Evidence for improved motor function by ceftriaxone despite striatal tyrosine hydroxylase loss following nigrostriatal lesion
| dc.contributor.author | Meadows, Samantha | |
| dc.contributor.author | Cantu, Mark | |
| dc.contributor.author | Bishop, Chris | |
| dc.contributor.author | Salvatore, Michael | |
| dc.creator | Kasanga, Ella | |
| dc.date.accessioned | 2019-08-22T20:08:22Z | |
| dc.date.available | 2019-08-22T20:08:22Z | |
| dc.date.issued | 2018-03-14 | |
| dc.date.submitted | 2018-02-21T14:42:51-08:00 | |
| dc.description.abstract | Purpose: The beta-lactam antibiotic, ceftriaxone, attenuates tyrosine hydroxylase (TH) loss in striatum in rodent Parkinson’s disease (PD) models when given early after nigrostriatal lesion. This protection may be related to the well-known properties of ceftriaxone to increase expression of the glutamate transporter, GLT-1, which increases glutamate uptake. Ser19 TH phosphorylation, which is modulated by glutamate and Ca2+-influx, increases in proportion to TH loss following nigrostriatal lesion and may predispose TH to premature degradation via the ubiquitin-proteasome pathway. Here we evaluated if ceftriaxone could partially restore striatal TH loss, concomitant with a decrease in motor impairment, when administered 1 week after lesion induction. Methods: The ability of ceftriaxone to decrease motor impairment was evaluated after evidence of motor impairment by evaluation of forepaw adjustment steps (FAS) and open-field locomotor activity. Ceftriaxone (200 mg/kg, i.p.) was given intermittently on days 7-13, 21-27, and 35-38 post-lesion. Motor function 7 days after lesion induction was used as a baseline to evaluate if ceftriaxone could reduce motor impairment out to 40 days post-lesion. Results: There was a significant increase in FAS taken, with an overall 45% increase in mean FAS post-lesion compared to the day 7 baseline. Locomotor activity (ambulatory count and total distance) increased at the end of the study (38 days post-lesion) against the day 7 baseline following ceftriaxone. [greater than] 90% striatal TH protein loss was evident regardless of whether the rats received ceftriaxone or saline injection. However, in the substantia nigra, there was a significant increase in TH expression in the side contralateral to lesion in the ceftriaxone group. Conclusion: Taken together, these results suggest that ceftriaxone-mediated protection against locomotor decline, after the establishment of a nigrostriatal lesion, may be independent of any preservation or possible restoration of striatal TH. | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12503/27888 | |
| dc.language.iso | en | |
| dc.provenance.legacyDownloads | 0 | |
| dc.title | Evidence for improved motor function by ceftriaxone despite striatal tyrosine hydroxylase loss following nigrostriatal lesion | |
| dc.type | poster | |
| dc.type.material | text |