Neurobehavioral effects of uremic toxin-indoxyl sulfate in the rat model

Chronic kidney disease (CKD) is deemed to be a worldwide health concern connected with neurological manifestations. The etiology of central nervous system (CNS) disorders in CKD is still not fully understood, however particular attention is currently being paid to the impact of accumulated toxins. Indoxyl sulfate (IS) is one of the most potent uremic toxins. The purpose of the present study was to assess IS concentrations in the cerebellum, brainstem, cortex, hypothalamus, and striatum with hippocampus of rats chronically exposed to IS. To evaluate IS impact on neurochemical and behavioral alterations, we examined its influence on brain levels of norepinephrine, epinephrine, dopamine, serotonin and their metabolites, as well as changes in behavioral tests (open field test, elevated plus maze test, chimney test, T maze test, and splash test). Our results show the highest IS accumulation in the brainstem. IS leads to behavioral alterations involving apathetic behavior, increased stress sensitivity, and reduced locomotor and exploratory activity. Besides, IS contributes to the impairment of spatial memory and motor coordination. Furthermore, we observed reduced levels of norepinephrine, dopamine or serotonin, mainly in the brainstem. Our findings indicate that IS can be one of the crucial uremic factors responsible for altered mental status in CKD.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

Scientific reports - 10(2020), 1 vom: 11. Juni, Seite 9483

Sprache:

Englisch

Beteiligte Personen:

Karbowska, Malgorzata [VerfasserIn]
Hermanowicz, Justyna M [VerfasserIn]
Tankiewicz-Kwedlo, Anna [VerfasserIn]
Kalaska, Bartlomiej [VerfasserIn]
Kaminski, Tomasz W [VerfasserIn]
Nosek, Krzysztof [VerfasserIn]
Wisniewska, Roza J [VerfasserIn]
Pawlak, Dariusz [VerfasserIn]

Links:

Volltext

Themen:

333DO1RDJY
Dopamine
Indican
Journal Article
N187WK1Y1J
Norepinephrine
Research Support, Non-U.S. Gov't
Serotonin
Toxins, Biological
VTD58H1Z2X
X4W3ENH1CV

Anmerkungen:

Date Completed 30.11.2020

Date Revised 11.06.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-020-66421-y

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM311073670