Phosphodiesterase-3B is expressed in proopiomelanocortin and neuropeptide Y neurons in the mouse hypothalamus.
Phosphodiesterase-3B is expressed in proopiomelanocortin and neuropeptide Y neurons in the mouse hypothalamus.
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DOI：
10.1016/j.neulet.2011.09.068
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发表时间：
2011-11-14
影响因子：
2.5
通讯作者：
Sahu A
中科院分区：
文献类型：
--
作者：
Sahu M;Litvin DG;Sahu A
下丘脑中的瘦素信号对于正常的食物摄入和体重平衡是必不可少的。现在已经确定，除了信号换能器和转录-3激活器（STAT3）途径外，还有几种非STAT3途径介导下丘脑的瘦素信号传导。我们之前已经证明，瘦素刺激下丘脑的磷酸二酯酶3b （PDE3B）活性，而PDE3抑制剂西洛胺逆转了瘦素的厌食和减肥作用。最近，我们已经证明西洛胺逆转了瘦素诱导的下丘脑POMC基因表达的增加。由于POMC和神经肽Y （NPY）神经元被认为是下丘脑瘦素信号传导的主要靶点，因此要确定PDE3B通路的生理作用，证明PDE3B是否在这些神经元中表达是很重要的。为此，我们分别在POMC- gfp和NPY- gfp小鼠中使用免疫细胞化学方法检测了PDE3B与POMC和NPY神经元的共定位。结果显示PDE3B高度定位于下丘脑的各个部位，包括弓状核（ARC）、腹内侧核、背内侧核、腹侧乳头前核、室旁核和外侧下丘脑。重要的是，几乎所有的NPY（91.7%）和POMC（97.7%）神经元共同表达PDE3B。这些结果提示PDE3B通路在POMC和NPY神经元中介导瘦素信号传导的直接作用，这是下丘脑瘦素信号传导的潜在机制。
Leptin signaling in the hypothalamus is obligatory for normal food intake and body weight homeostasis. It is now well established that besides the signal transducer and activator of transcription-3 (STAT3) pathway, several non-STAT3 pathways mediate leptin signaling in the hypothalamus. We have previously demonstrated that leptin stimulates phosphodiesterase-3B (PDE3B) activity in the hypothalamus, and PDE3 inhibitor cilostamide reverses anorectic and bodyweight reducing effects of leptin. Recently, we have demonstrated that cilostamide reversed the leptin-induced increase in proopiomelanocortin (POMC) gene expression in the hypothalamus. Because POMC and neuropeptide Y (NPY) neurons are thought to be the major targets of leptin signaling in the hypothalamus, to establish the physiological role of the PDE3B pathway it is important to demonstrate if PDE3B is expressed in these neurons. To this end we examined co-localization of PDE3B with POMC and NPY neurons using immunocytochemistry in POMC-GFP and NPY-GFP mice, respectively. Results showed that PDE3B was highly localized throughout the various hypothalamic sites including the arcuate nucleus (ARC), ventromedial nucleus, dorsomedial nucleus, ventral premammillary nucleus, paraventricular nucleus, and lateral hypothalamus. Importantly, almost all NPY (91.7%) and POMC (97.7%) neurons co-expressed PDE3B. These results suggest a direct role of the PDE3B pathway in mediating leptin signaling in the POMC and NPY neurons –a potential mechanism of leptin signaling in the hypothalamus.
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影响因子：
56.9
作者：
Cota, D;Proulx, K;Seeley, RJ
通讯作者：
Seeley, RJ
DOI：
10.1073/pnas.93.13.6231
发表时间：
1996-06-25
影响因子：
11.1
作者：
Ghilardi, N;Ziegler, S;Skoda, RC
通讯作者：
Skoda, RC
影响因子：
16.2
作者：
Elias, CF;Aschkenasi, C;Elmquist, JK
通讯作者：
Elmquist, JK
影响因子：
7.7
作者：
Baskin, DG;Breininger, JF;Schwartz, MW
通讯作者：
Schwartz, MW
影响因子：
64.8
作者：
Niswender, KD;Morton, GJ;Schwartz, MW
通讯作者：
Schwartz, MW