Impaired Neurobehavioral Function in Belgrade Rats with Iron Loading Anemia, a Model of Thalassemia

Presenter: Jonghan Kim

Research Category: Health Sciences
Student Type: Graduate
PI: Jonghan Kim

Thalassemia is a hereditary anemic disease due to mutations in globin synthesis and therefore requires blood transfusion. This treatment increases iron levels in the circulation and promotes iron loading anemia. Although iron is essential for brain development and monoamine homeostasis, iron loading in the brain is implicated in several neurological problems. However, whether or not iron loading anemia modifies cognitive and emotional behavior is largely unknown. In order to characterize the neurobehavioral performance, we used Belgrade rats, a model of iron loading anemia that resembles thalassemia. Homozygous Belgrade rats (b/b) and control heterozygous rats (+/b) (11-12 weeks old) were subject to a battery of behavioral tests, including novel object recognition, elevated plus maze, Barnes maze and rotarod. The b/b rats did not alter memory capacity determined by novel object recognition task or Barnes maze test. In the elevated plus maze test, however, b/b rats showed significantly reduced anxiety-like behavior with increased time in the open arms (14% increase; p=0.008) and decreased time in the closed arms (19% decrease; p=0.006), compared with controls. Also, motor skills were impaired in b/b rats, as assessed by rotarod (13% decrease in speed; p=0.020). Western blot analysis demonstrated elevated levels of dopamine D1 receptor (D1DR; 905% increase) with altered monoamine transporters. Overall, our results suggest that iron loading anemia is associated with decreased anxiety and impaired motor coordination, possibly due to altered dopamine metabolism and elevated D1DR signaling.