Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/112207
Title: Postnatal Overfeeding in Rodents Induces a Neurodevelopment Delay and Anxious-like Behaviour Accompanied by Sex- and Brain-Region-Specific Synaptic and Metabolic Changes
Authors: Amaro, Andreia 
Sousa, Diana Isabel Teixeira de 
Sá-Rocha, Mariana 
Ferreira-Junior, Marcos Divino
Rosendo-Silva, Daniela 
Saavedra, Lucas Paulo Jacinto
Barra, Cátia 
Monteiro-Alfredo, Tamaeh 
Gomes, Rodrigo Mello
de Freitas Mathias, Paulo Cezar
Baptista, Filipa I. 
Matafome, Paulo 
Keywords: lactation; overfeeding; neurodevelopment; anxious-like behaviour; energy balance; synaptic balance
Issue Date: 15-Aug-2023
Publisher: MDPI
Project: UIDB//04539/2020 
UIDP//04539/2020 
LA/P/0058/2020: CIBB 
UI/BD/154406/2023 
Serial title, monograph or event: Nutrients
Volume: 15
Issue: 16
Abstract: 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 GABAA in females and higher GABAA levels in males), while, in the prefrontal cortex, similar higher GABAA 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.
URI: https://hdl.handle.net/10316/112207
ISSN: 2072-6643
DOI: 10.3390/nu15163581
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais
I&D ICBR - Artigos em Revistas Internacionais

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