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cyclic amp response element-binding protein
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     Morphological changes of cyclic AMP response element binding protein positive neurons in hypothalamus following ovariectomy in female rats
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  cyclic amp response element-binding protein
Cyclic AMP response element-binding protein (CREB) is a 43-kDa polypeptide that binds a cAMP response element located at the 5' promoter region of cAMP regulatory genes.
      
Here, we have examined the effects of CsA on the DNA-binding activity of the cyclic AMP response element-binding protein (CREB) and cell viability, and the effects of CREB on cathepsin B and L synthesis and activity in HGFs.
      
From the gene map of the HLA region, the cyclic AMP response element-binding protein-related protein gene (CREB-RP) appeared to be located at the telomeric end in the 50-kb region.
      


The normal visual input is vital for the development and modification of primary visual cortex and visual development is typified by a critical period when manipulating input will cause dramatic changes in cortical connectivity. The pivotal role of transcription factor cyclic AMP response element binding protein (CREB) in signal transduction pathways, together with its function in physiological activities of long-term synaptic plasticity in a variety of organisms, suggests that CREB might...

The normal visual input is vital for the development and modification of primary visual cortex and visual development is typified by a critical period when manipulating input will cause dramatic changes in cortical connectivity. The pivotal role of transcription factor cyclic AMP response element binding protein (CREB) in signal transduction pathways, together with its function in physiological activities of long-term synaptic plasticity in a variety of organisms, suggests that CREB might be involved in the mechanisms that play important roles in the visual cortex development. Therefore in the present study, we applied specific antibodies recognizing CREB to the primary visual cortex at P14, P22, P30, P45 and P90 and investigated CREB immunoreactivity in the Sprague-Dawley rat visual cortex at a range of developmental stages. The results from the immunohistochemistry and Western blot experiments demonstrated that the CREB protein expression changes with normal visual development and the CREB immunoreactivity peaked in layers Ⅱ-Ⅵ during the critical period. These results indicate that there is correlation between CREB protein expression and the time course of normal visual development. How these changes of immunoreactivity relate to synaptic transmission and plasticity needs to be further clarified.

正常视觉信息输入对初期视皮层的发育和修饰至关重要。视觉发育的特点是存在一个关键期 ,在此期内控制信息输入将导致皮质联系的显著变化。转录因子 -c AMP反应元件结合蛋白 ( CREB)在多种有机体的信号传导通路中的枢纽作用和其参与长时程突触可塑性的生理活动提示 ,它可能参与了在视皮层发育中发挥重要作用的分子机制。本研究应用免疫组织化学方法和 Western blot技术 ,对 P14、P2 2、P3 0、P45和 P90年龄组 Sprague-Dawley大鼠视皮层内 CREB的免疫反应性进行观察和分析。结果证明 ,CREB在视皮层各层内的蛋白表达时程与视觉发育的关键期一致 ,其免疫反应性在 P2 2至 P45期间达到高水平 ,成年后的蛋白表达出现下调。结论 :视觉可塑性降低的同时存在 CREB表达的显著改变 ,但该蛋白表达改变与突触传递和可塑性的关系尚待阐明

At present, the characteristics of synaptic plasticity have been known to a great extent, but the potential molecular mechanisms underlying this developmental neuronal plasticity remain to be clarified. A series of studies have suggested that cyclic AMP response element binding protein (CREB) is involved in the regulation of long-term synaptic plasticity in the course of learning, memory and long-term potentiation. We hypothesized that CREB will play an important role in the plasticity...

At present, the characteristics of synaptic plasticity have been known to a great extent, but the potential molecular mechanisms underlying this developmental neuronal plasticity remain to be clarified. A series of studies have suggested that cyclic AMP response element binding protein (CREB) is involved in the regulation of long-term synaptic plasticity in the course of learning, memory and long-term potentiation. We hypothesized that CREB will play an important role in the plasticity of visual system. The total CREB and phosphorylated CREB immunoreactivity in the visual cortex of monocularly deprived rats at various ages, ie, postnatal day 45 and postnatal day 90, were studied. Immunohistochemical analyses with anti-CREB and anti-phosphorylated CREB polycloned antibodies were performed on tissue sections obtained from the monocularly deprived rats and normal control ones. We found that monocular deprivation in the critical period had little effect on total CREB expression in the rat visual cortex. However, monocular deprivation determines a decrease of phosphorylated CREB immunoreactivity exclusively in the monocular segment (OC1M) area of the visual cortex contralateral to the deprived eye at postnatal day 45, especially in layers Ⅱ/Ⅲ and Ⅳ. No significant visual deprivation effect on phosphorylated CREB expression was seen in the binocular segment (OC1B) area at the same age or in the visual cortex at postnatal day 90. Our results indicate that CREB may play roles in the plasticity of visual system through its phosphorylated state.

