| Autor: |
Amaro A; Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal., Sousa D; Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal., Sá-Rocha M; Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal., Ferreira-Junior MD; Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.; Department of Physiological Sciences, Institute of Biological Sciences, University Federal of Goiás, Goiânia 74690-900, Brazil., Rosendo-Silva D; Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal., Saavedra LPJ; Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringa, Maringa 87020-900, Brazil., Barra C; Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal.; Internal Medicine Department, University Hospital Center of Coimbra, 3004-561 Coimbra, Portugal., Monteiro-Alfredo T; Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal., Gomes RM; Department of Physiological Sciences, Institute of Biological Sciences, University Federal of Goiás, Goiânia 74690-900, Brazil., de Freitas Mathias PC; Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringa, Maringa 87020-900, Brazil., Baptista FI; Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal., Matafome P; Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal.; Coimbra Health School (EsTeSC), Polytechnic University of Coimbra, 3046-854 Coimbra, Portugal. |
| Abstrakt: |
Nutritional disturbances during the early postnatal period can have long-lasting effects on neurodevelopment and may be related to behavioural changes at adulthood. While such neuronal connection disruption can contribute to social and behaviour alterations, the dysregulation of the neuroendocrine pathways involved in nutrient-sensing balance may also cause such impairments, although the underlying mechanisms are still unclear. We aimed to evaluate sex-specific neurodevelopmental and behavioural changes upon postnatal overfeeding and determine the potential underpinning mechanisms at the central nervous system level, with a focus on the interconnection between synaptic and neuroendocrine molecular alterations. At postnatal day 3 (PND3) litters were culled to three animals (small litter procedure). Neurodevelopmental tests were conducted at infancy, whereas behavioural tests to assess locomotion, anxiety, and memory were performed at adolescence, together with molecular analysis of the hippocampus, hypothalamus, and prefrontal cortex. At infancy, females presented impaired acquisition of an auditory response, eye opening, olfactory discrimination, and vestibular system development, suggesting that female offspring neurodevelopment/maturation was deeply affected. Male offspring presented a transitory delay in locomotor performance., while both offspring had lower upper limb strength. At adolescence, both sexes presented anxious-like behaviour without alterations in short-term memory retention. Both males and females presented lower NPY1R levels in a region-specific manner. Furthermore, both sexes presented synaptic changes in the hippocampus (lower GABA A in females and higher GABA A levels in males), while, in the prefrontal cortex, similar higher GABA A receptor levels were observed. At the hypothalamus, females presented synaptic changes, namely higher vGLUT1 and PSD95 levels. Thus, we demonstrate that postnatal overfeeding modulates offspring behaviour and dysregulates nutrient-sensing mechanisms such as NPY and GABA in a sex- and brain-region-specific manner. |
