Alterations in morphology and barrier function of tanycytes in an APP/PS1 transgenic mouse model of Alzheimer’s disease

Abstract

Abstract Hypothalamic defects characterized by metabolic disorders influence the progression of Alzheimer’s disease (AD). Recent studies have proposed that tanycytes, radial glial-like cells lining the third ventricle wall, participate in energy homeostasis regulation as an important player. However, the role of tanycytes in neurodegenerative diseases such as AD is unclear. Our ongoing research aims to investigate morphological and functional changes in tanycytes in an APP/PS1 mouse model of AD. Considering the spatial distribution of hypothalamic nuclei, we focused on middle region (from bregma − 1.5 to − 2.1 mm) of the mediobasal hypothalamus. By vimentin immunostaining, we found both internal and external ME areas occupied by vimentin-positive processes displayed a significant reduction in 12-month-old APP/PS1 mice compared with WT controls. Administration of Evans blue revealed normal barrier function of the ME–ARH interface and impaired fasting-induced remodeling of the blood–hypothalamic barrier, suggesting an attenuated ability of blood-borne molecules to enter the ARH. Moreover, in 5- and 12-month-old APP/PS1 mice, tanycytes exhibited a similar expression pattern of the zonula occludins-1 (ZO-1) tight-junction complex relative to age-matched control littermates. Interestingly, although random and actual food intake was similar among 5- and 12-month-old APP/PS1 and WT mice, fasting blood glucose and rebound feeding was significantly higher in 12-month-old APP/PS1 mice than WT mice. We also detected more c-Fos immunoreactive neurons in the ARH and more areas of ARH occupied by tanycytic processes in 12-month-old APP/PS1 mice, providing more anatomical evidence for tanycyte–neuron communication in the ARH. These results uncovered changes in morphology and barrier function of tanycytes in APP/PS1 mice, which may be associated with abnormal hypothalamic glucose metabolism.