Interference of different anesthetic agents on behavior and oxidative stress in the animal model of Aβ1‐42‐induced dementia in mice.

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease. The animal model of AD‐like dementia induced by the peptide β‐amyloid 1‐42 (Aβ1‐42) is widely used. However, the animals have to be anesthetized and no studies are evaluating which anesthetic causes less interference in this model. This study aimed to evaluate the interference of different anesthetics on behavioral and oxidative stress in a mice model of Aβ1‐42‐induced dementia.MethodMale and female BALB/c mice at 3‐ month‐old were used under three different protocols. Protocol 1 (inhalation): (1) 100% oxygen (isoflurane control); (2) artificial cerebrospinal fluid (ACSF) + isoflurane; (3) Aβ1‐42 + isoflurane. Protocol 2 (intraperitoneal): (1) saline; (2) ACSF + ketamine + xylazine; (3) ACSF + ketamine + dexmedetomidine; (4) Aβ1‐42 + ketamine + xylazine; (5) Aβ1‐42 + ketamine + dexmedetomidine. Protocol 3 (intraperitoneal): (1) saline; (2) ACSF + propofol; (3) Aβ1‐42 + propofol. After the anesthesia, mice were injected with Aβ1‐42 (400 pmol) free‐hand intracerebroventricular, then after 13 days, mice were submitted to the Y‐maze test (spatial memory), plus‐maze (anxiety), and open‐field (habituation memory); then, hippocampus were dissected to analysis.ResultIsoflurane per se (protocol 1) caused no memory impairment, but caused an anxiolytic effect in males, in addition, to increased sulfhydryl content in males. In protocol 2, ACSF + ketamine + xylazine induced spatial memory impairment in males and habituation memory impairment in females; the anesthetics of protocol 2 increased 2',7' dichlorodihydrofluorescein (DCF) levels in females, and ACSF + ket + dex reduced levels of glutathione (GSH) in males. In protocol 3, propofol per se caused an anxiolytic effect in males and increased DCF levels in males and females, increased superoxide dismutase activity in males, and reduction in females, in addition, increased sulfhydryl content in males.ConclusionAll anesthetic protocols evaluated caused alterations in the behavior and/or oxidative stress parameters; however, isoflurane seems to cause less interference in the animal model, followed by propofol. Protocol 3 seems to cause more interference, including in the Y‐maze (spatial memory), which is one of the main behavior tests to evaluate the mice model of Aβ1‐42‐induced dementia.