L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease.
L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease.
复制标题
DOI：
10.3390/ijms222212346
复制
发表时间：
2021-11-16
影响因子：
5.6
通讯作者：
Lane EL
中科院分区：
文献类型：
--
作者：
Elabi OF;Davies JS;Lane EL
细胞疗法是治疗帕金森氏病(PD)的一种有前途的治疗方法，然而到目前为止的临床试验表明，患者的存活率相对较低，患者之间的差异显著。胰升糖素样肽-1受体(GLP-1R)激动剂对内源性多巴胺能神经元具有潜在的神经保护作用。这项研究探索这些药物是否可以类似地支持新移植的神经元的生长和存活。6-羟基多巴胺损毁的SD大鼠接受胚胎第14天Wistar大鼠胚胎中脑多巴胺能腹侧中脑细胞纹状体内移植。然后，移植大鼠在细胞移植前和细胞移植后每隔48h给予生理盐水或L-多巴(12 mg/kg)。细胞移植后立即给予外周GLP-1R激动剂(exendin-4，0.5μg/kg，每日两次或利拉鲁肽，100μg/kg，每日一次)，并在整个研究过程中保持不变。给予exendin-4后移植物存活率增加，同时使用exendin-4和利拉鲁肽治疗后运动功能显著改善。然而，在服用L-多巴的大鼠中没有观察到这种作用。相比之下，使用利拉鲁肽的L-多巴治疗增加了移植物的体积，同时也增加了运动功能。然而，这种改善伴随着移植物周围白细胞浸润的增加。联合使用L-多巴和埃森丁-4还导致了利拉鲁肽未见的胰岛素抵抗指标，这可能支持了两种Glp1-R激动剂之间的不同效果。总体而言，对移植患者补充GLP-1R激动剂可能有一些好处，但需要更深入地考虑与其他药物治疗的潜在相互作用。
Cell therapy is a promising treatment for Parkinson’s disease (PD), however clinical trials to date have shown relatively low survival and significant patient-to-patient variability. Glucagon Like Peptide-1 receptor (GLP-1R) agonists have potential neuroprotective effects on endogenous dopaminergic neurons. This study explores whether these agents could similarly support the growth and survival of newly transplanted neurons. 6-OHDA lesioned Sprague Dawley rats received intra-striatal grafts of dopaminergic ventral mesencephalic cells from embryonic day 14 Wistar rat embryos. Transplanted rats then received either saline or L-dopa (12 mg/kg) administered every 48 h prior to, and following cell transplantation. Peripheral GLP-1R agonist administration (exendin-4, 0.5 μg/kg twice daily or liraglutide, 100 μg/kg once daily) commenced immediately after cell transplantation and was maintained throughout the study. Graft survival increased under administration of exendin-4, with motor function improving significantly following treatment with both exendin-4 and liraglutide. However, this effect was not observed in rats administered with L-dopa. In contrast, L-dopa treatment with liraglutide increased graft volume, with parallel increases in motor function. However, this improvement was accompanied by an increase in leukocyte infiltration around the graft. The co-administration of L-dopa and exendin-4 also led to indicators of insulin resistance not seen with liraglutide, which may underpin the differential effects observed between the two GLP1-R agonists. Overall, there may be some benefit to the supplementation of grafted patients with GLP-1R agonists but the potential interaction with other pharmacological treatments needs to be considered in more depth.
登录
查看更多内容
影响因子：
3.7
作者：
Brabazon F;Bermudez S;Shaughness M;Khayrullina G;Byrnes KR
通讯作者：
Byrnes KR
影响因子：
9.3
作者：
Elabi OF;Cunha JPMCM;Gaceb A;Fex M;Paul G
通讯作者：
Paul G
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：
6.1
作者：
Breger, Ludivine S.;Dunnett, Stephen B.;Lane, Emma L.
通讯作者：
Lane, Emma L.
影响因子：
158.5
作者：
GUTNIAK, M;ORSKOV, C;EFENDIC, S
通讯作者：
EFENDIC, S