Electrical Stimulation Using Conductive Polymer Polypyrrole Counters Reduced Neurite Outgrowth of Primary Prefrontal Cortical Neurons from NRG1-KO and DISC1-LI Mice

Zhang, Qingsheng; Esrafilzadeh, Dorna; Crook, Jeremy Micah; Kapsa, Robert M. I.; Stewart, Elise M.; Tomaskovic-Crook, Eva; Wallace, Gordon G.; Huang, Xu‐Feng

doi:10.1038/srep42525

Cited by 30 publications

(37 citation statements)

References 29 publications

(39 reference statements)

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“…DISC1 polymorphisms have also been linked to impaired migration 85 , and DISC1 phosphorylation has been liked to a switch from NPC proliferation to migration 86 . In rodents, DISC1 polymorphisms or mutation have been linked to decreased neurite length in vivo 47 , 87 and in primary neuronal cultures 88 . DISC1 has been linked to neurite outgrowth in immortalized rodent cell cultures, with proposed mechanisms of interactions with NDEL1, FEZ1, DBZ, or dysbindin 46 , 50 , 81 , 91 – 93 .…”

Section: Discussionmentioning

confidence: 99%

Convergence of independent DISC1 mutations on impaired neurite growth via decreased UNC5D expression

et al. 2018

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The identification of convergent phenotypes in different models of psychiatric illness highlights robust phenotypes that are more likely to be implicated in disease pathophysiology. Here, we utilize human iPSCs harboring distinct mutations in DISC1 that have been found in families with major mental illness. One mutation was engineered to mimic the consequences on DISC1 protein of a balanced translocation linked to mental illness in a Scottish pedigree; the other mutation was identified in an American pedigree with a high incidence of mental illness. Directed differentiation of these iPSCs using NGN2 expression shows rapid conversion to a homogenous population of mature excitatory neurons. Both DISC1 mutations result in reduced DISC1 protein expression, and show subtle effects on certain presynaptic proteins. In addition, RNA sequencing and qPCR showed decreased expression of UNC5D, DPP10, PCDHA6, and ZNF506 in neurons with both DISC1 mutations. Longitudinal analysis of neurite outgrowth revealed decreased neurite outgrowth in neurons with each DISC1 mutation, which was mimicked by UNC5D knockdown and rescued by transient upregulation of endogenous UNC5D. This study shows a narrow range of convergent phenotypes of two mutations found in families with major mental illness, and implicates dysregulated netrin signaling in DISC1 biology.

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Section: Discussionmentioning

confidence: 99%

Convergence of independent DISC1 mutations on impaired neurite growth via decreased UNC5D expression

et al. 2018

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“…The electrodes were then rinsed with water and dried in a vacuum oven overnight at 50 °C. The choice of conductive polymer as coating material was based on our previous experiments in 2D 10 , 11 .…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that electroactive polypyrrole (PPy) doped with dodecylbenzenesulfonic acid (DBSA) promotes neuronal induction, including neurite outgrowth and branching in primary cortical neuronal cultures from normal and disease model animals 10 , 11 , as well as in human neural stem cells 12 . However, these applications are based on a two-dimensional (2D) cell culture system, while neural tissues are actually three-dimensional (3D) structures 13 .…”

Section: Introductionmentioning

confidence: 99%

Electrical Stimulation with a Conductive Polymer Promotes Neurite Outgrowth and Synaptogenesis in Primary Cortical Neurons in 3D

Zhang

Beirne

Shu

et al. 2018

Sci Rep

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Deficits in neurite outgrowth and synaptogenesis have been recognized as an underlying developmental aetiology of psychosis. Electrical stimulation promotes neuronal induction including neurite outgrowth and branching. However, the effect of electrical stimulation using 3D electrodes on neurite outgrowth and synaptogenesis has not been explored. This study examined the effect of 3D electrical stimulation on 3D primary cortical neuronal cultures. 3D electrical stimulation improved neurite outgrowth in 3D neuronal cultures from both wild-type and NRG1-knockout (NRG1-KO) mice. The expression of synaptophysin and PSD95 were elevated under 3D electrical stimulation. Interestingly, 3D electrical stimulation also improved neural cell aggregation as well as the expression of PSA-NCAM. Our findings suggest that the 3D electrical stimulation system can rescue neurite outgrowth deficits in a 3D culturing environment, one that more closely resembles the in vivo biological system compared to more traditionally used 2D cell culture, including the observation of cell aggregates as well as the upregulated PSA-NCAM protein and transcript expression. This study provides a new concept for a possible diagnostic platform for neurite deficits in neurodevelopmental diseases, as well as a viable platform to test treatment options (such as drug delivery) in combination with electrical stimulation.

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“…Polypyrrole can not only upregulate the growth factors, but can also downregulate them. Zhang et al [ 79 ] investigated the effect of a polypyrrole substrate on neuregulin-1 (NRG1) in a case of schizophrenia. The NRG1 modulated the neurite outgrowth, including the plasticity of the neural connection, and differentiation of neural stem cells.…”

Section: Materials For Neural Mps Designmentioning

confidence: 99%

Microphysiological Systems for Neurodegenerative Diseases in Central Nervous System

Bae

Jang

et al. 2020

Micromachines

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Neurodegenerative diseases are among the most severe problems in aging societies. Various conventional experimental models, including 2D and animal models, have been used to investigate the pathogenesis of (and therapeutic mechanisms for) neurodegenerative diseases. However, the physiological gap between humans and the current models remains a hurdle to determining the complexity of an irreversible dysfunction in a neurodegenerative disease. Therefore, preclinical research requires advanced experimental models, i.e., those more physiologically relevant to the native nervous system, to bridge the gap between preclinical stages and patients. The neural microphysiological system (neural MPS) has emerged as an approach to summarizing the anatomical, biochemical, and pathological physiology of the nervous system for investigation of neurodegenerative diseases. This review introduces the components (such as cells and materials) and fabrication methods for designing a neural MPS. Moreover, the review discusses future perspectives for improving the physiological relevance to native neural systems.

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Electrical Stimulation Using Conductive Polymer Polypyrrole Counters Reduced Neurite Outgrowth of Primary Prefrontal Cortical Neurons from NRG1-KO and DISC1-LI Mice

Cited by 30 publications

References 29 publications

Convergence of independent DISC1 mutations on impaired neurite growth via decreased UNC5D expression

Convergence of independent DISC1 mutations on impaired neurite growth via decreased UNC5D expression

Electrical Stimulation with a Conductive Polymer Promotes Neurite Outgrowth and Synaptogenesis in Primary Cortical Neurons in 3D

Microphysiological Systems for Neurodegenerative Diseases in Central Nervous System

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