RT Journal Article
T1 Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits.
A1 Ortega-de San Luis, Clara
A1 Sanchez-Garcia, Manuel A
A1 Nieto-Gonzalez, Jose Luis
A1 García-Junco-Clemente, Pablo
A1 Montero-Sanchez, Adoracion
A1 Fernandez-Chacon, Rafael
A1 Pascual, Alberto
K1 GDNF
K1 Parkinson’s disease
K1 Shh
K1 neurotrophic support
K1 striatal interneurons
K1 substantia nigra
AB 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.
YR 2018
FD 2018-07-30
LK http://hdl.handle.net/10668/12772
UL http://hdl.handle.net/10668/12772
LA en
DS RISalud
RD Apr 5, 2025