目前已对突触可塑性的基本特性有了相当程度的认识 ,但对其发育中神经元可塑性的内在分子机制尚待进一步阐明。不少研究提示 ,c AMP反应元件结合蛋白 ( CREB)在学习、记忆和长时程增强 ( LTP)过程中参与长时程突触的可塑性调节 ,推测其在视觉系统可塑性中也发挥着重要作用。本研究通过建立幼年大鼠单眼剥夺弱视模型 ,应用免疫组织化学方法 ,对视觉发育关键期末 ( P45 )大鼠和成年 ( P90 )大鼠视皮层中 CREB和 p CREB的免疫反应性进行观察、比较和分析。结果 :视觉发育关键期内进行单眼视觉剥夺对大鼠视皮层内总 CREB的蛋白表达没有产生显著影响 ,而 p CREB在 P45大鼠的剥夺眼对侧视皮层单眼反应区的 / 、 层中的蛋白表达较剥夺眼同侧视皮层的相应区域弱 ,该差异在该年龄大鼠的双眼反应区及成年后大鼠视皮层内不存在。结论 :CREB可能通过该磷酸化形式在视觉系统可塑性中发挥作用

Objective: To study morphological changes of cyclic AMP response element binding protein (CREB) positive neurons in the preoptic area (PA) of hypothalamus following ovariectomy in female rats, and to explore the relationship between CREB and GnRH in hypothalamic secretion. Methods: Using immunocytochemistry method, we observed the distributions and cellular forms of CREB positive neurons in medical preoptic area (MPA) and lateral preoptic area (LPA) of hypothalamus and counted their...

Objective: To study morphological changes of cyclic AMP response element binding protein (CREB) positive neurons in the preoptic area (PA) of hypothalamus following ovariectomy in female rats, and to explore the relationship between CREB and GnRH in hypothalamic secretion. Methods: Using immunocytochemistry method, we observed the distributions and cellular forms of CREB positive neurons in medical preoptic area (MPA) and lateral preoptic area (LPA) of hypothalamus and counted their numbers. The quantitative analysis of the immunoreactive production in the CREB positive neurons in MPA and LPA were done with an imaging analysis system. Results: (1)Plenty of CREB positive neurons were found in MPA and LPA of hypothalamus in intact female rats. The profile of cell bodies of CREB positive neurons was clear and the staining of the nuclei of CREB positive cell was weak.(2)The densities of positive CREB neurons and the average optical densities(AOD) of positive CREB neurons had more significant increases both in the ovariectomy(OVX) 3 months group and the OVX 6 months group than that in the intact group (P<0.01). (3) There were significant differences between the AOD and the densities of positive CREB neurons in the OVX 3 months group than that in the OVX 6 months group and in LPA than in MPA (P<0.05-0.01).Conclusion: The quantity of CREB positive neurons in the preoptic area of hypothalamus following ovariectomy are more than that of the control group in a long time.

目的 :观察雌性大鼠去卵巢后 ,下丘脑视前区 (PA)内转录因子环磷酸腺苷反应元件结合蛋白 (CREB)阳性神经元的变化 ,及探讨CREB与GnRH分泌变化的关系。方法 :采用免疫细胞化学方法对下丘脑视前内侧区 (MPA)和视前外侧区 (LPA)内CREB阳性神经元进行形态观察和细胞计数 ,采用图像分析系统测定CREB阳性神经元内的免疫产物的平均光密度 (AOD)值。结果 :( 1 )大量CREB阳性神经元见于对照大鼠的LPA和MPA。 ( 2 )去卵巢后CREB阳性神经元的数目和AOD值显著增高。 ( 3 )在阳性神经元分布和阳性产物的含量上有时间和亚区差异。结论 :大鼠去卵巢后 ,在较长时间内 ,下丘脑CREB阳性神经元仍保持比对照组大鼠较多的数目

 
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