人类前额叶皮层中鸟苷酸环化酶 C 的表达取决于性别和进食状态

IF 3.5 3区 医学 Q2 NEUROSCIENCES Frontiers in Molecular Neuroscience Pub Date : 2024-05-22 DOI:10.3389/fnmol.2024.1361089
Martina Ratko, Vladiana Crljen, Martina Tkalčić, Anton Mažuranić, Pero Bubalo, Petar Škavić, Ivan Banovac, Aleksandra Dugandžić
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引用次数: 0

摘要

在啮齿类动物大脑皮层、杏仁核、中脑、下丘脑和小脑的神经元中检测到了鸟苷酸环化酶 C(GC-C)。在本研究中,我们通过酶联免疫吸附法测定了人类前额叶皮层布罗德曼区(BA)9、BA10、BA11和BA32中参与摄食行为调节的GC-C蛋白表达,以及小脑皮层、下丘脑弓状核和黑质中GC-C蛋白的表达。在雄性BA11和BA10-M中,GC-C的表达受进食的调节,尸检时GC-C的表达与胃内容物的体积呈负相关。在雌性 BA11 中未发现相关性,而在 BA10-M 中甚至发现了正相关性。这表明在 BA11 和 BA10-M 中,GC-C 的表达调节存在性别差异。只有在餐后不久死亡时,雌性 BA9 的 GC-C 含量才较高,而 BA10-O 只有在空腹时 GC-C 的表达量才较高。与男性下丘脑相比,雌性下丘脑中 GC-C 的表达量仅在胃部饱满时较低,这表明 GC-C 激动剂对女性的饱腹效应可能较低。由于这是首次研究 GC-C 在前额叶皮质中的调节作用及其可能的功能,因此要确定 GC-C 在前额叶皮质不同区域(尤其是在人类中)的确切作用,还需要进一步的研究。
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Expression of guanylate cyclase C in human prefrontal cortex depends on sex and feeding status
Guanylate cyclase C (GC-C) has been detected in the rodent brain in neurons of the cerebral cortex, amygdala, midbrain, hypothalamus, and cerebellum.In this study we determined GC-C protein expression in Brodmann areas (BA) 9, BA10, BA11, and BA32 of the human prefrontal cortex involved in regulation of feeding behavior, as well as in the cerebellar cortex, arcuate nucleus of hypothalamus and substantia nigra in brain samples of human 21 male and 13 female brains by ELISA with postmortem delay < 24 h.GC-C was found in all tested brain areas and it was expressed in neurons of the third cortical layer of BA9. The regulation of GC-C expression by feeding was found in male BA11 and BA10-M, where GC-C expression was in negative correlation to the volume of stomach content during autopsy. In female BA11 there was no correlation detected, while in BA10-M there was even positive correlation. This suggests sex differences in GC-C expression regulation in BA11 and BA10-M. The amount of GC-C was higher in female BA9 only when the death occurred shortly after a meal, while expression of GC-C was higher in BA10-O only when the stomach was empty. The expression of GC-C in female hypothalamus was lower when compared to male hypothalamus only when the stomach was full, suggesting possibly lower satiety effects of GC-C agonists in women.These results point toward the possible role of GC-C in regulation of feeding behavior. Since, this is first study of GC-C regulation and its possible function in prefrontal cortex, to determine exact role of GC-C in different region of prefrontal cortex, especially in humans, need further studies.
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来源期刊
CiteScore
5.70
自引率
2.10%
发文量
669
审稿时长
14 weeks
期刊介绍: Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.
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