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Increased brain vitamin D receptor expression and decreased expression of cathelicidin antimicrobial peptide in individuals who died by suicide.
Journal of Psychiatric Research ( IF 4.8 ) Pub Date : 2020-02-27 , DOI: 10.1016/j.jpsychires.2020.02.027
Teodor T Postolache 1 , Faisal Akram 2 , Ellen E Lee 3 , Christopher A Lowry 4 , John W Stiller 5 , Lisa A Brenner 6 , Elizabeth A Streeten 7 , Gustavo Turecki 8 , Yogesh Dwivedi 9
Affiliation  

Vitamin D deficiency is associated with immune dysregulation, increased vulnerability to infections, depression, and suicidal behavior. One mediator of vitamin D-dependent immune regulation and antimicrobial defense is the cathelicidin antimicrobial peptide (LL-37), encoded by the cathelicidin-related antimicrobial peptide (CRAMP) gene. We compared the mRNA expression of the CRAMP gene, the vitamin D receptor (VDR) gene, as well as the CYP27B1 and CYP24A1 genes (involved in vitamin D metabolism) in the dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC) between depressed individuals who died by suicide (n = 15) and matched (age, gender, and post-mortem interval) non-psychiatric controls (n = 15). Gene expression was measured through qRT-PCR with TaqMan® primers and probes, with GAPDH and β-actin genes as endogenous controls. Statistical analyses included t-tests and Pearson correlations. CRAMP mRNA expression was downregulated and VDR mRNA expression was upregulated in both dlPFC and ACC in suicides relative to controls, with no significant differences in expression of CYP24A1 and CYP27B1. To our knowledge, this is the first study on brain cathelicidin expression in the human brain in relationship to suicide. Increased VDR and decreased CRAMP expression are consistent with previously reported associations between vitamin D deficiency, immune dysregulation, and suicidal behavior, and should lead to future studies uncovering novel interactive targets for suicide prevention.

中文翻译:

自杀死亡的人脑维生素D受体表达增加,而cathelicidin抗菌肽的表达降低。

维生素D缺乏症与免疫功能异常,感染,抑郁症和自杀行为的易感性增加有关。维生素D依赖的免疫调节和抗菌素防御的一种介体是cathelicidin抗菌肽(LL-37),由cathelicidin相关的抗菌肽(CRAMP)基因编码。我们比较了CRAMP基因,维生素D受体(VDR)基因以及CYP27B1和CYP24A1基因(涉及维生素D代谢)在背外侧前额叶皮层(dlPFC)和前扣带回皮层(ACC)之间的mRNA表达。因自杀死亡(n = 15)并与非精神病控制者(年龄,性别和验尸间隔)相匹配(n = 15)的抑郁症患者。通过qRT-PCR,使用TaqMan®引物和探针,以GAPDH和β-肌动蛋白基因作为内源性对照,测量基因表达。统计分析包括t检验和Pearson相关性。相对于对照组,自杀的dlPFC和ACC中CRAMP mRNA表达下调,VDR mRNA表达上调,CYP24A1和CYP27B1的表达无明显差异。据我们所知,这是关于人脑中脑钙调素表达与自杀关系的第一项研究。VDR增加和CRAMP表达降低与先前报道的维生素D缺乏症,免疫失调和自杀行为之间的关联相一致,并且应该导致未来的研究发现新的预防自杀的相互作用靶标。CYP24A1和CYP27B1的表达无明显差异。据我们所知,这是关于人脑中脑钙调素表达与自杀关系的第一项研究。VDR增加和CRAMP表达降低与先前报道的维生素D缺乏症,免疫失调和自杀行为之间的关联相一致,并且应该导致未来的研究发现新的预防自杀的相互作用靶标。CYP24A1和CYP27B1的表达无明显差异。据我们所知,这是关于人脑中脑钙调素表达与自杀关系的第一项研究。VDR增加和CRAMP表达降低与先前报道的维生素D缺乏症,免疫失调和自杀行为之间的关联相一致,并且应该导致未来的研究发现新的预防自杀的相互作用靶标。
更新日期:2020-02-27
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