| Title: |
Obesity-Induced Memory Deficits in Female Rats Are Oestrous Cycle Dependent and Linked to Impaired Brain Kynurenine Pathway Metabolism |
| Authors: |
Mezo-González, Carla Elena; García Santillán, Juan Antonio; Reyes-Castro, Luis Antonio; Gourdel, Mathilde; Croyal, Mikaël; Bolaños-Jiménez, Francisco |
| Contributors: |
Physiopathologie des Adaptations Nutritionnelles (PhAN); Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran Mexico (INCMNSZ); Nantes Université (Nantes Univ); ANR-16-CE21-0007,NuTTTMeD,Analyse interculturelle intégrative de l'impact des transitions alimentaires sur les facteurs biologiques et socio-économiques qui déterminent le risque de maladie métabolique chez la progéniture de mères obèses.(2016) |
| Source: |
ISSN: 0028-3835. |
| Publisher Information: |
CCSD; Karger |
| Publication Year: |
2023 |
| Collection: |
Université de Nantes: HAL-UNIV-NANTES |
| Subject Terms: |
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/36580896; PUBMED: 36580896; WOS: 000910504400001 |
| DOI: |
10.1159/000528856 |
| Availability: |
https://hal.inrae.fr/hal-04327080; https://doi.org/10.1159/000528856 |
| Accession Number: |
edsbas.EDFDBD3E |
| Database: |
BASE |