Calcitriol attenuates lipopolysaccharide-induced neuroinflammation and depressive-like behaviors by suppressing the P2X7R/NLRP3/caspase-1 pathway.
Psychopharmacology (Berl)
; 241(7): 1329-1343, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38411637
ABSTRACT
RATIONALE Microglia-mediated neuroinflammation is a vital hallmark in progression of depression, while calcitriol exerts anti-inflammatory effects in the brain. The activation of the P2X7 receptor has an important link to neuroinflammation. However, it is unclear whether calcitriol treatment exerts anti-inflammatory effects in association with P2X7R activation. OBJECTIVE:
In this study, we assessed the antidepressive and neuroprotective effects of calcitriol on lipopolysaccharide (LPS)-mediated depressive-like behavior, neuroinflammation, and neuronal damage.METHODS:
In in vitro experiments, the BV2 cells were exposed to LPS, and the protective effects of calcitriol were assessed. For in vivo experiment, thirty-two male C57BL/6 mice were divided into four groups of control, calcitriol, LPS and LPS + calcitriol. Calcitriol was administered at 1 µg/kg for 14 days and LPS at 1 mg/kg once every other day for 14 days. The control group mice were given equal volumes of vehicles. All treatments were delivered intraperitoneally.RESULTS:
The in vitro experiments showed calcitriol inhibited the release of inflammatory mediators induced by LPS in BV2 cells. The in vivo experiments revealed that calcitriol alleviated LPS-induced behavioral abnormalities and spatial learning impairments. Moreover, calcitriol treatment reduced the mRNA levels of pro-inflammatory cytokines, while increasing anti-inflammatory cytokine levels in the hippocampus. Our results further revealed that calcitriol administration attenuated LPS-induced microglia activation by suppressing P2X7R/NLRP3/caspase-1 signaling. Moreover, calcitriol inhibited apoptosis of neurons in the hippocampus as evidenced by expression of apoptosis-related proteins and TUNEL assay.CONCLUSIONS:
Collectively, our findings demonstrated that calcitriol exerts antidepressive and neuroprotective effects through the suppression of the P2X7R/NLRP3/caspase-1 pathway both in LPS-induced inflammation models in vitro and in vivo.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Calcitriol
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Lipopolissacarídeos
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Microglia
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Caspase 1
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Depressão
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Receptores Purinérgicos P2X7
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Proteína 3 que Contém Domínio de Pirina da Família NLR
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Doenças Neuroinflamatórias
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Camundongos Endogâmicos C57BL
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article