title: Lithium/Valproic acid combination and L-glutamate induce similar pattern of changes in the expression of miR-30a-5p in SH-SY5Y neuroblastoma cells.
abstract: It has been proposed that Lithium (Li) and valproic acid (VPA) may be useful to treat neurodegenerative disorders because they protect neurons against excitotoxic insults both in vitro and in vivo models. Moreover, these two drugs may exert their effects by regulating microRNAs (miRNAs), single-stranded and non-coding RNAs able to control gene expression. A subset of the miR-30a family (miR-30a-5p) is involved in the fine-tuning of neuroprotective molecules such as the neurotrophin brain-derived neurotrophic factor (BDNF). Thus, there is the possibility that Li and VPA may alter miR-30a-5p and in turn affect BDNF production. However, data on miR-30a-5p levels in presence of Li and VPA and/or a neurotoxic insult are not yet available. Thus, the aim of this study was to investigate whether exposure to Li and VPA may influence miR-30a-5p expression in an in vitro model of neurodegeneration generated by the exposure of a human neuroblastoma cell line (SH-SY5Y) to neurotoxic concentration of L-glutamate. The results showed that both L-glutamate and Li-VPA caused an increase in miR-30a-5p expression at 24 h of incubation and a decrease at 48 h. Moreover, Li-VPA alone caused a decrease in miR-30a-5p expression also in cells not exposed to the toxic effect of glutamate. These data indicate that changes in miR-30a-5p expression induced by Li-VPA are not related to the cytoprotective action of BDNF and suggest alternative function for this miR. These findings also indicate that miRNA changes are present in in vitro models of neurodegeneration, although the significance of these changes warrants further investigation.
authors.affiliation: Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, 00179, Rome, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Croce
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelucci
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D008094:Lithium / Q000008:administration & dosage / Q000494:pharmacology*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018698:Glutamic Acid; D014635:Valproic Acid; C579455:BDNF protein, human; D008094:Lithium