Effects of chronic hypoxia on the expression of seladin-1/Tuj1 and the number of dark neurons of hippocampus

Simin Mahakizadeh; Tahmineh Mokhtari; Fatemeh Navaee; Mahnaz Poorhassan; Armin Tajik; Gholamreza Hassanzadeh

doi:10.1016/j.jchemneu.2020.101744

Effects of chronic hypoxia on the expression of seladin-1/Tuj1 and the number of dark neurons of hippocampus

J Chem Neuroanat. 2020 Jan 9:104:101744. doi: 10.1016/j.jchemneu.2020.101744. Online ahead of print.

Authors

Simin Mahakizadeh¹, Tahmineh Mokhtari², Fatemeh Navaee³, Mahnaz Poorhassan³, Armin Tajik⁴, Gholamreza Hassanzadeh⁵

Affiliations

¹ Department of Anatomy, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
² CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
³ Department of Anatomy, School of Medicine, Shahidbeheshti University of Medical Sciences, Tehran, Iran.
⁴ Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran.
⁵ Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: hassanzadeh@tums.ac.ir.

PMID: 31926979
DOI: 10.1016/j.jchemneu.2020.101744

Abstract

Background: There are evidences showing the relation between chronic hypoxia and Alzheimer's disease (AD) as a metabolic neurodegenerative disease. This study was designed to evaluate the effects of chronic hypoxia on factors which characterized in AD to introduce a new model of AD-dementia.

Methods and materials: Twenty-four male rats were randomly divided in three groups: Control group (Co), Sham group (Sh), Hypoxia induction group (Hx, exposed to hypoxic chamber [oxygen 8% and nitrogen 92%] for 30 days, 4 h/day). Spatial learning and memory were analyzed using the Morris water maze task. At day 30 after hypoxia period, animals were sacrificed and serum was gathered for pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor) measurements and brains were used for molecular and histopathological investigations.

Results: According to behavioral studies, a significant impairment was seen in Hx group (P < 0.05). TNF-α and IL-1β showed a significant enhanced in Hx group comparing with Co group and Sh group (P < 0.05). As well, the gene expression of seladin-1, Tuj1 and the number of seladin-1+, Tuj1+neurons significantly decreased and also the mean number of dark neurons significantly increased in CA1 and CA3 regions of hippocampus.

Conclusions: In this study, a new model of AD was developed which showed the underlying mechanisms of AD and its relations with chronic hypoxia. Hypoxia for 30 days decreased seladin-1, Tuj1 expression, increased the number of dark neurons, and also induced memory impairment. These results indicated that chronic hypoxia mediated the dementia underlying AD and AD-related pathogenesis in rat.

Keywords: Alzheimer’s disease; Dementia; Hypoxia; Inflammation; Memory impairment; seladin-1.