RT Journal Article
T1 The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior
T2 La ausencia de caspasa-8 en el sistema dopaminérgico provoca un comportamiento leve similar al autismo
A1 Suárez-Pereira, Irene.
A1 García-Domínguez, Irene.
A1 Bravo, Lidia.
A1 Santiago, Martí.
A1 García-Revilla, Juan.
A1 Espinosa-Oliva, A. M.
A1 Alonso-Bellido, I.A.
A1 López-Martín, C.
A1 Pérez-Villegas, E.
A1 Armengol Butrón de Mújica, José Ángel
A1 Berrocoso, Esther.
A1 Venero, JL.
A1 de Pablos, RM.
A1 Ruiz, R.
K1 Autism spectrum disorder
K1 Dopaminergic system
K1 Caspase 8
K1 Electron microscopy
K1 Synapsis
K1 Behavioral test
AB 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.
PB Frontiers Media S.A.
YR 2022
FD 2022-04-05
LK https://hdl.handle.net/10433/25717
UL https://hdl.handle.net/10433/25717
LA en
NO Front. Cell Dev. Biol. 10:839715.
NO Departamento fisiología, anatomía y biología celular
DS RIO
RD May 8, 2026