NADPH oxidase-derived production of reactive oxygen species is involved in learning and memory impairments in 16-month-old female rats

Kan,Hongwei; Hu,Wen; Wang,Yuchan; Wu,Wangyang; Yin,Yanyan; Liang,Yan; Wang,Chunyan; Huang,Dake; Li,Weizu

doi:10.3892/mmr.2015.3894

NADPH oxidase-derived production of reactive oxygen species is involved in learning and memory impairments in 16-month-old female rats

Authors:
- Hongwei Kan
- Wen Hu
- Yuchan Wang
- Wangyang Wu
- Yanyan Yin
- Yan Liang
- Chunyan Wang
- Dake Huang
- Weizu Li
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Affiliations: Department of Pharmacology, Key Laboratory of Anti‑Inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Laboratory of Pharmacology, Anhui Institute of Materia Medica, Hefei, Anhui 230022, P.R. China, Synthetic Laboratory of Basic Medicine College, Anhui Medical University, Hefei, Anhui 230032, P.R. China
Published online on: June 8, 2015 https://doi.org/10.3892/mmr.2015.3894
Pages: 4546-4553

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Abstract

Women undergoing the natural menopause can experience progressive cognitive dysfunction, particularly in the form of memory impairment. However, the mechanisms underlying memory impairments in the menopause remain to be elucidated. There is increasing evidence that oxidative damage caused by excessive reactive oxygen species (ROS) production may correlate with age‑associated cognitive impairment. The nicotinamide adenosine dinucleotide phosphate oxidase (NOX) family is important in the generation of ROS in the brain. It has been hypothesized that the accumulation of ROS, derived from NOX, may be involved in menopause‑associated learning and memory impairments. The present study investigated whether NOX‑derived ROS generation affected the learning and memory ability in 3‑month and 16‑month‑old female rats. The results of a morris water maze assessment revealed that there were significant learning and memory impairments in the 16‑month‑old female rats. Furthermore, the activity of superoxide dismutase (SOD), level of malondialdehyde (MDA), production of ROS and expression levels of NOX2, p47phox, Ras‑related C3 botulinum toxin substrate 1 (RAC1) and protein kinase C α (PKCα) were investigated in the cortex and hippocampus of 3‑month and 16‑month old female rats. The results demonstrated that the activity of SOD was significantly decreased, whereas the levels of MDA, production of ROS and expression levels of NOX2, p47phox, RAC1 and PKCα were significantly increased in the 16‑month old female rats. These results suggested that NOX‑mediated oxidative stress may be important in menopause‑associated learning and memory impairments.

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