Circadian Clock Behavior Analysis
The Circadian clock generates physiological and behavioral rhythms with a period roughly 24 hours. It is thought that Circadian dysfunctions underlie the pathogenesis of many psychiatric disorders such as mania-like behavior and bipolar disorder (McClung, 2013). Attention Deficit Hyperactivity Disorder (ADHD) is one of the most widespread psychiatric disorders in humans. Somewhere between 3 and 5% of the population is affected by ADHD (Geissler and Lesch, 2011). The ADHD phenotype is characterized by increases in hyperactivity, inattentiveness and impulsivity (Kendal et al., 2008). Hyperactivity that results in sleep deprivation is one of the key behavioral manifestations of ADHD (Philipsen et al., 2006). Mice with the dominant negative Clock
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Adult humans with dysrhythmias of melatonin production and altered expression of the circadian clock genes BMAL1 and PER2 appear to have a higher incidence of adult ADHD (Baird et al., 2012). Circadian nuclear receptor Rev-erbα (Nr1d1) knock-out mice display mania-like behavior such as hyperactivity and a central hyperdopaminergic state (Chung et al. 2014). Per1 knock-out mice also display ADHD-like symptoms and reduced levels of dopamine. This indicates that a disruption of a circadian clock gene a elicits ADHD-like syndrome more generally. Zebrafish with circadian gene period1b (per1b) mutations display hyperactive, impulsive-like and ADHD-like behaviors as well as low levels of dopamine. This trend across three different species indicates a strong correlation between Circadian clock, dopamine and ADHD like behaviors. The circadian model for understanding ADHD sheds light on the pathogenesis and could potentially open avenues for exploring novel targets for diagnosis and therapy for this common psychiatric disorder. Huang et al. show that zebrafish mutants with per1b mutation display hyperactivity, impulsivity-like and inattentive-like behaviors as well as low levels of dopamine (DA), reminiscent of human ADHD …show more content…
Studying the physiological basis for ADHD like behaviors in per1b mutant zebrafish showed that per1b mutant zebrafish had significantly lower levels of DA than wild types further strengthening the link between per1b and ADHD-like behavior. Human ADHD is characterized by similarly low levels of DA. The circadian rhythm has been implicated in regulating DA synthesis, metabolism and signaling. The experimenters found that mao, a gene which encodes mooamineoxidases for decomposing DA, was upregulated in per1b mutant zebrafish. The mutant population was shown to additionally have excess β hydroxylase (dbh) which converts DA into NE. It was also observed that there was a significant phase difference (about 8 hrs) between per1b and wild type population rev-erbα expression which inhibits mechanisms associated with the production of mao and dbh. This effect is also found in mice and is likely responsible for the irregularities in DA levels in the mutant
Adult humans with dysrhythmias of melatonin production and altered expression of the circadian clock genes BMAL1 and PER2 appear to have a higher incidence of adult ADHD (Baird et al., 2012). Circadian nuclear receptor Rev-erbα (Nr1d1) knock-out mice display mania-like behavior such as hyperactivity and a central hyperdopaminergic state (Chung et al. 2014). Per1 knock-out mice also display ADHD-like symptoms and reduced levels of dopamine. This indicates that a disruption of a circadian clock gene a elicits ADHD-like syndrome more generally. Zebrafish with circadian gene period1b (per1b) mutations display hyperactive, impulsive-like and ADHD-like behaviors as well as low levels of dopamine. This trend across three different species indicates a strong correlation between Circadian clock, dopamine and ADHD like behaviors. The circadian model for understanding ADHD sheds light on the pathogenesis and could potentially open avenues for exploring novel targets for diagnosis and therapy for this common psychiatric disorder. Huang et al. show that zebrafish mutants with per1b mutation display hyperactivity, impulsivity-like and inattentive-like behaviors as well as low levels of dopamine (DA), reminiscent of human ADHD …show more content…
Studying the physiological basis for ADHD like behaviors in per1b mutant zebrafish showed that per1b mutant zebrafish had significantly lower levels of DA than wild types further strengthening the link between per1b and ADHD-like behavior. Human ADHD is characterized by similarly low levels of DA. The circadian rhythm has been implicated in regulating DA synthesis, metabolism and signaling. The experimenters found that mao, a gene which encodes mooamineoxidases for decomposing DA, was upregulated in per1b mutant zebrafish. The mutant population was shown to additionally have excess β hydroxylase (dbh) which converts DA into NE. It was also observed that there was a significant phase difference (about 8 hrs) between per1b and wild type population rev-erbα expression which inhibits mechanisms associated with the production of mao and dbh. This effect is also found in mice and is likely responsible for the irregularities in DA levels in the mutant