title: Electrical Stimulation Using Conductive Polymer Polypyrrole Counters Reduced Neurite Outgrowth of Primary Prefrontal Cortical Neurons from NRG1-KO and DISC1-LI Mice.
abstract: Deficits in neurite outgrowth, possibly involving dysregulation of risk genes neuregulin-1 (NRG1) and disrupted in schizophrenia 1 (DISC1) have been implicated in psychiatric disorders including schizophrenia. Electrical stimulation using conductive polymers has been shown to stimulate neurite outgrowth of differentiating human neural stem cells. This study investigated the use of the electroactive conductive polymer polypyrrole (Ppy) to counter impaired neurite outgrowth of primary pre-frontal cortical (PFC) neurons from NRG1-knock out (NRG1-KO) and DISC1-locus impairment (DISC1-LI) mice. Whereas NRG1-KO and DISC1-LI exhibited reduced neurite length and number of neurite branches compared to wild-type controls, this was not apparent for cultures on electroactive Ppy. Additionally, the use of the Ppy substrate normalised the synaptophysin and PSD95 protein and mRNA expression whereas both are usually reduced by NRG1-KO or DISC1-LI. Our findings support the utility of Ppy mediated electrical stimulation to prevent the reduction of neurite outgrowth and related synaptic protein expression in the primary PFC neurons from NRG1-KO and DISC1-LI mice, providing proof-of-concept for treating neurodevelopmental diseases including schizophrenia.
authors.affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia.|ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, NSW 2519, Australia.|Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, NSW 2519, Australia.|Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
authors.forename: Dorna
authors.initials: D
authors.lastname: Esrafilzadeh
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, NSW 2519, Australia.|Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.|Departments of Surgery, St Vincent's Hospital, The University of Melbourne, Fitzroy, VIC 3065, Australia.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Crook
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, NSW 2519, Australia.|Departments of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, VIC 3065, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Kapsa
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, NSW 2519, Australia.
authors.forename: Elise M
authors.initials: EM
authors.lastname: Stewart
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, NSW 2519, Australia.|Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
authors.forename: Eva
authors.initials: E
authors.lastname: Tomaskovic-Crook
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, NSW 2519, Australia.
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Wallace
authors.affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia.|Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.|Schizophrenia Research Institute, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Huang
mesh_terms: D000818:Animals; D015415:Biomarkers; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation; D005455:Fluorescent Antibody Technique; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D020890:Neuregulin-1 / Q000172:deficiency*; D000071446:Neuronal Outgrowth; D009474:Neurons / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C498794:Disc1 protein, mouse; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D012333:RNA, Messenger; D016708:Synaptophysin