Title:Depression-like Behavior Induced by Repeated Administration of
Dexamethasone to Lipopolysaccharide-inflamed Mice
Volume: 17
Author(s): Fumiya Shibagaki, Naoko Kojima, Akane Furukawa and Noritaka Nakamichi*
Affiliation:
- Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki 370-0033, Japan
Keywords:
Depression, Dexamethasone, Lipopolysaccharide, Hippocampus, Neuroinflammation, Neurotrophic factor, Doublecortin.
Abstract:
Background:
Over the years, animal models of depression have been developed by loading chronic stress, inducing neuroinflammation, or administering drugs
that induce depression; however, these results have poor reproducibility. Therefore, it is necessary to develop animal models that exhibit definitive
symptoms of depression for studies on potential therapeutics.
Objective:
This study was aimed at investigating depression-like symptoms and their pathogenesis in lipopolysaccharide (LPS)-inflamed mice treated with
dexamethasone (DEX).
Methods:
Male ICR mice were injected with LPS, followed by injection with DEX a day later and each day for 6 consecutive days. Depression-like behavior,
expression of the glial markers glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba1), and the number of the
immature neuronal marker doublecortin (DCX)-positive cells were assessed using tail-suspension test (TST), forced swim test (FST), western blot
analysis, and immunohistochemical analysis.
Results:
Mice in the LPS+DEX group had significantly longer immobility time in the TST and FST than did those in the LPS- or DEX-only and control
groups on day 7 post-LPS administration. GFAP and Iba1 expression was significantly elevated in the hippocampus of mice in the LPS group than
in those of mice in the control group. Moreover, a significantly lower number of DCX-positive cells was observed in the hippocampal dentate
gyrus of mice in the LPS+DEX group compared with that in mice in the LPS- or DEX-only and control groups on day 7 after LPS administration.
Conclusion:
Repeated DEX administration to LPS-inflamed mice may induce definitive depression-like symptoms by decreasing the number of immature
neurons in the hippocampal dentate gyrus. This novel mouse model of depression was produced by repeated administration of steroids to inflamed
mice.
