Antagonism for NPY signaling reverses cognitive behavior defects induced by activity-based anorexia in mice

• Published in: Psychoneuroendocrinology 2021-04, Vol.126, p.105133-105133, Article 105133
• Main Authors: Rokot, Natasya Trivena, Ataka, Koji, Iwai, Haruki, Suzuki, Hajime, Tachibe, Homare, Kairupan, Timothy Sean, Cheng, Kai-Chun, Amitani, Haruka, Inui, Akio, Asakawa, Akihiro
• Format: Article
• Language: English
• Subjects: Agouti-related peptide; Agouti-Related Protein - metabolism; Animals; Anorexia - chemically induced; Anorexia - metabolism; Anorexia nervosa; Arcuate Nucleus of Hypothalamus - metabolism; Cognition; Cognitive behavior; Female; Humans; Hypothalamus - metabolism; Mice; Mice, Inbred C57BL; Neuropeptide Y; Neuropeptide Y - metabolism; RNA, Messenger; Y5 receptor
• ISSN: 0306-4530; 1873-3360
• DOI: 10.1016/j.psyneuen.2021.105133

Patients with AN often express psychological symptoms such as body image distortion, cognitive biases, abnormal facial recognition, and deficits in working memory. However, the molecular mechanisms underlying the impairment of cognitive behaviors in AN remain unknown. In the present study, we measured cognitive behavior using novel object recognition (NOR) tasks and mRNA expressions in hypothalamic neuropeptides in female C57BL/6J mice with activity-based anorexia (ABA). Additionally, we evaluated the effects of antagonists with intracerebroventricular (icv) administration on the impairment of cognitive behavior in NOR tasks. Our results showed that NOR indices were lowered, subsequently increasing mRNA levels of agouti-related peptide (AgRP) and neuropeptide Y (NPY), and c-Fos- and AgRP- or NPY-positive cells in the hypothalamic arcuate nucleus in ABA mice. We also observed that icv administration of anti-NPY antiserum (2 µl), anti-AgRP antibody (0.1 μg), and Y5 receptor antagonist CPG71683 (15 nmol) significantly reversed the decreased NOR indices. Therefore, our results suggest that increased NPY and AgRP signaling in the brain might contribute to the impairment of cognitive behavior in AN. [Display omitted] •Activity-based anorexia (ABA) is a well validated model for anorexia nervosa (AN).•AN causes the body image distortion, cognitive biases, and the deficit of working memory.•We observed the defect of novel object recognition behaviors in ABA model mice.•These defect were reversed by anti-NPY antiserum, anti-AgRP antibody, and Y5 receptor antagonist.