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Title page for ETD etd-11202017-102425


Type of Document Dissertation
Author Retzlaff, Cassandra Lynn
URN etd-11202017-102425
Title Contributions of Metallo-Beta-Lactamase Domain Containing Protein 1 (MBLAC1) to the Neurobiological Actions of Ceftriaxone
Degree PhD
Department Neuroscience
Advisory Committee
Advisor Name Title
Roger Colbran Committee Chair
Brian Wadzinkski Committee Member
Randy Blakely Committee Member
Tina Iverson Committee Member
Keywords
  • Ceftriaxone
  • Glutamate
  • MBLAC1
Date of Defense 2017-12-16
Availability restrictone
Abstract
Contributions of Metallo-Beta-Lactamase Domain Containing Protein 1 (MBLAC1) to the Neurobiological Actions of Ceftriaxone Cassandra Lynn Retzlaff

Dissertation under the direction of Professor Randy Blakely, PhD

Recently identified glial-expressed C. elegans gene, swip-10, encodes a metallo-beta-lactamase domain-containing protein, which limits glutamate-dependent changes in dopamine neuron excitability. Bioinformatic analyses identified MBLAC1 as the likely mammalian orthologue of swip-10. Ceftriaxone, a beta-lactam antibiotic, has been reported to act independently of its antimicrobial actions to normalize perturbed central nervous system glutamate levels, principally by elevating expression of glial glutamate transporters. Housing a canonical beta-lactam binding domain, MBLAC1, stood out as a possible molecular target for ceftriaxone, of which one is currently unknown. Using multiple approaches, evidence presented asserts the specific, high affinity binding of ceftriaxone to MBLAC1. Furthermore, the creation of a novel knockout mouse model was utilized in order to test these hypotheses in vivo, and to establish a role for MBLAC1 in the brain.

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