Hellsten Sofie V, Eriksson Mikaela M, Lekholm Emilia, Arapi Vasiliki, Perland Emelie, Fredriksson Robert
Department of Pharmaceutical Bioscience, Molecular Neuropharmacology, Uppsala University, Uppsala SE, Sweden.
PLoS One. 2017 Feb 24;12(2):e0172917. doi: 10.1371/journal.pone.0172917. eCollection 2017.
SLC38A9 is characterized as a lysosomal component of the amino acid sensing Ragulator-RAG GTPase complex, controlling the mechanistic target of rapamycin complex 1 (mTORC1). Here, immunohistochemistry was used to map SLC38A9 in mouse brain and staining was detected throughout the brain, in cortex, hypothalamus, thalamus, hippocampus, brainstem and cerebellum. More specifically, immunostaining was found in areas known to be involved in amino acid sensing and signaling pathways e.g. piriform cortex and hypothalamus. SLC38A9 immunoreactivity co-localized with both GABAergic and glutamatergic neurons, but not with astrocytes. SLC38A9 play a key role in the mTORC1 pathway, and therefore we performed in vivo starvation and high-fat diet studies, to measure gene expression alterations in specific brain tissues and in larger brain regions. Following starvation, Slc38a9 was upregulated in brainstem and cortex, and in anterior parts of the brain (Bregma 3.2 to -2.1mm). After high-fat diet, Slc38a9 was specifically upregulated in hypothalamus, while overall downregulation was noticed throughout the brain (Bregma 3.2 to -8.6mm).
溶质载体家族38成员9（SLC38A9）被鉴定为氨基酸感应Ragulator-RAG GTP酶复合物的溶酶体成分，可控制雷帕霉素复合物1（mTORC1）的作用机制靶点。在此，采用免疫组织化学方法对小鼠脑内的SLC38A9进行定位，结果在整个脑内均检测到染色，包括皮质、下丘脑、丘脑、海马、脑干和小脑。更具体地说，在已知参与氨基酸感应和信号通路的区域，如梨状皮质和下丘脑，发现了免疫染色。SLC38A9免疫反应性与γ-氨基丁酸能（GABAergic）和谷氨酸能神经元共定位，但与星形胶质细胞不共定位。SLC38A9在mTORC1通路中起关键作用，因此我们进行了体内饥饿和高脂饮食研究，以测量特定脑组织和较大脑区的基因表达变化。饥饿后，Slc38a9在脑干和皮质以及脑前部（前囟3.2至-2.1毫米）上调。高脂饮食后，Slc38a9在下丘脑特异性上调，而在整个脑（前囟3.2至-8.6毫米）中则出现整体下调。
