MCP-1 Signaling Disrupts Social Behavior by Modulating Brain Volumetric Changes and Microglia Morphology
Por:
Maldonado-Ruiz, Roger, Trujillo-Villarreal, Luis A., Montalvo-Martinez, Larisa, Fabian Mercado-Gomez, Octavio, Arriaga-Avila, Virginia, Garza-Ocanas, Lourdes, Ortiz-Lopez, Rocio, Garza-Villarreal, Eduardo A., Guevara-Guzman, Rosalinda, Camacho-Morales, Alberto
Publicada:
1 feb 2022
Ahead of Print:
1 nov 2021
Resumen:
Autism spectrum disorder (ASD) is a disease characterized by reduced
social interaction and stereotypic behaviors and related to macroscopic
volumetric changes in cerebellar and somatosensory cortices (SPP).
Epidemiological and preclinical models have confirmed that a
proinflammatory profile during fetal development increases ASD
susceptibility after birth. Here, we aimed to globally identify the
effect of maternal exposure to high-energy dense diets, which we refer
to as cafeteria diet (CAF) on peripheral and central proinflammatory
profiles, microglia reactivity, and volumetric brain changes related to
assisting defective social interaction in the mice offspring. We found a
sex-dependent effect of maternal exposure to CAF diet or inoculation of
the dsARN mimetic Poly (I:C) on peripheral proinflammatory and social
interaction in the offspring. Notably, maternal exposure to CAF diet
impairs social interaction and favors an increase in anxiety in male but
not female offspring. Also, CAF diet exposure or Poly (I:C) inoculation
during fetal programming promote peripheral proinflammatory profile in
the ASD-diagnosed male but not in females. Selectively, we found a
robust accumulation of the monocyte chemoattractant protein-1 (MCP-1) in
plasma of ASD-diagnosed males exposed to CAF during fetal development.
Biological assessment of MCP-1 signaling in brain confirms that systemic
injection of MCP-1-neutralizing antibody reestablished social
interaction and blocked anxiety, accompanied by a reduction in
cerebellar lobule X (CbX) volume and an increase volume of the primary
somatosensory (SSP) cortex in male offspring. These data highlight the
contribution of diet-dependent MCP-1 signaling on volumetric brain
changes and microglia morphology promoting ASD-like behavior in male
mice.
Filiaciones:
Maldonado-Ruiz, Roger:
Univ Autonoma Nuevo Leon, Coll Med, Dept Biochem, Calle Dr Eduardo Aguirre Pequeno S-N, Monterrey 64460, Nuevo Leon, Mexico
Univ Autonoma Nuevo Leon, Ctr Res & Dev Hlth Sci, Neurometab Unit, San Nicolas De Los Garza, Nuevo Leon, Mexico
Trujillo-Villarreal, Luis A.:
Univ Autonoma Nuevo Leon, Coll Med, Dept Biochem, Calle Dr Eduardo Aguirre Pequeno S-N, Monterrey 64460, Nuevo Leon, Mexico
Univ Autonoma Nuevo Leon, Ctr Res & Dev Hlth Sci, Neurometab Unit, San Nicolas De Los Garza, Nuevo Leon, Mexico
Montalvo-Martinez, Larisa:
Univ Autonoma Nuevo Leon, Coll Med, Dept Biochem, Calle Dr Eduardo Aguirre Pequeno S-N, Monterrey 64460, Nuevo Leon, Mexico
Univ Autonoma Nuevo Leon, Ctr Res & Dev Hlth Sci, Neurometab Unit, San Nicolas De Los Garza, Nuevo Leon, Mexico
Fabian Mercado-Gomez, Octavio:
Univ Nacl Autonoma Mexico, Coll Med, Dept Physiol, Mexico City, DF, Mexico
Arriaga-Avila, Virginia:
Univ Nacl Autonoma Mexico, Coll Med, Dept Physiol, Mexico City, DF, Mexico
Garza-Ocanas, Lourdes:
Univ Autonoma Nuevo Leon, Coll Med, Dept Pharmacol & Toxicol, San Nicolas De Los Garza, Nuevo Leon, Mexico
Ortiz-Lopez, Rocio:
Tecnol Monterrey, Sch Med & Hlth Sci, Monterrey, Mexico
Garza-Villarreal, Eduardo A.:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Mexico City, DF, Mexico
Guevara-Guzman, Rosalinda:
Univ Nacl Autonoma Mexico, Coll Med, Dept Physiol, Mexico City, DF, Mexico
Camacho-Morales, Alberto:
Univ Autonoma Nuevo Leon, Coll Med, Dept Biochem, Calle Dr Eduardo Aguirre Pequeno S-N, Monterrey 64460, Nuevo Leon, Mexico
Univ Autonoma Nuevo Leon, Ctr Res & Dev Hlth Sci, Neurometab Unit, San Nicolas De Los Garza, Nuevo Leon, Mexico
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