中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (2): 241-243.doi: 10.4103/1673-5374.226388

• 观点:退行性病与再生 • 上一篇    下一篇

腺苷A2A-多巴胺D2受体异构体运行功能:对帕金森病药物治疗的影响

  

  • 收稿日期:2018-02-03 出版日期:2018-02-15 发布日期:2018-02-15

Adenosine A2A-dopamine D2 receptor heteromers operate striatal function: impact on Parkinson’s disease pharmacotherapeutics

Víctor Fernández-Dueñas1, 2, Sergi Ferré3, Francisco Ciruela1, 2   

  1. 1 Unitat de Farmacologia, DepartamentPatologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL, Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain;
    2 Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain;
    3 Integrative Neurobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA
  • Received:2018-02-03 Online:2018-02-15 Published:2018-02-15
  • Contact: Francisco Ciruela, fciruela@ub.edu.
  • Supported by:

    This work was supported by MINECO/ISC III (SAF2014-55700-P and PIE14/00034), IWT (SBO-140028) and Fundació la Marató de TV3 (Grant 20152031) to FC. Also, FC and VFD belong to the “Neuropharmacology and Pain” accredited research group (Generalitat de Catalunya,2014 SGR1251), and by the intramural funds of the National Institute on Drug Abuse to SF.

摘要:

orcid: 0000-0003-0832-3739 (Francisco Ciruela)

Abstract:

The basal ganglia (BG) assemble a series of deep gray matter structures forming recurrent loops that include the cortex and thalamus, and that participate in the regulation of a plethora of brain functions, including elicitation and learning of reward-and aversive stimuli-associated behaviors,motor activity control and sensorimotor gating (Bromberg-Martin et al., 2010). The striatum is the main input BG structure, thus it receives cortical glutamatergic projections from widespread areas of cortex and projects into other BG nuclei, including globus pallidus pars externa and the BG outputsglobus pallidus pars interna and substantia nigra pars reticulata. On the other hand, the substantia nigra pars compacta-ventral tegmental area (SNpc-VTA) modulates cortical-BG-thalamic circuits by means of dopaminergic innervation of the striatum. Interestingly, the main population of striatal neurons, the medium spiny neurons (MSNs),provide the origin of two different striatal efferent pathways,the direct and indirect pathways (Schiffmann et al., 2007).Both project to the BG outputs, and the direct pathway also projects to brainstem, to the SNpc-VTA. The MSN originating these two pathways are characterized by the differential expression of several key genes. Thus, while MSNs from the direct pathway (direct MSNs) express dopamine D1 receptors (D1R) and contain the neuropeptides dynorphin and substance P, indirect MSNs express dopamine D2 receptors (D2R) and contain the neuropeptide enkephalin (Fuxe et al.,2007; Schiffmann et al., 2007). Striatal dopamine from SNpc-VTA projections potentiates direct and inhibits indirect pathway MSN, which leads to a net inhibition of thalamocortical areas.