Ítalo Leite Figueiredo1, Priscila B Frota1, Davi G da Cunha1, Ramon da Silva Raposo2, Kildere M Canuto1, Geanne M de Andrade3, Nuno Sousa4, Sean R Moore5, Gregory M Anstead6, Jacqueline I Alvarez-Leite7, Richard L Guerrant8, Reinaldo B Oriá9. 1. Laboratory of the Biology of Tissue Healing, Ontogeny and Nutrition, Department of Morphology and Institute of Biomedicine, School of Medicine, Federal University of Ceara, Ceara, Brazil. 2. Experimental Biology Core, Health Center, University of Fortaleza, Ceara, Brazil. 3. Department of Physiology and Pharmacology and Institute of Biomedicine, School of Medicine, Federal University of Ceara, Ceara, Brazil. 4. Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. 5. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. 6. South Texas Veterans Hospital, San Antonio, TX, USA. 7. Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Minas Gerais, Brazil. 8. Center for Global Health, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA. 9. Laboratory of the Biology of Tissue Healing, Ontogeny and Nutrition, Department of Morphology and Institute of Biomedicine, School of Medicine, Federal University of Ceara, Ceara, Brazil. Electronic address: rbo5u@virginia.edu.
Abstract
OBJECTIVE: Prolonged maternal separation (PMS) in the first 2 wk of life has been associated with poor growth with lasting effects in brain structure and function. This study aimed to investigate whether PMS-induced undernutrition could cause systemic inflammation and changes in nutrition-related hormonal levels, affecting hippocampal structure and neurotransmission in C57BL/6J suckling mice. METHODS: This study assessed mouse growth parameters coupled with insulin-like growth factor-1 (IGF-1) serum levels. In addition, leptin, adiponectin, and corticosterone serum levels were measured following PMS. Hippocampal stereology and the amino acid levels were also assessed. Furthermore, we measured myelin basic protein and synapthophysin (SYN) expression in the overall brain tissue and hippocampal SYN immunolabeling. For behavioral tests, we analyzed the ontogeny of selected neonatal reflexes. PMS was induced by separating half the pups in each litter from their lactating dams for defined periods each day (4 h on day 1, 8 h on day 2, and 12 h thereafter). A total of 67 suckling pups were used in this study. RESULTS: PMS induced significant slowdown in weight gain and growth impairment. Significant reductions in serum leptin and IGF-1 levels were found following PMS. Total CA3 area and volume were reduced, specifically affecting the pyramidal layer in PMS mice. CA1 pyramidal layer area was also reduced. Overall hippocampal SYN immunolabeling was lower, especially in CA3 field and dentate gyrus. Furthermore, PMS reduced hippocampal aspartate, glutamate, and gamma-aminobutyric acid levels, as compared with unseparated controls. CONCLUSION: These findings suggest that PMS causes significant growth deficits and alterations in hippocampal morphology and neurotransmission.
OBJECTIVE: Prolonged maternal separation (PMS) in the first 2 wk of life has been associated with poor growth with lasting effects in brain structure and function. This study aimed to investigate whether PMS-induced undernutrition could cause systemic inflammation and changes in nutrition-related hormonal levels, affecting hippocampal structure and neurotransmission in C57BL/6J suckling mice. METHODS: This study assessed mouse growth parameters coupled with insulin-like growth factor-1 (IGF-1) serum levels. In addition, leptin, adiponectin, and corticosterone serum levels were measured following PMS. Hippocampal stereology and the amino acid levels were also assessed. Furthermore, we measured myelin basic protein and synapthophysin (SYN) expression in the overall brain tissue and hippocampal SYN immunolabeling. For behavioral tests, we analyzed the ontogeny of selected neonatal reflexes. PMS was induced by separating half the pups in each litter from their lactating dams for defined periods each day (4 h on day 1, 8 h on day 2, and 12 h thereafter). A total of 67 suckling pups were used in this study. RESULTS:PMS induced significant slowdown in weight gain and growth impairment. Significant reductions in serum leptin and IGF-1 levels were found following PMS. Total CA3 area and volume were reduced, specifically affecting the pyramidal layer in PMSmice. CA1 pyramidal layer area was also reduced. Overall hippocampal SYN immunolabeling was lower, especially in CA3 field and dentate gyrus. Furthermore, PMS reduced hippocampal aspartate, glutamate, and gamma-aminobutyric acid levels, as compared with unseparated controls. CONCLUSION: These findings suggest that PMS causes significant growth deficits and alterations in hippocampal morphology and neurotransmission.
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