AdipoRon Treatment Induces a Dose-Dependent Response in Adult Hippocampal Neurogenesis.
AdipoRon Treatment Induces a Dose-Dependent Response in Adult Hippocampal Neurogenesis.
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AdipoRon 治疗在成人海马神经发生中诱导剂量依赖性反应
DOI：
10.3390/ijms22042068
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发表时间：
2021-02-19
影响因子：
5.6
通讯作者：
Yau SY
中科院分区：
文献类型：
--
作者：
Lee TH;Christie BR;van Praag H;Lin K;Siu PM;Xu A;So KF;Yau SY
脂联素受体激动剂AdipoRon在小鼠模型上引起与脂联素相似的抗糖尿病、抗动脉粥样硬化和抗炎作用。由于AdipoRon可以穿越血脑屏障，其对调节海马区功能的慢性影响尚未得到检验。本研究调查了AdipoRon治疗是否以剂量依赖的方式促进海马神经发生和空间再认记忆。给青春期雄性C57BL/6J小鼠连续给予20 mg/kg(低剂量)或50 mg/kg(高剂量)AdipoRon或赋形剂14天后，用旷场实验检测焦虑和运动能力，用Y迷宫实验检测海马依赖的空间再认记忆。对海马齿状回神经前体细胞、未成熟神经元和新生细胞的免疫阳性细胞标记物进行了定量。免疫吸附分析法检测血清中脂联素、脑源性神经营养因子和皮质酮等调节海马神经发生的因子水平。结果表明，20 mg/kg AdipoRon可显著促进大鼠海马细胞增殖，提高血清脂联素和脑源性神经营养因子水平，但对空间再认记忆和运动能力无明显影响。相反，50 mg/kg AdipoRon治疗可损害空间识别记忆，抑制细胞增殖、神经元分化和细胞存活，并伴随血清BDNF和脂联素水平的降低。结果表明，低剂量的AdipoRon治疗促进了海马细胞的增殖，而高剂量的AdipoRon治疗对海马区的功能不利。
AdipoRon, an adiponectin receptor agonist, elicits similar antidiabetic, anti-atherogenic, and anti-inflammatory effects on mouse models as adiponectin does. Since AdipoRon can cross the blood-brain barrier, its chronic effects on regulating hippocampal function are yet to be examined. This study investigated whether AdipoRon treatment promotes hippocampal neurogenesis and spatial recognition memory in a dose-dependent manner. Adolescent male C57BL/6J mice received continuous treatment of either 20 mg/kg (low dose) or 50 mg/kg (high dose) AdipoRon or vehicle intraperitoneally for 14 days, followed by the open field test to examine anxiety and locomotor activity, and the Y maze test to examine hippocampal-dependent spatial recognition memory. Immunopositive cell markers of neural progenitor cells, immature neurons, and newborn cells in the hippocampal dentate gyrus were quantified. Immunosorbent assays were used to measure the serum levels of factors that can regulate hippocampal neurogenesis, including adiponectin, brain-derived neurotrophic factor (BDNF), and corticosterone. Our results showed that 20 mg/kg AdipoRon treatment significantly promoted hippocampal cell proliferation and increased serum levels of adiponectin and BDNF, though there were no effects on spatial recognition memory and locomotor activity. On the contrary, 50 mg/kg AdipoRon treatment impaired spatial recognition memory, suppressed cell proliferation, neuronal differentiation, and cell survival associated with reduced serum levels of BDNF and adiponectin. The results suggest that a low-dose AdipoRon treatment promotes hippocampal cell proliferation, while a high-dose AdipoRon treatment is detrimental to the hippocampus function.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
15.9
作者：
KNITTLE, JL;TIMMERS, K;KATZ, DP
通讯作者：
KATZ, DP
影响因子：
4.6
作者：
Kim MW;Abid NB;Jo MH;Jo MG;Yoon GH;Kim MO
通讯作者：
Kim MO
影响因子：
7.6
作者：
Hare, Brendan D.;Beierle, Jacob A.;Falls, William A.
通讯作者：
Falls, William A.
DOI：
10.1073/pnas.1206171109
发表时间：
2012-05-29
影响因子：
11.1
作者：
Busche, Marc Aurel;Chen, Xiaowei;Konnerth, Arthur
通讯作者：
Konnerth, Arthur