PT320, a Sustained-Release GLP-1 Receptor Agonist, Ameliorates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease.
PT320, a Sustained-Release GLP-1 Receptor Agonist, Ameliorates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease.
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DOI：
10.3390/ijms24054687
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发表时间：
2023-02-28
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
确定PT 320对进行性帕金森病（PD）MitoPark小鼠模型中L-DOPA诱导的运动障碍行为和神经化学的疗效。为了研究PT 320对L-DOPA致敏小鼠中运动障碍表现的影响，从5或17周龄小鼠开始施用临床上可转化的每两周一次的PT 320剂量。早期治疗组从20周龄开始给予左旋多巴，并进行纵向评估，直至22周。晚期治疗组从28周龄开始给予左旋多巴，并纵向观察至29周龄。为了探索多巴胺能传递，利用快速扫描循环伏安法（FSCV）来测量药物处理后纹状体切片中突触前多巴胺（DA）的动态。PT 320的早期给药显著减轻了L-DOPA诱导的异常不自主运动的严重程度; PT 320特别改善了过多的站立次数以及异常的爪运动，而它不影响L-DOPA诱导的运动过度活跃。相比之下，PT 320的晚期给药没有减弱任何L-DOPA诱导的运动障碍测量。此外，用PT 320的早期治疗显示出不仅增加L-DOPA未处理的MitoPark小鼠的纹状体切片中DA的紧张性和阶段性释放，而且增加L-DOPA致敏的动物中的DA的紧张性和阶段性释放。在MitoPark小鼠中，PT 320的早期治疗改善了L-DOPA诱导的运动障碍，这可能与PD中DA去神经支配的进行性水平有关。
To determine the efficacy of PT320 on L-DOPA-induced dyskinetic behaviors, and neurochemistry in a progressive Parkinson’s disease (PD) MitoPark mouse model. To investigate the effects of PT320 on the manifestation of dyskinesia in L-DOPA-primed mice, a clinically translatable biweekly PT320 dose was administered starting at either 5 or 17-weeks-old mice. The early treatment group was given L-DOPA starting at 20 weeks of age and longitudinally evaluated up to 22 weeks. The late treatment group was given L-DOPA starting at 28 weeks of age and longitudinally observed up to 29 weeks. To explore dopaminergic transmission, fast scan cyclic voltammetry (FSCV) was utilized to measure presynaptic dopamine (DA) dynamics in striatal slices following drug treatments. Early administration of PT320 significantly mitigated the severity L-DOPA-induced abnormal involuntary movements; PT320 particularly improved excessive numbers of standing as well as abnormal paw movements, while it did not affect L-DOPA-induced locomotor hyperactivity. In contrast, late administration of PT320 did not attenuate any L-DOPA-induced dyskinesia measurements. Moreover, early treatment with PT320 was shown to not only increase tonic and phasic release of DA in striatal slices in L-DOPA-naïve MitoPark mice, but also in L-DOPA-primed animals. Early treatment with PT320 ameliorated L-DOPA-induced dyskinesia in MitoPark mice, which may be related to the progressive level of DA denervation in PD.
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影响因子：
4.8
作者：
Chen, Yuan-Hao;Harvey, Brandon K.;Lupica, Carl R.
通讯作者：
Lupica, Carl R.
DOI：
10.1016/s0140-6736(17)31585-4
发表时间：
2017-10-07
期刊：
Lancet (London, England)
影响因子：
--
作者：
Athauda D;Maclagan K;Skene SS;Bajwa-Joseph M;Letchford D;Chowdhury K;Hibbert S;Budnik N;Zampedri L;Dickson J;Li Y;Aviles-Olmos I;Warner TT;Limousin P;Lees AJ;Greig NH;Tebbs S;Foltynie T
通讯作者：
Foltynie T
影响因子：
3
作者：
KAWAGOE, KT;ZIMMERMAN, JB;WIGHTMAN, RM
通讯作者：
WIGHTMAN, RM
影响因子：
8.6
作者：
Kumar, N;Van Gerpen, JA;Ahlskog, JE
通讯作者：
Ahlskog, JE
影响因子：
--
作者：
Jankovic, J;Rajput, AH;Perl, DP
通讯作者：
Perl, DP