TY - JOUR
T1 - Treadmill exercise restores high fat diet-induced disturbance of hippocampal neurogenesis through β2-adrenergic receptor-dependent induction of thioredoxin-1 and brain-derived neurotrophic factor
AU - Han, Tae Kyung
AU - Leem, Yea Hyun
AU - Kim, Hee Sun
N1 - Funding Information:
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government ( MSIT ) ( 2010-0027945 ).
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/3/15
Y1 - 2019/3/15
N2 - A high-fat diet (HFD) is known to induce metabolic disturbances that may lead to cognitive impairment. In the present study, we investigated whether a regular treadmill exercise program would improve HFD-induced hippocampal-dependent memory deficits in C57BL/6 mice. Weight gain and hepatic triglyceride levels were profoundly elevated following administration of a 60% HFD for 23 weeks, and this change was attenuated by 23-weeks of treadmill running. The exercise regimen attenuated impairments in memory function of HFD-fed mice in a water maze test and recovered HFD-induced anti-neurogenic effects as shown by immunohistochemistry data with Ki-67 and doublecortin (DCX) antibodies. Moreover, the treadmill exercise resulted in anti-inflammatory, antioxidant, and neuroprotective effects in the HFD-fed brain. The exercise inhibited HFD-induced microglial activation, expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and NF-κB activity in the dentate gyrus (DG) of the hippocampus. In addition, the exercise reduced malondialdehyde levels elevated by HFD and recovered antioxidant superoxide dismutase and glutathione levels in hippocampal DG of HFD-mice. The exercise also reduced the number of apoptotic cells induced by HFD, as shown by TUNEL staining in the DG region. Finally, we demonstrated that the thioredoxin-1 (TRX-1) and brain-derived neurotrophic factor (BDNF) levels were recovered by exercise, which was demonstrated to act via β2-adrenergic receptor enriched in synaptosomes of the DG. Therefore, our data collectively suggests that regular exercise may be a promising approach to preventing HFD-induced memory impairments via anti-inflammatory, antioxidant and neuroprotective mechanisms in the hippocampal DG region.
AB - A high-fat diet (HFD) is known to induce metabolic disturbances that may lead to cognitive impairment. In the present study, we investigated whether a regular treadmill exercise program would improve HFD-induced hippocampal-dependent memory deficits in C57BL/6 mice. Weight gain and hepatic triglyceride levels were profoundly elevated following administration of a 60% HFD for 23 weeks, and this change was attenuated by 23-weeks of treadmill running. The exercise regimen attenuated impairments in memory function of HFD-fed mice in a water maze test and recovered HFD-induced anti-neurogenic effects as shown by immunohistochemistry data with Ki-67 and doublecortin (DCX) antibodies. Moreover, the treadmill exercise resulted in anti-inflammatory, antioxidant, and neuroprotective effects in the HFD-fed brain. The exercise inhibited HFD-induced microglial activation, expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and NF-κB activity in the dentate gyrus (DG) of the hippocampus. In addition, the exercise reduced malondialdehyde levels elevated by HFD and recovered antioxidant superoxide dismutase and glutathione levels in hippocampal DG of HFD-mice. The exercise also reduced the number of apoptotic cells induced by HFD, as shown by TUNEL staining in the DG region. Finally, we demonstrated that the thioredoxin-1 (TRX-1) and brain-derived neurotrophic factor (BDNF) levels were recovered by exercise, which was demonstrated to act via β2-adrenergic receptor enriched in synaptosomes of the DG. Therefore, our data collectively suggests that regular exercise may be a promising approach to preventing HFD-induced memory impairments via anti-inflammatory, antioxidant and neuroprotective mechanisms in the hippocampal DG region.
KW - High-fat diet
KW - Hippocampal neurogenesis
KW - Neuroinflammation
KW - Regular exercise
KW - Thioredoxin-1
KW - β2-Adrenergic receptor
UR - http://www.scopus.com/inward/record.url?scp=85057320389&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2018.11.035
DO - 10.1016/j.brainres.2018.11.035
M3 - Article
C2 - 30496734
AN - SCOPUS:85057320389
VL - 1707
SP - 154
EP - 163
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -