title: Effects of brain-derived neurotrophic factor on sodium-induced apoptosis in human olfactory neuroepithelial progenitor cells.
abstract: 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.
authors.affiliation: Undergraduate Research Program, Centre College, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Willett
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Gao
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: Lei
authors.forename: Chengling
authors.initials: C
authors.lastname: Lu
authors.forename: Fred J
authors.initials: FJ
authors.lastname: Roisen
authors.forename: Welby I
authors.initials: WI
authors.lastname: Winstead
authors.forename: Rif S
authors.initials: RS
authors.lastname: El-Mallakh
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008985:Monensin / Q000494:pharmacology; D046569:Neuroepithelial Cells / Q000187:drug effects*; D009830:Olfactory Bulb / Q000166:cytology*; D013234:Stem Cells / Q000187:drug effects*; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007476:Ionophores; D008985:Monensin