RT Journal Article
T1 Selective deletion of Caspase-3 gene in the dopaminergic system exhibits autistic-like behaviour
T2 La eliminación selectiva del gen Caspasa-3 en el sistema dopaminérgico produce un comportamiento similar al autista.
A1 García-Domínguez, Irene.
A1 Suárez-Pereira, Irene.
A1 Santiago Martí., 
A1 Pérez-Villegas, E.
A1 Bravo, Lidia.
A1 López-Martín, Carolina.
A1 Roca-Ceballosa, Maria Angustias.
A1 García-Revilla, Juan.
A1 Espinosa-Oliva, Ana M.
A1 Rodríguez-Gómez, José A.
A1 Bertrand, Josephe.
A1 Berrocoso, Esther.
A1 Armengol Butrón de Mújica, José Ángel
A1 Venero, José L.
A1 Ruiz, Rocio.
A1 de Pablos, Rocio M.
K1 Caspase
K1 Autisms
K1 Dopaminergic system
K1 Catecholaminergic neurons
K1 Tyrosine hydroxylase
AB Apoptotic caspases are thought to play critical roles in elimination of excessive and non-functional synapses and removal of extra cells during early developmental stages. Hence, an impairment of this process may thus constitute a basis for numerous neurological and psychiatric diseases. This view is especially relevant for dopamine due to its pleiotropic roles in motor control, motivation and reward processing. Here, we have analysed the effect of caspase-3 depletion on the development of catecholaminergic neurons and performed a wide array of neurochemical, ultrastructural and behavioural assays. To achieve this, we performed selective deletion of the Casp3 gene in tyrosine hydroxylase (TH)-expressing cells using Cre-loxP-mediated recombination. Histological evaluation of most relevant catecholaminergic nuclei revealed the ventral mesencephalon as the most affected region. Stereological analysis demonstrated an increase in the number of TH-positive neurons in both the substantia nigra and ventral tegmental area along with enlarged volume of the ventral midbrain. Analysis of main innervating tissues revealed a rather contrasting profile. In striatum, basal extracellular levels and potassiumevoked DA release were significantly reduced in mice lacking Casp3, a clear indication of dopaminergic hypofunction in dopaminergic innervating tissues. This view was sustained by analysis of TH-labelled dopaminergic terminals by confocal and electron microscopy. Remarkably, at a behavioural level, Casp3-deficient mice exhibited impaired social interaction, restrictive interests and repetitive stereotypies, which are considered the core symptoms of autism spectrum disorder (ASD). Our study revitalizes the potential involvement of dopaminergic transmission in ASD and provides an excellent model to get further insights in ASD pathogenesis.
PB Elsevier
YR 2021
FD 2021-01-10
LK https://hdl.handle.net/10433/25719
UL https://hdl.handle.net/10433/25719
LA en
NO Irene García-Domínguez, Irene Suárez-Pereira, Marti Santiago, Eva M. Pérez-Villegas, Lidia Bravo, Carolina López-Martín, María Angustias Roca-Ceballos, Juan García-Revilla, Ana M. Espinosa-Oliva, José A. Rodríguez-Gómez, Bertrand Joseph, Esther Berrocoso, José Ángel Armengol, José L. Venero, Rocío Ruiz, Rocío M. de Pablos, Selective deletion of Caspase-3 gene in the dopaminergic system exhibits autistic-like behaviour, Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 104, 2021, 110030, ISSN 0278-5846, https://doi.org/10.1016/j.pnpbp.2020.110030
NO Departamento fisiología, anatomía y biología celular
DS RIO
RD May 8, 2026