The neuroprotective effect of LCZ696 on methamphetamine-induced cognitive impairment in mice.
Neurosci Lett
; 823: 137630, 2024 Feb 16.
Article
en En
| MEDLINE
| ID: mdl-38215873
ABSTRACT
OBJECTIVE:
Methamphetamine (METH) exposure commonly causes cognitive impairment. An angiotensin II receptor/neprilysin inhibitor (ARNI), LCZ696 has been demonstrated to inhibit inflammation, oxidative stress and apoptosis. The present study was designed to examine the effect of LCZ696 on METH-induced cognitive impairment and the underlying mechanism.METHODS:
Following daily treatment of either saline or METH (5 mg/kg) for 5 consecutive days, the cognitive function was tested using the Y-maze and the Novel Object Recognition (NOR) in Experiment 1. In Experiment 2, mice were initially treated with saline or LCZ696 (60 mg/kg) for 9 consecutive days, followed by LCZ696, METH or saline for 5 days. Cognitive testing was carried out as Experiment 1. In Experiment 3, SH-SY5Y cells were treated with either METH (2.5 Mm) or ddH2O for 12 h. The apoptosis and reactive oxygen species (ROS) level of SH-SY5Y were examined. In Experiment 4, SH-SY5Y cells were pretreated with either ddH2O or LCZ696 (70um) for 30 min, followed by ddH2O or METH treatment for 12 h. Nrf2 and HO-1 protein expression was examined in the ventral tegemental area (VTA) of all the animals and SH-SY5Y cells.RESULTS:
LCZ696 significantly improved METH-induced cognitive impairment, in conjunction with decreased apoptosis and ROS levels in VTA of METH-treated mice and SH-SY5Y cells. METH significantly decreased Nrf2 and HO-1 protein expression in VTA of mice and SH-SY5Y cells, which was reversed by LCZ696 treatment.CONCLUSION:
LCZ696 yields a neuroprotective effect against METH-induced cognitive dysfunction via the Nrf2/HO-1 signaling pathway.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos de Bifenilo
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Fármacos Neuroprotectores
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Disfunción Cognitiva
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Valsartán
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Aminobutiratos
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Metanfetamina
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Neuroblastoma
Límite:
Animals
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Humans
Idioma:
En
Revista:
Neurosci Lett
Año:
2024
Tipo del documento:
Article
País de afiliación:
China