Degeneration and Repairβ-amyloid-induced gonadotropin-releasing hormone decline involving Forkhead transcription factor FOXO3a and nuclear factor-κBShi, Chuna,,b,,*; Shi, Rongjiec; Guo, Hana,,b; Shi, Yuchend; Liu, Xintonga,,*Author Information aDepartment of Neurology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong bDepartment of Anatomy, Dali University cDepartment of Gastroenterology, The First Affiliated Hospital of Dali University, Dali, Yunan dHengyang Medical College, Nanhua University, Hengyang, HuNan, China *Chun Shi and Xintong Liu contributed equally to the writing of this article. Received 30 April 2020 Accepted 6 May 2020 Correspondence to Chun Shi, PhD, Department of Neurology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong 510317, China, Tel: +86 19948727914; fax: +86 02084286790; e-mail: firstname.lastname@example.org NeuroReport: August 12, 2020 - Volume 31 - Issue 12 - p 923-927 doi: 10.1097/WNR.0000000000001488 Buy Metrics Abstract Previously, it has been demonstrated that aging is controlled by the hypothalamus, and that hypothalamus-driven programmatic aging is associated with nuclear factor-κB (NF-κB)-mediated gonadotropin-releasing hormone (GnRH) decrease. Abundant accumulation of β-amyloid (Aβ) has been observed in brains of cognitively normal elderly. However, it is unclear whether Aβ neurotoxicity is involved in aging-associated hypothalamic GnRH decline. GT1-7 cells, which are a cell line of hypothalamic GnRH neurons, were used in the current study to investigate whether and how Aβ decreased GnRH release. The results of the current study demonstrated that Aβ impaired the release of GnRH through activation of NF-κB. Mechanistic studies revealed that Aβ activated NF-κB via Forkhead box protein O3a, thereby inhibiting gnrh1 gene. The results of the present study provided novel insights into the mechanisms underlying aging-dependent hypothalamic GnRH decline. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.