Cognitive impairment and hippocampal neuronal damage in β-thalassaemia mice

beta-Thalassaemia is one of the most common genetic diseases worldwide. During the past few decades, life expectancy of patients has increased significantly owing to advance in medical treatments. Cognitive impairment, once has been neglected, has gradually become more documented. Cognitive impairment in beta-thalassaemia patients is associated with natural history of the disease and socioeconomic factors. Herein, to determined effect of beta-thalassaemia intrinsic factors, 22-month-old beta-thalassaemia mouse was used as a model to assess cognitive impairment and to investigate any aberrant brain pathology in beta-thalassaemia. Open field test showed that beta-thalassaemia mice had decreased motor function. However, no difference of neuronal degeneration in primary motor cortex, layer 2/3 area was found. Interestingly, impaired learning and memory function accessed by a Morris water maze test was observed and correlated with a reduced number of living pyramidal neurons in hippocampus at the CA3 region in beta-thalassaemia mice. Cognitive impairment in beta-thalassaemia mice was significantly correlated with several intrinsic beta-thalassaemic factors including iron overload, anaemia, damaged red blood cells (RBCs), phosphatidylserine (PS)-exposed RBC large extracellular vesicles (EVs) and PS-exposed medium EVs. This highlights the importance of blood transfusion and iron chelation in beta-thalassaemia patients. In addition, to improve patients' quality of life, assessment of cognitive functions should become part of routine follow-up.