Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023;113(5):549-562.
doi: 10.1159/000528856. Epub 2022 Dec 29.

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

Carla Elena Mezo-González  1 , Juan Antonio García Santillán  1 , Luis Antonio Reyes-Castro  2 , Mathilde Gourdel  3   4   5 , Mikaël Croyal  3   4   5 , Francisco Bolaños-Jiménez  1
Affiliations

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

Carla Elena Mezo-González et al. Neuroendocrinology. 2023.

Abstract

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.

Keywords: Kynurenine pathway; Learning; Obesity; Oestrous cycle; Sex differences; Tryptophan.

PubMed Disclaimer

Publication types