展
DOI：
10.1111/cns.13465
复制
发表时间：
2021-03
影响因子：
5.5
通讯作者：
Tu J
中科院分区：
文献类型：
--
作者：
Xu XR;Xiao Q;Hong YC;Liu YH;Liu Y;Tu J
慢性应激在促进癌症的进展和迁移中起着重要作用。然而，很少有人知道与情绪相关回路调节有关的肿瘤进展的任何直接影响。本研究的目的是探索压力诱导癌症进展的神经回路机制以及与情绪相关的回路调节对肿瘤生长的影响。将光遗传学操作应用于不可预测的慢性轻度应激（UCMS）处理的携带乳腺肿瘤细胞的小鼠。分别采用ELISA法、免疫组化染色法、荧光原位杂交法和行为学测试法检测应激相关激素、肿瘤相关细胞因子、酪氨酸羟化酶（TH）阳性神经元及其纤维、多巴胺受体阳性细胞和焦虑水平。通过使用慢性轻度应激模型、光遗传学刺激和行为分析研究乳腺癌小鼠模型，我们发现慢性应激诱导小鼠的焦虑样行为，并增加去甲肾上腺素和皮质酮的血清浓度，这些激素与应激和焦虑密切相关。mPFC中VTA TH终末的光遗传激活挽救了慢性应激诱导的焦虑样行为。慢性应激导致乳腺肿瘤显着进展，mPFC中VTA TH末端的重复光遗传学激活显着减弱了应激诱导的乳腺癌进展，并降低了去甲肾上腺素和皮质酮的血清浓度。此外，血清去甲肾上腺素或皮质酮浓度与肿瘤大小呈正相关。这些发现表明情绪调节回路对乳腺癌的进展具有积极作用，并揭示了压力，情绪调节和乳腺癌进展之间的联系。我们的研究结果为乳腺癌的治疗干预提供了新的见解。慢性应激源导致乳腺肿瘤的显著进展。通过光遗传学操作重复激活mPFC内的VTATH终末可显著减弱乳腺肿瘤的应激诱导进展
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. 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. 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. 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
登录
查看更多内容
影响因子：
--
作者：
Caceres S;Peña L;Silvan G;Illera MJ;Woodward WA;Reuben JM;Illera JC
通讯作者：
Illera JC
影响因子：
50.3
作者：
Dolma S;Selvadurai HJ;Lan X;Lee L;Kushida M;Voisin V;Whetstone H;So M;Aviv T;Park N;Zhu X;Xu C;Head R;Rowland KJ;Bernstein M;Clarke ID;Bader G;Harrington L;Brumell JH;Tyers M;Dirks PB
通讯作者：
Dirks PB
影响因子：
17.7
作者：
Kendler, KS;Karkowski, LM;Prescott, CA
通讯作者：
Prescott, CA
影响因子：
6.2
作者：
Giordano, SH;Cohen, DS;Hortobagyi, GN
通讯作者：
Hortobagyi, GN
影响因子：
64.8
作者：
通讯作者：
--