BioProject

Behaviour can be seen as the outlet of the brains’ orchestra, chemistry and functionality. More...

Behaviour can be seen as the outlet of the brains’ orchestra, chemistry and functionality. Factors which change brain gene-expression can make individual’s develop certain unwanted behavioural traits. Alterations from normal tissue specific gene-expression have been associated with various neurodevelopmental disorders (Millan, 2012). These disorders in humans are generally diagnosed and categorized based on occurrences of specific behaviour problems or patterns combined with information on genetic predisposition, a person’s personality, mood and affect (DSM-5, American Psychiatric Association, 2018). Many behaviourally defined neurodevelopmental disorders (i.e. Attention Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Obsessive-Compulsive Disorder, and Tourette Syndrome) appear to have a strong overlapping genetic basis coordinating the brain’s stress response (Young et al., 2019). Some behavioural problems in animals appear similar to those in humans with regard to their aetiology, phenomenology and underlying neurobiology. One of these is feather pecking in chicken and its similarity with body-focussed repetitive behaviour (BFRBs) in humans. While in feather pecking, chickens peck the feathers of other chickens, in humans BFRBs are generally focused on one self’s body. BFRBs are commonly seen as a behavioural addiction (Conelea et al., 2017). Several compulsive grooming habits fall under the BFRBs criteria, such as hair pulling (trichotillomania), skin picking and nail biting (Greenberg, 2019). Especially more severe and damaging manifestations of these BFRBs seem to be difficult to inhibit or to stop when initiated i.e. they appear compulsive and perseverating (Houghton et al., 2018). Some BFRBs can be reduced with selective serotonin reuptake inhibitor (SSRI) treatments (Chamberlain et al., 2009). In chickens, feather pecking also reduces with drugs affecting serotonin reuptake (de Haas and Van der Eijk, 2018). A genetic predisposition together with (early life) stressful conditions can result in the development of BFRBs (Moon-Fabelli et al., 1999). For chickens a deprivation of environmental resources, especially in early life, can result in feather pecking (de Jong et al., 1998; de Haas et al., 2013b; Tahtahami et al., 2016) which can further sustain or reoccur in adulthood (Bestman et al., 2006; Gilani et al., 2014). Feather pecking is generally seen as a redirected behaviour, occurring under stressful conditions (El-lethey et al., 2000 and 2001) and in predisposed anxious individuals (Piepho et al., Rodenburg et al., 2004) - which is also known for BFRBs in humans (Chamberlain et al., 2009). Only some birds develop a behaviour disorder while others not, despite identical genetic background and environment (for chickens; van der Eijk et al., 2018; Daigle et al., 2015; Kops et al., 2013) - indicating that in these individuals more is going on. Brain epigenetics could help in understanding the risk of development of behavioural disorders (Roth and Sweatt, 2011). A very stable marker of epigenetics is DNA methylation, where a methyl group is added to the DNA at the C5 position to the DNA cytosine ring (Brummelte et al., 2017). Most commonly DNA methylation occurs at CpG dinucleotides. DNA methylation can modify gene-expression, mostly leading to turning the gene off. DNA methylation are key regulators of brain site-specific gene expression seen in many neurological disorders, associated with altered behaviour such as schizophrenia, depression and addiction (Bredy, 2007), autism (Loke et al., 2015), anxiety (Vonderwalde, 2019) and hyperactivity disorder (Babenko et al., 2014). Changes in whole-brain gene-expression patterns have also been found in chickens which perform feather pecking vs. controls (Lutz et al., 2017; Wysocki et al., 2013;Brunberg et al., 2012;). The differently expressed genes were related to neurotransmission (Lutz et al., 2017; Wysocki et al., 2013), immunology and obsessive compulsive disorders genes (Brunberg et al., 2012). Interestingly, obsessive compulsive disorder – i.e. repeatedly performing a behavioural act compulsively - has been, similarly, linked with alterations in immunology in humans (da Rocha et al., 2007). Selection on one specific behavioural trait (namely feather pecking) can give rise to associated traits being selected for, i.e. many genes may contribute a small effect (Jensen, 2014). The link between differently affected genes due to selection on behaviour can aid in understanding the genetic mechanisms underlying behavioural disorders. In this study we compared both genetic and epigenetic differences in chickens divergently selected on feather pecking (i.e. a high and low line). We specifically looked at DNA-methylation in the thalamus as this region is important for regulation of stress, and it plays a strong role in the aetiology of neurodevelopmental disorders (Millan, 2012). By comparing differently methylation regions between two chicken lineages, we could disentangle the influence of genetics and brain-epigenetics on the selection on feather pecking. Our chicken feather pecking model has been selected for many generation, and as such could be providing a new animal model for the study of behavioural disorders in humans. Less...