Immunohistochemical analysis of tau phosphorylation and astroglial activation with enhanced leptin receptor expression in diet-induced obesity mouse hippocampus

• Published in: Neuroscience letters 2014-06, Vol.571, p.11-16
• Main Authors: Koga, Shunsuke, Kojima, Ayako, Kuwabara, Satoshi, Yoshiyama, Yasumasa
• Format: Article
• Language: English
• Subjects: Alzheimer disease; Animals; Astrocyte; Astrocytes - pathology; Diet-induced obesity; Dietary Fats; Female; Gliosis; Hippocampus - metabolism; Mice; Obesity - etiology; Obesity - metabolism; Obesity - pathology; Phosphorylation; Physical Conditioning, Animal; Receptors, Leptin - metabolism; Tau phosphorylation; tau Proteins - metabolism; Voluntary exercise; Weight Gain; Wild-type mouse
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2014.04.028

•Diet-induced obesity (DIO) causes tau phosphorylation in wild-type mouse hippocampus.•DIO enhances astrogliosis, astroglial leptin receptor expression, and mild microgliosis.•Astroglial leptin receptor may play a role in these pathological processes.•Voluntary exercise can prevent these DIO-induced pathological changes. Accumulating evidence indicates that obesity is an independent risk factor for developing Alzheimer disease (AD). Recent studies have shown that diet-induced obesity (DIO) enhances AD-related pathologies in transgenic mouse models of the disease. DIO increases amyloid β (Aβ) deposition in amyloidogenic transgenic mice and enhances tau phosphorylation in tau transgenic mice. However, it remains unclear whether DIO also enhances AD-related pathological processes in wild-type (WT) mice. In this study, we examined the effects of DIO on Aβ and tau pathology in WT mice using immunohistochemistry. In addition, we evaluated the protective effect of voluntary exercise on the DIO-induced pathological changes. DIO caused tau phosphorylation and astroglial activation in the hippocampus in WT mice. Interestingly, these changes were associated with enhanced astrocytic leptin receptor (LepR) expression and mild microgliosis, but not Aβ accumulation. Although phosphorylated tau staining was only observed in the hippocampus, astrogliosis and microgliosis were present in both the amygdala and hippocampus. However, no apparent neuronal loss was observed. Voluntary exercise prevented these DIO-induced pathological changes. Our results demonstrate for the first time that DIO causes tau phosphorylation and that astrocytic LepR might be involved in the pathological process in WT mouse hippocampus. Our findings also suggest that physical exercise is a promising strategy for the prevention of AD in patients with obesity.