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Study M992

Study name

Xie W 2014

Title

Activation of brain indoleamine 2,3-dioxygenase contributes to epilepsy-associated depressive-like behavior in rats with chronic temporal lobe epilepsy

Overall design

The aim of this study was to explore whether indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism, plays a key role in epilepsy-associated depressive-like behavior. In the first part of this study, Wistar rats were divided into the following 2 groups: (1) control group, and (2) pilocarpine group. Rats in the pilocarpine group received a subcutaneous injection of pilocarpine hydrochloride (40 mg/kg), then rats exhibited continuous generalized clonic-tonic seizures lasting at least 2 hours. Rats which develop chronic epilepsy following pilocarpine status epilepticus exhibited a set of interictal disorders consistent with depressive-like behavior 6 weeks later. Oral gavage of minocycline or subcutaneous injection of 1-methyltryptophan were then used to inhibit IDO1 expression. In the second part of this study, Wistar rats were divided into the following 4 groups: (1) control group, (2) pilocarpine group, (3) 1-methyltryptophan group, and (4) pilocarpine + 1-methyltryptophan group. 1-Methyltryptophan was administered through subcutaneous injection at 50 mg/kg, twice daily between 6 and 8 weeks after pilocarpine injection. In the third part of this study, Wistar rats were divided into the following 4 groups: (1) control group, (2) pilocarpine group, (3) minocycline group, and (4) pilocarpine + minocycline group. Minocycline was administered at 120 mg/kg through gavage, twice daily between 6 and 8 weeks after pilocarpine injection. Brain kynurenine/tryptophan and serotonin/tryptophan ratios were analyzed by liquid chromatography-mass spectrometry (n =5-6/group).

Study Type

Type1;

Type2;

Type3;

Data available

Unavailable

Organism

Rat; Wistar rat;

Categories of depression

Animal model; Other animal model; Other animal model;

Healthy individuals; Healthy individuals; Healthy individuals;

Criteria for depression

Saccharin solution consumption test, forced swimming test

Sample size

53

Tissue

Central; Brain; Hippocampus;

Platform

MS-based; LC-MS: Prominence 20A series UFLC System (Shimadzu, Kyoto, Japan) with API 4000 Qtrap MS System (ABSciex, Massachusetts, USA);

PMID

24594021

DOI

10.1186/1742-2094-11-41

Citation

Xie W, Cai L, Yu Y, et al. Activation of brain indoleamine 2,3-dioxygenase contributes to epilepsy-associated depressive-like behavior in rats with chronic temporal lobe epilepsy. J Neuroinflammation. 2014 Mar 4;11:41.

Metabolite

Kynurenine/Tryptophan ratio;

Serotonin/Tryptophan ratio;