PMID- 34797523 OWN - NLM STAT- MEDLINE DCOM- 20220407 LR - 20220531 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 59 IP - 2 DP - 2022 Feb TI - MCP-1 Signaling Disrupts Social Behavior by Modulating Brain Volumetric Changes and Microglia Morphology. PG - 932-949 LID - 10.1007/s12035-021-02649-7 [doi] AB - 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. CI - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Maldonado-Ruiz, Roger AU - Maldonado-Ruiz R AD - Department of Biochemistry, College of Medicine, Universidad Autonoma de Nuevo Leon, Calle Dr. Eduardo Aguirre Pequeno s/n, Colonia Mitras Centro, 64460, Monterrey, Nuevo Leon, Mexico. AD - Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Mexico. FAU - Trujillo-Villarreal, Luis A AU - Trujillo-Villarreal LA AD - Department of Biochemistry, College of Medicine, Universidad Autonoma de Nuevo Leon, Calle Dr. Eduardo Aguirre Pequeno s/n, Colonia Mitras Centro, 64460, Monterrey, Nuevo Leon, Mexico. AD - Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Mexico. FAU - Montalvo-Martinez, Larisa AU - Montalvo-Martinez L AD - Department of Biochemistry, College of Medicine, Universidad Autonoma de Nuevo Leon, Calle Dr. Eduardo Aguirre Pequeno s/n, Colonia Mitras Centro, 64460, Monterrey, Nuevo Leon, Mexico. AD - Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Mexico. FAU - Mercado-Gomez, Octavio Fabian AU - Mercado-Gomez OF AD - Deparment of Physiology, College of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico. FAU - Arriaga-Avila, Virginia AU - Arriaga-Avila V AD - Deparment of Physiology, College of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico. FAU - Garza-Ocanas, Lourdes AU - Garza-Ocanas L AD - Department of Pharmacology and Toxicology, College of Medicine, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Mexico. FAU - Ortiz-Lopez, Rocio AU - Ortiz-Lopez R AD - Tecnologico de Monterrey, School of Medicine and Health Sciences, Monterrey, Mexico. FAU - Garza-Villarreal, Eduardo A AU - Garza-Villarreal EA AD - Universidad Nacional Autonoma de Mexico, Instituto de Neurobiologia, Mexico City, Mexico. FAU - Guevara-Guzman, Rosalinda AU - Guevara-Guzman R AD - Deparment of Physiology, College of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico. FAU - Camacho-Morales, Alberto AU - Camacho-Morales A AUID- ORCID: 0000-0002-2588-9489 AD - Department of Biochemistry, College of Medicine, Universidad Autonoma de Nuevo Leon, Calle Dr. Eduardo Aguirre Pequeno s/n, Colonia Mitras Centro, 64460, Monterrey, Nuevo Leon, Mexico. alberto.camachomr@uanl.edu.mx. AD - Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Mexico. alberto.camachomr@uanl.edu.mx. LA - eng GR - 255317/Consejo Nacional de Ciencia y Tecnologia/ GR - 708452/Consejo Nacional de Ciencia y Tecnologia/ GR - 573686/Consejo Nacional de Ciencia y Tecnologia/ GR - IBRO-LARC 2020/International Brain Research Organization/ PT - Journal Article DEP - 20211119 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Chemokine CCL2) SB - IM MH - Animals MH - *Autism Spectrum Disorder/metabolism/pathology MH - Brain/anatomy & histology/metabolism MH - *Chemokine CCL2/metabolism MH - Female MH - Male MH - Mice MH - Microglia/cytology MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Social Behavior OTO - NOTNLM OT - Autism OT - Cerebellum OT - Cytokines OT - MCP-1 OT - Magnetic resonance imaging OT - Maternal programming EDAT- 2021/11/20 06:00 MHDA- 2022/04/08 06:00 CRDT- 2021/11/19 12:21 PHST- 2021/09/13 00:00 [received] PHST- 2021/11/15 00:00 [accepted] PHST- 2021/11/20 06:00 [pubmed] PHST- 2022/04/08 06:00 [medline] PHST- 2021/11/19 12:21 [entrez] AID - 10.1007/s12035-021-02649-7 [pii] AID - 10.1007/s12035-021-02649-7 [doi] PST - ppublish SO - Mol Neurobiol. 2022 Feb;59(2):932-949. doi: 10.1007/s12035-021-02649-7. Epub 2021 Nov 19.