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Protective effects of melatonin against oxidative stress in Fmr1 knockout mice: a therapeutic research model for the fragile X syndrome
Author(s) -
RomeroZerbo Yanina,
Decara Juan,
El Bekay Rajaa,
SanchezSalido Lourdes,
Del ArcoHerrera Ignacio,
De Fonseca Fernando Rodríguez,
De DiegoOtero Yolanda
Publication year - 2009
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2008.00653.x
Subject(s) - fmr1 , melatonin , oxidative stress , knockout mouse , fragile x syndrome , endocrinology , medicine , glutathione , tianeptine , biology , antidepressant , biochemistry , genetics , hippocampus , fragile x , receptor , gene , enzyme
Fragile X syndrome is the most common form of inherited mental retardation. It is typically caused by a mutation of the Fragile X mental‐retardation 1 (Fmr1) gene. To better understand the role of the Fmr1 gene and its gene product, the fragile X mental‐retardation protein in central nervous system functions, an fmr1 knockout mouse that is deficient in the fragile X mental‐retardation protein was bred. In the present study, fragile X mental retardation 1‐knockout and wild‐type mice are used to determine behaviour and oxidative stress alterations, including reduced glutathione, oxidized glutathione and thiobarbituric acid‐reactive substances, before and after chronic treatment with melatonin or tianeptine. Reduced glutathione levels were reduced in the brain of fmr1‐knockout mice and chronic melatonin treatment normalized the glutathione levels compared with the control group. Lipid peroxidation was elevated in brain and testes of fmr1‐knockout mice and chronic melatonin treatment prevents lipid peroxidation in both tissues. Interestingly, chronic treatment with melatonin alleviated the altered parameters in the fmr1‐knockout mice, including abnormal context‐dependent exploratory and anxiety behaviours and learning abnormalities. Chronic treatment with tianeptine (a serotonin reuptake enhancer) did not normalize the behaviour in fmr1‐knockout mice. The prevention of oxidative stress in the fragile X mouse model, by an antioxidant compound such as melatonin, emerges as a new and promising approach for further investigation on treatment trials for the disease.