Undergraduate Research Program, Centre College, USA.
Psychiatry Res. 2010 Jul 30;178(2):391-4. doi: 10.1016/j.psychres.2009.10.019. Epub 2010 May 15.
Low levels of brain-derived neurotrophic factor (BDNF) peptide are linked to the pathophysiology of mood disorders. Several single-nucleotide polymorphisms (SNPs) across the BDNF gene (BDNF) have been associated with bipolar illness. Since both elevated intracellular sodium and apoptosis are believed to contribute to cellular dysfunction in bipolar disorder, it is important to determine the effect of exogenous BDNF on apoptosis induced by the high levels of intracellular sodium seen in ill bipolar patients. Human olfactory neuroepithelial progenitor cells were treated with monensin, a sodium ionophore that increases intracellular sodium and leads to apoptosis. Apoptosis was quantified with enzyme-linked immunosorbent assay (ELISA) for mono- and oligonucleosomes. Elevation of intracellular sodium concentration by monensin induced apoptosis. BDNF 100ng/mL pretreatment or co-treatment attenuated the monensin-induced apoptosis. Pretreatment with BDNF for 24h reduced monensin-induced apoptosis by 93%. Co-treatment of BDNF and monensin increased intracellular sodium concentration and reduced apoptosis by 66%. Monensin for 24h models a process that is believed to occur during ill phases of bipolar illness. Treatment with BDNF greatly attenuates or prevents monensin-induced apoptosis. The functional consequences of BDNF SNPs, known to be associated with bipolar illness, need to be examined.
脑源性神经营养因子(BDNF)肽水平低与心境障碍的病理生理学有关。BDNF 基因(BDNF)的几个单核苷酸多态性(SNP)与双相情感障碍有关。由于细胞内钠离子升高和细胞凋亡被认为有助于双相情感障碍中的细胞功能障碍,因此确定外源性 BDNF 对在患病双相患者中所见的高水平细胞内钠离子诱导的细胞凋亡的影响非常重要。用人嗅神经上皮祖细胞用莫能菌素处理,莫能菌素是一种钠离子载体,可增加细胞内钠离子并导致细胞凋亡。用酶联免疫吸附试验(ELISA)测定单核细胞和寡核小体的凋亡。莫能菌素升高细胞内钠离子浓度诱导细胞凋亡。BDNF 100ng/mL 预处理或共同处理可减轻莫能菌素诱导的凋亡。BDNF 预处理 24h 可使莫能菌素诱导的凋亡减少 93%。BDNF 和莫能菌素共同处理可增加细胞内钠离子浓度并减少 66%的凋亡。莫能菌素 24h 模型被认为是在双相情感障碍的发病阶段发生的过程。BDNF 的治疗可大大减轻或预防莫能菌素诱导的细胞凋亡。需要检查与双相情感障碍相关的已知与 BDNF SNP 的功能后果。