In Vitro Cortical Networks for Disease Modeling and Drug Evaluation Metadata

Title

• Main Title In Vitro Cortical Networks for Disease Modeling and Drug Evaluation

Creator

• Author: Wu, Calvin
  Creator Type: Personal

Contributor

• Chair: Gross, Guenter W.
  Contributor Type: Personal
  Contributor Info: Major Professor
• Chair: Moore, Ernest J.
  Contributor Type: Personal
  Contributor Info: Co-Major Professor
• Committee Member: Fuchs, Jannon
  Contributor Type: Personal
• Committee Member: Gopal, Kamakshi
  Contributor Type: Personal
• Committee Member: Schwark, Harris
  Contributor Type: Personal

Publisher

• Name: University of North Texas
  Place of Publication: Denton, Texas
  Additional Info: www.unt.edu

Date

• Creation: 2013-12

Language

• English

Description

• Content Description: In translational research, disease models in preclinical studies are used as media for discovery of drugs or novel therapeutics. Development of in vitro models for various neurological diseases that enable efficient pharmacological or toxicological screening has been ongoing but challenging. Recognizing the potential benefit of in vitro disease models, dysfunctions in the cortical neuronal networks were induced to mimic the functional pathology of neurological symptoms using microelectrode arrays. Two different disease states – tinnitusand excitotoxicity – were investigated and discussed. In this model, pentylenetetrazol-induced increase in spontaneous firing rate and synchrony in the auditory cortical networks was used as correlate of tinnitus. Potential tinnitus treatment drugs from several different classes – including the novel class of potassium channel openers – were screened and quantified. The potentialtherapeutic values of these drugs were also discussed as the basis for drug repurposing. Functional excitotoxicity was induced by cisplatin (a cancer drug that causes neurological sideeffects) and glutamate (the major excitatory neurotransmitter). As proof-of-principle that the model may contribute to expediting the development of therapeutics, cisplatin excitotoxicity wasprevented by the antioxidant D-methionine, while glutamate excitotoxicity was prevented by ceftriaxone (a modulator of a glutamate reuptake transporter). In the latter part of the study, with results linking two of the screened drugs L-carnitine and D-methionine to GABAA receptor activation, it was demonstrated that this model not only served as an efficient drug-screening platform, but can be utilized to functionally investigate the underlying mechanism of drugs. Inaddition, several practical or conceptual directions for future studies to improve on this in vitro disease model are suggested.

Subject

• Keyword: Microelectrode array
• Keyword: primary neuronal culture
• Keyword: neurotoxicity drug screening
• Keyword: tinnitus model
• Keyword: neuronal network

Collection

• Name: UNT Theses and Dissertations
  Code: UNTETD

Institution

• Name: UNT Libraries
  Code: UNT

Rights

• Rights Access: public
• Rights Holder: Wu, Calvin
• Rights License: copyright
• Rights Statement: Copyright is held by the author, unless otherwise noted. All rights Reserved.

Resource Type

• Thesis or Dissertation

Format

• Text

Identifier

• Archival Resource Key: ark:/67531/metadc407860

Degree

• Academic Department: Department of Speech and Hearing Sciences
• Degree Discipline: Biological Sciences
• Degree Level: Master's
• Degree Name: Doctor of Philosophy
• Degree Publication Type: thesi
• Degree Grantor: University of North Texas

Note