Contributions of Metallo-Beta-Lactamase Domain Containing Protein 1 (MBLAC1) to the Neurobiological Actions of Ceftriaxone
Cassandra Lynn Retzlaff
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Dissertation under the direction of Professor Randy Blakely, PhD
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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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-11202017-102425 |
| Date | 29 November 2017 |
| Creators | Retzlaff, Cassandra Lynn |
| Contributors | Roger Colbran, Tina Iverson, Randy Blakely, Brian Wadzinkski |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-11202017-102425/ |
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