Adult rats sired by obese fathers present learning deficits associated with epigenetic and neurochemical alterations linked to impaired brain glutamatergic signaling.

Autor: Mezo-González CE; UMR Physiologie des Adaptations Nutritionnelles, INRAE - Nantes Université, Nantes, France., García-Santillán JA; UMR Physiologie des Adaptations Nutritionnelles, INRAE - Nantes Université, Nantes, France., Kaeffer B; UMR Physiologie des Adaptations Nutritionnelles, INRAE - Nantes Université, Nantes, France., Gourdel M; CRNH-O Mass Spectrometry Core Facility, Nantes, France.; CNRS, INSERM, L'institut du Thorax, Université de Nantes, Nantes, France.; CHU Nantes, INSERM, CNRS, SFR Santé, INSERM UMS 016, CNRS UMS 3556, Université de Nantes, Nantes, France., Croyal M; CRNH-O Mass Spectrometry Core Facility, Nantes, France.; CNRS, INSERM, L'institut du Thorax, Université de Nantes, Nantes, France.; CHU Nantes, INSERM, CNRS, SFR Santé, INSERM UMS 016, CNRS UMS 3556, Université de Nantes, Nantes, France., Bolaños-Jiménez F; UMR Physiologie des Adaptations Nutritionnelles, INRAE - Nantes Université, Nantes, France.
Jazyk: angličtina
Zdroj: Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2024 Mar; Vol. 240 (3), pp. e14090. Date of Electronic Publication: 2024 Jan 17.
DOI: 10.1111/apha.14090
Abstrakt: Aim: Offspring of obese mothers are at high risk of developing metabolic syndrome and cognitive disabilities. Impaired metabolism has also been reported in the offspring of obese fathers. However, whether brain function can also be affected by paternal obesity has barely been examined. This study aimed to characterize the learning deficits resulting from paternal obesity versus those induced by maternal obesity and to identify the underlying mechanisms.
Methods: Founder control and obese female and male Wistar rats were mated to constitute three first-generation (F1) experimental groups: control mother/control father, obese mother/control father, and obese father/control mother. All F1 animals were weaned onto standard chow and underwent a learning test at 4 months of age, after which several markers of glutamate-mediated synaptic plasticity together with the expression of miRNAs targeting glutamate receptors and the concentration of kynurenic and quinolinic acids were quantified in the hippocampus and frontal cortex.
Results: Maternal obesity induced a severe learning deficit by impairing memory encoding and memory consolidation. The offspring of obese fathers also showed reduced memory encoding but not impaired long-term memory formation. Memory deficits in offspring of obese fathers and obese mothers were associated with a down-regulation of genes encoding NMDA glutamate receptors subunits and several learning-related genes along with impaired expression of miR-296 and miR-146b and increased concentration of kynurenic acid.
Conclusion: Paternal and maternal obesity impair offspring's learning abilities by affecting different processes of memory formation. These cognitive deficits are associated with epigenetic and neurochemical alterations leading to impaired glutamate-mediated synaptic plasticity.
(© 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)
Databáze: MEDLINE
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