Behavioral defects and downregulation of hippocampal BDNF and nNOS expression in db/db mice did not improved by chronic TGF-β2 treatment.
Behavioral defects and downregulation of hippocampal BDNF and nNOS expression in db/db mice did not improved by chronic TGF-β2 treatment.
复制标题
DOI：
10.3389/fphys.2022.969480
复制
发表时间：
2022
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
流行病学证据表明，糖尿病与抑郁和焦虑等情绪障碍之间存在联系。尽管外周或中枢炎症可以解释这种联系，但分子机制尚未完全了解，并且很少有针对糖尿病或情绪障碍的有效治疗方法。在本研究中，我们旨在确定转化生长因子（TGF）-β2（一种抗炎物质）是否可能代表糖尿病相关情绪行为的潜在治疗剂。海马中的TGF-β2表达受到抗焦虑药物和压力暴露的影响，它能够穿过血脑屏障，并且作为运动诱导的生理性脂肪因子调节葡萄糖稳态。因此，我们假设长期注射 TGF-β2 可以改善糖尿病相关的葡萄糖耐受不良和情绪失调。为了确定长期施用 TGF-β2 对糖尿病的影响，我们将含有 TGF-β2 的渗透泵植入 2 型糖尿病小鼠（db/db 小鼠）中，并连续 12 天向年龄匹配的非糖尿病对照野生型小鼠和 db/db 小鼠输注载体（PBS）。为了评估焦虑样行为和葡萄糖稳态，对小鼠进行了高架十字迷宫测试和腹膜内葡萄糖耐量测试。 12天后获取海马和性腺周围内脏白色脂肪组织性腺周围白色脂肪组织样本。与我们的假设相反，TGF-β2输注对糖尿病相关的葡萄糖耐受不良或糖尿病相关的行为缺陷（例如不活动）没有影响。在 db/db 小鼠中，pgWAT 中炎症标志物的表达较高，但海马中则不然，前者可通过 TGF-β2 输注得到改善。 db/db 小鼠中脑源性神经营养因子和神经元一氧化氮合酶（焦虑样行为的重要调节因子）的表达较低，但 TGF-β2 输注并不影响其表达。我们的结论是，尽管 TGF-β2 降低了糖尿病小鼠脂肪组织中促炎标志物的表达，但它并不能改善它们的肥胖或情绪失调。
Epidemiological evidence suggests that there is a link between diabetes and mood disorders, such as depression and anxiety. Although peripheral or central inflammation may explain this link, the molecular mechanisms are not fully understood and few effective treatments for diabetes or mood disorders are available. In the present study, we aimed to determine whether transforming growth factor (TGF)-β2, an anti-inflammatory substance, might represent a potential therapeutic agent for diabetes-related mood behaviors. TGF-β2 expression in the hippocampus is affected by anxiolytic drugs and stress exposure, it is able to cross the blood-brain barrier, and it is as an exercise-induced physiological adipokine that regulates glucose homeostasis. Therefore, we hypothesized that a chronic TGF-β2 infusion would ameliorate diabetes-related glucose intolerance and mood dysregulation. To determine the effects of the chronic administration of TGF-β2 on diabetes, we implanted osmotic pumps containing TGF-β2 into type 2 diabetic mice (db/db mice), and age-matched non-diabetic control wild type mice and db/db mice were infused with vehicle (PBS), for 12 consecutive days. To assess anxiety-like behaviors and glucose homeostasis, the mice underwent elevated plus maze testing and intraperitoneal glucose tolerance testing. Hippocampal and perigonadal visceral white adipose tissue perigonadal white adipose tissue samples were obtained 12 days later. Contrary to our hypothesis, TGF-β2 infusion had no effect on diabetes-related glucose intolerance or diabetes-related behavioral defects, such as inactivity. In db/db mice, the expression of inflammatory markers was high in pgWAT, but not in the hippocampus, and the former was ameliorated by TGF-β2 infusion. The expression of brain-derived neurotrophic factor and neuronal nitric oxide synthase, important regulators of anxiety-like behaviors, was low in db/db mice, but TGF-β2 infusion did not affect their expression. We conclude that although TGF-β2 reduces the expression of pro-inflammatory markers in the adipose tissue of diabetic mice, it does not ameliorate their obesity or mood dysregulation.
登录
查看更多内容
影响因子：
3.7
作者：
Grassi, Daniela;Franz, Henriette;Vogel, Tanja
通讯作者：
Vogel, Tanja
影响因子：
7
作者：
Coppack, SW
通讯作者：
Coppack, SW
影响因子：
7.7
作者：
Iglesias, MA;Ye, JM;Kraegen, EW
通讯作者：
Kraegen, EW
影响因子：
15.1
作者：
Fourrier, Celia;Bosch-Bouju, Clementine;Castanon, Nathalie
通讯作者：
Castanon, Nathalie
影响因子：
3.7
作者：
Dinel AL;André C;Aubert A;Ferreira G;Layé S;Castanon N
通讯作者：
Castanon N