Dopamine D1 and Glutamate Receptors Co-operate With Brain-Derived Neurotrophic Factor (BDNF) and TrkB to Modulate ERK Signaling in Adult Striatal Slices.
Dopamine D1 and Glutamate Receptors Co-operate With Brain-Derived Neurotrophic Factor (BDNF) and TrkB to Modulate ERK Signaling in Adult Striatal Slices.
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DOI：
10.3389/fncel.2020.564106
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发表时间：
2020
影响因子：
5.3
通讯作者：
Brambilla R
中科院分区：
文献类型：
--
作者：
Morella I;Hallum H;Brambilla R
在纹状体中，基底神经节的输入核，细胞外信号调节激酶（ERK）通路，各种形式的行为可塑性所必需的，是由多巴胺D1和离子型谷氨酸受体的联合参与触发。在这项研究中，我们研究了潜在的串扰之间的多巴胺能，多巴胺能和脑源性神经营养因子（BDNF）-TrkB输入ERK级联使用离体模型的小鼠纹状体切片。我们的研究结果证实，伴随刺激D1和谷氨酸受体是必要的激活ERK在纹状体中型棘神经元（MSNs）。此外，我们发现当BDNF与谷氨酸或D1激动剂SKF 38393共同应用时，ERK激活显著增强，支持BDNF，谷氨酸和D1 R介导的信号之间可能整合的想法。有趣的是，通过BDNF-TrkB的ERK激活在AMPAR/NMDAR或D1受体阻断后上调，表明这两种神经递质系统对BDNF介导的信号传导的负调节作用。然而，观察到的ERK 1/2磷酸化的增强并不导致相应的下游信号在核水平上的变化。相反，Trk B拮抗剂cyclotraxin B部分阻止谷氨酸和D1介导的ERK激活。总之，这些结果表明，多巴胺能，多巴胺能和BDNF受体系统之间的复杂和意想不到的相互作用，以调节纹状体神经元的ERK通路。
In the striatum, the input nucleus of the basal ganglia, the extracellular-signal-regulated kinase (ERK) pathway, necessary for various forms of behavioral plasticity, is triggered by the combined engagement of dopamine D1 and ionotropic glutamate receptors. In this study, we investigated the potential crosstalk between glutamatergic, dopaminergic, and brain-derived neurotrophic factor (BDNF)-TrkB inputs to ERK cascade by using an ex vivo model of mouse striatal slices. Our results confirmed that the concomitant stimulation of D1 and glutamate receptors is necessary to activate ERK in striatal medium spiny neurons (MSNs). Moreover, we found that ERK activation is significantly enhanced when BDNF is co-applied either with glutamate or the D1 agonist SKF38393, supporting the idea of possible integration between BDNF, glutamate, and D1R-mediated signaling. Interestingly, ERK activation via BDNF-TrkB is upregulated upon blockade of either AMPAR/NMDAR or D1 receptors, suggesting a negative regulatory action of these two neurotransmitter systems on BDNF-mediated signaling. However, the observed enhancement of ERK1/2 phosphorylation does not result in corresponding downstream signaling changes at the nuclear level. Conversely, the TrkB antagonist cyclotraxin B partially prevents glutamate- and D1-mediated ERK activation. Altogether, these results suggest a complex and unexpected interaction among dopaminergic, glutamatergic, and BDNF receptor systems to modulate the ERK pathway in striatal neurons.
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影响因子：
5.3
作者：
Bernardi, Rick F.;Olevska, Anastasia;Spanagel, Rainer
通讯作者：
Spanagel, Rainer
影响因子：
5.3
作者：
Baydyuk M;Xu B
通讯作者：
Xu B
DOI：
10.1126/science.1222265
发表时间：
2012-10-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Koo JW;Mazei-Robison MS;Chaudhury D;Juarez B;LaPlant Q;Ferguson D;Feng J;Sun H;Scobie KN;Damez-Werno D;Crumiller M;Ohnishi YN;Ohnishi YH;Mouzon E;Dietz DM;Lobo MK;Neve RL;Russo SJ;Han MH;Nestler EJ
通讯作者：
Nestler EJ
影响因子：
10.6
作者：
Fasano S;D'Antoni A;Orban PC;Valjent E;Putignano E;Vara H;Pizzorusso T;Giustetto M;Yoon B;Soloway P;Maldonado R;Caboche J;Brambilla R
通讯作者：
Brambilla R
影响因子：
3.7
作者：
Li C;Dabrowska J;Hazra R;Rainnie DG
通讯作者：
Rainnie DG