PT320, Sustained-Release Exendin-4, Mitigates L-DOPA-Induced Dyskinesia in a Rat 6-Hydroxydopamine Model of Parkinson’s Disease
| Autor: | Barry J. Hoffer, Nigel H. Greig, Yun Wang, Hee Kyung Kim, Shuchun Chen, Ho Il Choi, Yung Yung Yang, Elliot J. Glotfelty, Doo Sup Choi, Seong Jin Yu, Jin Jung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Levodopa medicine.medical_specialty Parkinson's disease exenatide lcsh:RC321-571 03 medical and health sciences 0302 clinical medicine Dopamine Internal medicine exendin-4 medicine levodopa Medial forebrain bundle lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research Hydroxydopamine Benserazide business.industry General Neuroscience medicine.disease Abnormal involuntary movement L-DOPA-induced dyskinesia 030104 developmental biology Endocrinology Dyskinesia glucagon-like peptide-1 PT302 Parkinson’s disease PT320 medicine.symptom business 030217 neurology & neurosurgery medicine.drug Neuroscience |
| Zdroj: | Frontiers in Neuroscience Frontiers in Neuroscience, Vol 14 (2020) |
| ISSN: | 1662-453X 1662-4548 |
| Popis: | Background We previously demonstrated that subcutaneous administration of PT320, a sustained-release (SR) form of exendin-4, resulted in the long-term maintenance of steady-state exenatide (exendin-4) plasma and target levels in 6-hydroxydopamine (6-OHDA)-pretreated animals. Additionally, pre- or post-treatment with PT320 mitigated the early stage of 6-OHDA-induced dopaminergic neurodegeneration. The purpose of this study was to evaluate the effect of PT320 on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced abnormal involuntary movements (AIMs) in the rat 6-OHDA model of Parkinson's disease. Methods Adult male Sprague-Dawley rats were unilaterally lesioned in the right medial forebrain bundle by 6-OHDA. L-DOPA and benserazide were given daily for 22 days, starting from 4 weeks after lesioning. PT320 was co-administered weekly for 3 weeks. AIM was evaluated on days 1, 16, and 22 after initiating L-DOPA/benserazide + PT320 treatment. Brain tissues were subsequently collected for HPLC measurements of dopamine (DA) and metabolite concentrations. Results L-DOPA/benserazide increased AIMs of limbs and axial as well as the sum of all dyskinesia scores (ALO) over 3 weeks. PT320 significantly reduced the AIM scores of limbs, orolingual, and ALO. Although PT320 did not alter DA levels in the lesioned striatum, PT320 significantly attenuated 6-OHDA-enhanced DA turnover. Conclusion PT320 attenuates L-DOPA/benserazide-induced dyskinesia in a 6-OHDA rat model of PD and warrants clinical evaluation to mitigate Parkinson's disease in humans. |
| Databáze: | OpenAIRE |
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