Pregestational Exposure to <i>T. gondii</i> Produces Maternal Antibodies That Recognize Fetal Brain Mimotopes and Induces Neurochemical and Behavioral Dysfunction in the Offspring
Eunice Romero Núñez,
Tonali Blanco Ayala,
Gustavo Ignacio Vázquez Cervantes,
Gabriel Roldán-Roldán,
Dinora Fabiola González Esquivel,
Saé Muñiz-Hernández,
Alelí Salazar,
Maricela Méndez Armenta,
Saúl Gómez-Manzo,
Hugo González-Conchillos,
Angélica Luna-Nophal,
Alma Patrica Acosta Ramírez,
Benjamín Pineda,
Anabel Jiménez-Anguiano,
Verónica Pérez de la Cruz
Affiliations
Eunice Romero Núñez
Posgrado en Ciencias Biológicas y de la Salud, DCBS, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de Mexico 09340, Mexico
Tonali Blanco Ayala
Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, Mexico
Gustavo Ignacio Vázquez Cervantes
Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, Mexico
Gabriel Roldán-Roldán
Department of Physiology, Faculty of Medicine, National Autonomous University of México, Mexico City 04510, Mexico
Dinora Fabiola González Esquivel
Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, Mexico
Saé Muñiz-Hernández
Laboratorio de Oncología Experimental, Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Secretaria de Salud, Ciudad de México 14080, Mexico
Alelí Salazar
Neuroimmunology Department, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, Mexico
Maricela Méndez Armenta
Experimental Neuropathology Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, Mexico
Saúl Gómez-Manzo
Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, México City 04530, Mexico
Hugo González-Conchillos
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (Cinvestav), México City 07360, Mexico
Angélica Luna-Nophal
Posgrado en Ciencias Biológicas y de la Salud, DCBS, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de Mexico 09340, Mexico
Alma Patrica Acosta Ramírez
Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, Mexico
Benjamín Pineda
Neuroimmunology Department, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, Mexico
Anabel Jiménez-Anguiano
Neurosciences Area, Biology of the Reproduction Department, Universidad Autónoma Metropolitana, Ciudad de México 09340, Mexico
Verónica Pérez de la Cruz
Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, Mexico
The activation of the maternal immune system by a prenatal infection is considered a risk factor for developing psychiatric disorders in the offspring. Toxoplasma gondii is one of the pathogenic infections associated with schizophrenia. Recent studies have shown an association between high levels of IgG anti-T. gondii from mothers and their neonates, with a higher risk of developing schizophrenia. The absence of the parasite and the levels of IgGs found in the early stages of life suggest a transplacental transfer of the anti-T. gondii IgG antibodies, which could bind fetal brain structures by molecular mimicry and induce alterations in neurodevelopment. This study aimed to determine the maternal pathogenic antibodies formation that led to behavioral impairment on the progeny of rats immunized with T. gondii. Female rats were immunized prior to gestation with T. gondii lysate (3 times/once per week). The anti-T. gondii IgG levels were determined in the serum of pregestational exposed females’ previous mating. After this, locomotor activity, cognitive and social tests were performed. Cortical neurotransmitter levels for dopamine and glutamate were evaluated at 60 PND in the progeny of rats immunized before gestation (Pregestational group). The maternal pathogenic antibodies were evidenced by their binding to fetal brain mimotopes in the Pregestational group and the reactivity of the serum containing anti-T. gondii IgG was tested in control fetal brains (non-immunized). These results showed that the Pregestational group presented impairment in short and long-term memory, hypoactivity and alteration in social behavior, which was also associated with a decrease in cortical glutamate and dopamine levels. We also found the IgG antibodies bound to brain mimotopes in fetuses from females immunized with T. gondii, as well as observing a strong reactivity of the serum females immunized for fetal brain structures of fetuses from unimmunized mothers. Our results suggest that the exposure to T. gondii before gestation produced maternal pathogenic antibodies that can recognize fetal brain mimotopes and lead to neurochemical and behavioral alterations in the offspring.
