Preventing, treating and predictiing barbering behavior in C57BL/6 mice

Barbering can be defined as an abnormal repetitive behavior in laboratory mice, where a barber mouse plucks fur or whiskers from the cagemates (hetero-barbering) or itself (self-barbering) in idiosyncratic patterns, leaving the cagemates with patches of missing fur and/or whiskers. Although barbering is highly prevalent in laboratory mice, especially in strains such as C57BL/6, the pathogenesis of barbering is not well understood. One of the proposed mechanisms of barbering is oxidative stress which has been implicated in the pathogenesis of several psychiatric disorders, since the brain is particularly vulnerable to oxidative damage. N-acetylcysteine (NAC), a precursor of glutathione (GSH), which is the most important antioxidant in our body, has been tested as a treatment for several neurodegenerative diseases. Indeed, NAC has been shown to be effective in the treatment of compulsive hair-pulling in humans. Therefore, the central hypothesis of this dissertation is that compulsive hair-pulling behavior in mice is caused by oxidative stress-induced damage of neurons. Firstly, our goal was to investigate both the efficacy of NAC in treating barbering behavior in mice and the association of biomarkers of oxidative stress and barbering behavior in mice. Our results suggest a positive relationship between barbering behavior and oxidative stress; barbering animals display higher levels of antioxidant production as a defense mechanism in response to oxidative stress. Our results showed that NAC can be effective in the prevention and/or treatment of barbering. Our data provides evidence that this occurs through the increase of GSH synthesis in the brain, thereby preventing oxidative damage. Animals with lower levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage and repair, are more likely to become barbers. However, the presence of biomarkers of oxidative stress in urine and blood are not specific to the location where the oxidative damage is happening. Whereas the oxidative process could be taking place in the brain, it also could be occurring in any part of the body. Gene expression studies encompassing the area of the brain believed to be involved in barbering will indicate if that region suffered apoptosis/oxidative damage. Therefore, our second objective was to verify if the brain was indeed suffering oxidative damage. RNA-Sequencing was used to detect differences in the gene expression between hair-pullers and control animals in the pre-frontal cortex. We predicted that genes in the oxidative stress pathway would be activated in barbers. Genes associated with neuronal development and survival were upregulated in hair-pullers, while ribosomal proteins were downregulated, indicating low metabolic activity in that particular area of the brain. Finally, the third objective was to evaluate if fur-chewing behavior in chinchillas is an oxidative stress condition. We tested if the antioxidant therapy with NAC would reduce the severity of compulsive hair-pulling in captive chinchillas. Although animals receiving NAC displayed a reduction in fur-chewing behavior, the females in the control group also showed a significant reduction. The experiments demonstrated that oxidative stress is indeed associated with compulsive barbering behavior and NAC has shown to be effective to reduce hair-pulling behavior in C57BL/6 mice. However, treatment efficacy varies between species, sex and reproductive status. A better understanding of the etiology and pathogenesis of compulsive hair-pulling will allow the development of effective therapies to improve the welfare not only of the laboratory mice but also other species affected by the condition