Artículo
The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior
Autor/es | Suárez Pereira, Irene
García Domínguez, Irene Bravo, L. Santiago Pavón, Martiniano García Revilla, Juan Espinosa Oliva, Ana María Alonso Bellido, Isabel María López Martín, César Pérez Villegas, Eva María Armengol, J. A. Berrocoso, E. Venero Recio, José Luis Martínez de Pablos, Rocío Ruiz Laza, Rocío |
Departamento | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
Fecha de publicación | 2022 |
Fecha de depósito | 2022-05-16 |
Publicado en |
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Resumen | In the last decade, new non-apoptotic roles have been ascribed to apoptotic caspases. This family of proteins plays an important role in the sculpting of the brain in the early stages of development by eliminating excessive ... In the last decade, new non-apoptotic roles have been ascribed to apoptotic caspases. This family of proteins plays an important role in the sculpting of the brain in the early stages of development by eliminating excessive and nonfunctional synapses and extra cells. Consequently, impairments in this process can underlie many neurological and mental illnesses. This view is particularly relevant to dopamine because it plays a pleiotropic role in motor control, motivation, and reward processing. In this study, we analyze the effects of the elimination of caspase-8 (CASP8) on the development of catecholaminergic neurons using neurochemical, ultrastructural, and behavioral tests. To do this, we selectively delete the CASP8 gene in cells that express tyrosine hydroxylase with the help of recombination through the Cre-loxP system. Our results show that the number of dopaminergic neurons increases in the substantia nigra. In the striatum, the basal extracellular level of dopamine and potassium-evoked dopamine release decreased significantly in mice lacking CASP8, clearly showing the low dopamine functioning in tissues innervated by this neurotransmitter. This view is supported by electron microscopy analysis of striatal synapses. Interestingly, behavioral analysis demonstrates that mice lacking CASP8 show changes reminiscent of autism spectrum disorders (ASD). Our research reactivates the possible role of dopamine transmission in the pathogenesis of ASD and provides a mild model of autism. |
Agencias financiadoras | Ministerio de Economía y Competitividad (MINECO). España Junta de Andalucía Instituto de Salud Carlos III European Union (UE) |
Identificador del proyecto | RTI2018-098645-B-I00
PID2019-109569GB-I00 RTI2018-099778-B-I00 P18-RT-1372 US-1264806 PI-0080-2017 PI-0009-2017 PI-0134-2018 PEMP-0008-2020 P20_00958 CTS-510 PI18/01691 LI19/06IN-CO22 IN-C09 955684 |
Cita | Suárez Pereira, I., García Domínguez, I., Bravo, L., Santiago Pavón, M., García Revilla, J., Espinosa Oliva, A.M.,...,Ruiz Laza, R. (2022). The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior. Frontiers in Cell and Developmental Biology, 10, 839715. |
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The Absence of Caspase-8.pdf | 4.071Mb | [PDF] | Ver/ | |