期刊
NEUROBIOLOGY OF DISEASE
卷 110, 期 -, 页码 37-46出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2017.10.015
关键词
Dopamine; Striatum; Mouse; Long-term depression; Parkinson's disease; L-DOPA
资金
- Swedish Research Council [2015-02886]
- Parkinson Foundation in Sweden
- Swedish Brain Foundation
- Compagnia di San Paolo [2013 0942]
- Fondazione Cariplo
- Fondazione Istituto Italiano di Tecnologia
- Swedish Research Council [2015-02886] Funding Source: Swedish Research Council
The cJun N-terminal kinase (JNK) signaling pathway has been extensively studied with regard to its involvement in neurodegenerative processes, but little is known about its functions in neurotransmission. In a mouse model of Parkinson's disease (PD), we show that the pharmacological activation of dopamine D1 receptors (D1R) produces a large increase in JNK phosphorylation. This effect is secondary to dopamine depletion, and is restricted to the striatal projection neurons that innervate directly the output structures of the basal ganglia (dSPN). Activation of JNK in dSPN relies on cAMP-induced phosphorylation of the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), but does not require N-methyl-D-aspartate (NMDA) receptor transmission. Electrophysiological experiments on acute brain slices from PD mice show that inhibition of JNK signaling in dSPN prevents the increase in synaptic strength caused by activation of D1Rs. Together, our findings show that dopamine depletion confers to JNK the ability to mediate dopamine transmission, informing the future development of therapies for PD.
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