Contributions of Metallo-Beta-Lactamase Domain Containing Protein 1 (MBLAC1) to the Neurobiological Actions of Ceftriaxone
dc.creator | Retzlaff, Cassandra Lynn | |
dc.date.accessioned | 2020-08-23T15:48:53Z | |
dc.date.available | 2018-11-29 | |
dc.date.issued | 2017-11-29 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-11202017-102425 | |
dc.identifier.uri | http://hdl.handle.net/1803/14672 | |
dc.description.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. | |
dc.format.mimetype | application/pdf | |
dc.subject | Ceftriaxone | |
dc.subject | Glutamate | |
dc.subject | MBLAC1 | |
dc.title | Contributions of Metallo-Beta-Lactamase Domain Containing Protein 1 (MBLAC1) to the Neurobiological Actions of Ceftriaxone | |
dc.type | dissertation | |
dc.contributor.committeeMember | Tina Iverson | |
dc.contributor.committeeMember | Randy Blakely | |
dc.contributor.committeeMember | Brian Wadzinkski | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Neuroscience | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2018-11-29 | |
local.embargo.lift | 2018-11-29 | |
dc.contributor.committeeChair | Roger Colbran |
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