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PreprintCited by 8Stress Responses and CortisolTryptophan and brain disordersNeuropeptides and Animal Physiology

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Chronic kidney disease may evoke anxiety by altering CRH expression in the amygdala and tryptophan metabolism in rats

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Ibos, Katalin Eszter, Bodnár, Éva, Dinh, Hoa, Kiss, Merse, Márványkövi, Fanni, Kovács, Zsuzsanna Z. A., Siska, Andrea, Földesi, Imre, Galla, Zsolt, Monostori, Péter, Szatmári, István, Simon, Péter, Sárközy, Márta, Csabafi, Krisztina·2023·Pflügers Archiv - European Journal of Physiology
DOI 10.21203/rs.3.rs-3111616/v1PMC PMC10791708

Preprint — published as 10.1007/s00424-023-02884-y · Paper page

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Abstract

Chronic kidney disease (CKD) is associated with anxiety; however, its exact mechanism is not well understood. Therefore, the aim of the present study was to assess the effect of moderate CKD on anxiety in rats. 5/6 nephrectomy was performed in male Wistar rats. 7 weeks after, anxiety-like behavior was assessed by elevated plus maze (EPM), open field (OF), and marble burying (MB) tests. At weeks 8 and 9, urinalysis was performed, and blood and amygdala samples were collected, respectively. In the amygdala, the gene expression of Avp, as well as the gene and protein expression of Crh, Crhr1, and Crhr2 were analyzed. Furthermore, the plasma concentration of corticosterone, uremic toxins, and tryptophan metabolites were measured by UHPLC-MS/MS. Laboratory tests confirmed the development of CKD. In the CKD group, the closed arm time increased, the central time and the total number of entries decreased in the EPM. There was a reduction in rearing, central distance and time in the OF, and fewer interactions with marbles were detected during MB. CKD evoked an upregulation of Crh, Crhr1, and Crhr2 genes in the amygdala, but protein expression did not change. In the CKD group, plasma concentrations of p-cresyl-sulfate, indoxyl-sulfate, kynurenine, kynurenic acid, 3-hydroxykynurenine, anthranilic acid, xanthurenic acid, 5-hydroxyindoleacetic acid, picolinic acid, and quinolinic acid increased. However, the levels of tryptophan, tryptamine, 5-hydroxytryptophan, serotonin, and tyrosine decreased. In conclusion, moderate CKD evoked anxiety-like behavior that might be mediated by the upregulation of the amygdalar CRH system, uremic toxins and metabolites of the kynurenine pathway.

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Metadata

Authors
Ibos, K. E., Bodnár, É., Dinh, H., Kiss, M., Márványkövi, F., Kovács, Z. Z. A., Siska, A., Földesi, I., Galla, Z., Monostori, P., Szatmári, I., Simon, P., Sárközy, M., & Csabafi, K.
Affiliations
  • University of Szeged (HU)
  • Bạch Mai Hospital (VN)
  • Department of Biochemistry and Interdisciplinary Centre of Excellence, Albert Szent-Györgyi Medical School, University of Szeged
Corresponding author
Ibos, Katalin Eszter
ORCID
Venue
Pflügers Archiv - European Journal of Physiology
Publisher
Research Square Platform LLC
Published
2023-07-03
Volume
476
Issue
2
Pages
179-196
ISSN
0031-6768 (ISSN-L)
DOI
10.21203/rs.3.rs-3111616/v1
PMC
PMC10791708
OpenAlex
W4388880067
Cited by
8
References
1
Citations by year
2026: 2 · 2025: 4 · 2024: 2
FWCI
1.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Pflügers Archiv - European Journal of Physiology (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, cc-by)
  • Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion, cc-by)
Funders
  • Magyar Tudományos Akadémia (3.6.2-16-2017-00006, EFOP-3.6.2-16-2017-00006, GINOP-2.3.2-15-2016-00040)
  • Szegedi Tudományegyetem
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
chronic kidney disease, anxiety-like behavior, corticotropin-releasing factor, amygdala, CRH receptor 1, CRH receptor 2, vasopressin, tryptophan metabolism, kynurenine pathway, uremic toxins, serotonin, 5/6 nephrectomy
MeSH terms
Uremic Toxins, Amygdala, Animals, Anxiety, Kynurenine, Male, Tryptophan, Rats, Wistar, Rats, Renal Insufficiency, Chronic, Tandem Mass Spectrometry

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