The effect of Vortioxetine on the NLRP3 pathway and microglial activity in the prefrontal cortex in an experimental model of depression

BACKGROUND: Increasing evidence suggests that early life stress (ELS) and neuroinflammation are associated with the pathophysiology of depression. The purpose of this study was to determine the effects of Vortioxetine (VOR), a novel antidepressant, on ELS-induced behavioral changes and neuroinflammation.

METHOD: Wistar Albino 4-week-old male rats were divided into four groups: control; chronic unpredictable stress (CUMS), VOR, CUMS + VOR. Neurobehavioral assessment was performed on the first, 21st, and 42nd days. RT-PCR was used to detect the expression of P2X7, NLRP3, IL1β, IL18 in the prefrontal cortex. To assess the microglial activities of the prefrontal cortex, immunohistochemically stained CD68, and leukocyte common antigen (LCA) preparations were scanned with Manual WSI software, Basler camera, and scored.

RESULT AND DISCUSSION: Exposure to CUMS was associated with depression and anxiety-like behaviors, and administration of VOR led to improvement in these behaviors. NLRP3, IL-1β, and IL-18 were shown to be upregulated in the prefrontal cortex of CUMS rats, while their high expression was inhibited by VOR treatment. CD68 and LCA expressions were significantly higher in the CUMS group compared to the other groups.

CONCLUSION: According to these results, it may be considered that NLRP3 inflammasome-associated neuroinflammatory response and microglial activation may play a role in the etiopathogenesis of ELS.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:46

Enthalten in:

Immunopharmacology and immunotoxicology - 46(2024), 2 vom: 31. März, Seite 264-275

Sprache:

Englisch

Beteiligte Personen:

Ozdamar Unal, Gulin [VerfasserIn]
Kumbul, Duygu [VerfasserIn]
Hekimler Ozturk, Kuyas [VerfasserIn]
Erkılınc, Gamze [VerfasserIn]
Donmez, Feyza [VerfasserIn]
Dogan Kıran, Eltaf [VerfasserIn]
Yuceer, Ramazan Oğuz [VerfasserIn]

Links:

Volltext

Themen:

3O2K1S3WQV
Early life stress
Inflammasomes
Journal Article
Microglia
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3
Neuroinflammation
Vortioxetine

Anmerkungen:

Date Completed 25.03.2024

Date Revised 25.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1080/08923973.2024.2308268

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM367747677