Investigating the pathophysiology of anorexia nervosa using induced pluripotent stem cells

Abstract

Abstract Anorexia Nervosa (AN) is a multifactorial neuropsychiatric disease characterized by deregulations in the control of food intake and in reward processing. Brain imaging studies have shown that changes of both functions are underlined by abnormal activities of neuronal networks involving specific neuronal neurotransmission including serotoninergic and dopaminergic signaling. Whereas mouse models, either genetic or behavioral, are able to partially recapitulate phenotypes observed patients diagnosed with AN, they provide a limited amount of information about how interactions of altered brain functions are in human patients. Animal models also cannot integrate the multigenic risk factors and epigenetic deregulations that contribute to AN. Since 2012, it has been possible to generate in\xa0vitro cellular models of patients’ samples, as well as targeted mutagenesis and corrections of the human genome, using stem cell reprogramming processes and CRISPR-CAS9 technology. Further developments are currently underway to create three-dimensional models of human brain regions, improving cell–cell interaction and neuronal maturation. In this book chapter, while summarizing the main findings of (i)\xa0the epigenetics, (ii) brain imaging studies, and (iii) mouse models of AN, we review the information collected from induced pluripotent stem cell-derived models. These new findings suggest that investigating human cellular models of specific neuronal subtypes and their interactions will provide significant added value toward improving our knowledge of the pathophysiology of AN.