Artículo
Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuits
Autor/es | Ortega de San Luís, Clara
Sánchez García, Manuel A. Nieto González, José Luis García-Junco Clemente, Pablo Montero Sánchez, Adoración Fernández-Chacón, Rafael Pascual, Alberto |
Departamento | Instituto de Biomedicina de Sevilla (IBIS) Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Fecha de publicación | 2018-06-11 |
Fecha de depósito | 2018-10-09 |
Publicado en |
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Resumen | The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), ... The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast‐spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF‐independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value. |
Agencias financiadoras | Ministerio de Economía y Competitividad (MINECO). España Junta de Andalucía |
Identificador del proyecto | SAF2012-33816
SAF2015-64111-R PIE13/00004 CTS2138 AP2010-1598 FPU13 00530 |
Cita | Ortega de San Luís, C., Sánchez García, M.A., Nieto González, J.L., García-Junco Clemente, P., Montero Sánchez, A., Fernández-Chacón, R. y Pascual, A. (2018). Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuits. Aging Cell, 17 (5), e12821-1-e12821-14. |
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