Long-term efavirenz exposure induced neuroinflammation and cognitive deficits in C57BL/6 mice.
Biochem Biophys Res Commun
; 584: 46-52, 2021 12 20.
Article
in En
| MEDLINE
| ID: mdl-34768081
ABSTRACT
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI), which is widely used for anti-HIV-1. Evidences revealed that several central nervous system side effects could be observed in mice and patients with administration of EFV. However, the detailed mechanisms are still unknown. In this study, we investigated the effects of long-term EFV treatment on cognitive functions and the potential underlying mechanisms in mice. We maintained C57BL/6 mice aged 2 months with treatment containing 40 or 80 mg/kg/day EFV for 5 months, while control group treated with saline. The cognitive functions were evaluated by novel object recognition test, Barnes maze test and Morris water maze. The results showed significant short-term memory impairment in 40 and 80 mg/kg groups, and notable spatial learning and memory impairments in 80 mg/kg group, without any spontaneous activity alteration. Moreover, EFV induced impairments in dendritic integrity and synaptic plasticity in hippocampus. Furthermore, Significant increases were observed in the expression levels of pro-IL-1ß, a similar tendency of TNF-α and phosphorylation of p65 of the 80 mg/kg group compared with control group. These results imply that long-term EFV treatment causes synaptic dysfunction resulting in cognitive deficits, which might be induced by the enhanced pro-inflammatory cytokines IL-1ß and TNF-α via activating NF-κB pathway.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cognition
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Cyclopropanes
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Benzoxazines
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Alkynes
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Cognitive Dysfunction
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Neuroinflammatory Diseases
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Memory Disorders
Limits:
Animals
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Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2021
Document type:
Article
Affiliation country:
China