RT Journal Article
T1 The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior
A1 Suarez-Pereira, I.
A1 Garcia-Dominguez, I.
A1 Bravo, L.
A1 Santiago, M.
A1 Garcia-Revilla, J.
A1 Espinosa-Oliva, A. M.
A1 Alonso-Bellido, I. M.
A1 Lopez-Martin, C.
A1 Perez-Villegas, E. M.
A1 Armengol, J. A.
A1 Berrocoso, E.
A1 Venero, J. L.
A1 de Pablos, R. M.
A1 Ruiz, R.
K1 Autism spectrum disorder
K1 Dopaminergic system
K1 Caspase 8
K1 Electron microscopy
K1 Synapsis
K1 Behavioral test
K1 Cell-death
K1 Spectrum disorders
K1 Substantia-nigra
K1 Apoptosis
K1 Modulation
K1 Expression
K1 Induction
K1 Necroptosis
K1 Receptors
K1 Cytokines
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 Research Foundation
SN 2296-634X
YR 2022
FD 2022-04-05
LK http://hdl.handle.net/10668/20531
UL http://hdl.handle.net/10668/20531
LA en
NO Suárez-Pereira I, García-Domínguez I, Bravo L, Santiago M, García-Revilla J, Espinosa-Oliva AM, et al. The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior. Front Cell Dev Biol. 2022 Apr 5;10:839715. doi: 10.3389/fcell.2022.839715. Erratum in: Front Cell Dev Biol. 2022 Sep 28;10:1040623
DS RISalud
RD Apr 6, 2025