Unexpected Improvements of Spatial Learning and Memory Abilities in Chronic Rotenone Intoxicated Mice

Fengju Jia,Ning Song,Hong Jiang,Chenyang Zhao,Junxia Xie,Christian Holscher

doi:10.1371/journal.pone.0091641

Abstract

The liposoluble insecticide rotenone is commonly used as a mitochondrial complex I inhibitor to replicate Parkinson's disease (PD) pathological features. However, there was no assessment of the spatial learning and memory abilities in chronic rotenone-induced PD models. In the present study, by rotarod test and Thioflavine T staining, we first noted the impairment of motor coordination in rotenone-treated group for 3 months, as well as alpha-synuclein inclusions in the nigral dopaminergic neurons in C57BL/6 mice with intragastrical delivery of rotenone (5 mg/Kg) for 3 months rather than 1 month. We then evaluated spatial learning and memory abilities by Morris water maze task in this model. The results showed escape latency reduced in rotenone-intoxicated mice for 3 months, indicating an improvement of learning ability. However, it was delayed slightly but not significantly in rotenone-intoxicated mice for 1 month. Similarly, we demonstrated that spatial memory ability was enhanced in 3-month-treatment group, but impaired in 1-month-treatment group. There were no proliferating cell nuclear antigen and doublecortin positive cells in the hippocampus by double immunofluorescent staining, indicating the absence of hippocampal neurogenesis in rotenone-intoxicated mice. These results suggest that spatial learning and memory abilities are disturbed in chronic rotenone-intoxicated PD model.

Highlights

Parkinson’s disease (PD), as the second most prevalent neurodegenerative disease, affects as many as 1–2% of the worldwide population over 60 [1,2,3]
We found that the residence time on rotarod treadmills was shorter in 3-monthtreated group, whereas there was no change in 1-month-treated group (Figure 1)
These results indicated that motor coordination ability was impaired in mice with intragastrical rotenone administration for 3 months

Summary

Introduction

Parkinson’s disease (PD), as the second most prevalent neurodegenerative disease, affects as many as 1–2% of the worldwide population over 60 [1,2,3]. It is characterized by selective loss of the dopaminergic neurons in the substantia nigra pars compacta (SNpc), a profound loss of dopamine (DA) in the striatum, and the presence of intracytoplasmic inclusions called Lewy bodies (LB) in the remaining dopaminergic neurons [4,5,6]. A high rate as 84% in cognitive decline was reported in one long-term (15–18 years) follow-up study of PD patients [11]. We aimed to evaluate changes of spatial learning and memory abilities in chronic PD models by employing an intragastrical model of rotenone intoxication for 1 or 3 months

Objectives

Methods

Results

Conclusion