Obesity-Induced Memory Deficits in Female Rats Are Oestrous Cycle Dependent and Linked to Impaired Brain Kynurenine Pathway Metabolism.

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., Reyes-Castro LA; Reproductive Biology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Gourdel M; CRNH-O Mass Spectrometry Core Facility, Nantes, France.; Nantes Université, CNRS, INSERM, L'institut du Thorax, Nantes, France.; Nantes Université, CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016, CNRS UMS 3556, Nantes, France., Croyal M; CRNH-O Mass Spectrometry Core Facility, Nantes, France.; Nantes Université, CNRS, INSERM, L'institut du Thorax, Nantes, France.; Nantes Université, CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016, CNRS UMS 3556, Nantes, France., Bolaños-Jiménez F; UMR Physiologie des Adaptations Nutritionnelles, INRAE - Nantes Université, Nantes, France.
Jazyk:	angličtina
Zdroj:	Neuroendocrinology [Neuroendocrinology] 2023; Vol. 113 (5), pp. 549-562. Date of Electronic Publication: 2022 Dec 29.
DOI:	10.1159/000528856
Abstrakt:	Introduction: Obesity is associated with impaired learning, but the mechanisms underlying this cognitive dysfunction are poorly understood. Moreover, whether obesity-induced learning deficits show sexual dimorphism remains controversial. Females are believed to be protected from cognitive decline by oestrogens. These hormones enhance the expression of tryptophan hydroxylase 2, the rate-limiting enzyme in the transformation of tryptophan (Trp) into serotonin which plays a significant role in learning and memory. However, several learning-regulating compounds also arise from Trp metabolism through the kynurenine pathway (KP), including kynurenic acid (KA), xanthurenic acid (XA), and NAD+. The present study aimed to determine the involvement of the KP of Trp metabolism in the regulation of learning in control and obese female rats. Methods: The learning capabilities of control and obese rats were evaluated using the novel object recognition test. Trp and Trp-derived metabolites were quantified in the hippocampus and frontal cortex by ultra-performance liquid chromatography-tandem mass spectrometry. Results: Control rats in proestrus/oestrous performed better than their control mates in metestrus/dioestrus. Likewise, while control and obese rats in dioestrus/metestrus did not show differences in learning, obese rats in proestrus/oestrous displayed decreased memory capacity along with decreased Trp concentration and reduced KA, XA, and NAD+ production in the hippocampus. These neurochemical alterations were associated with impaired expression of mRNAs coding for key enzymes of the KP. Conclusion: The results presented here indicate that the deleterious effects of obesity on learning are closely related to the oestrous cycle and associated with an impairment of the KP of Trp metabolism. (© 2022 S. Karger AG, Basel.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu