Resistance-exercise training attenuates LPS-induced astrocyte remodeling and neuroinflammatory cytokine expression in female Wistar rats

2021 ◽  
Author(s):  
Taylor J. Kelty ◽  
Xuansong Mao ◽  
Nathan R. Kerr ◽  
Thomas E. Childs ◽  
Gregory N. Ruegsegger ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Exercise Training ◽  
Resistance Exercise ◽  
Dentate Gyrus ◽  
Wistar Rats ◽  
Cytokine Expression ◽  
Resistance Exercise Training ◽  
Female Wistar Rats ◽  
Underlying Mechanisms

Neuroinflammation is an early detectable marker of mild cognitive impairment, the transition state between normal cognition and dementia. Resistance-exercise training can attenuate the cognitive decline observed in patients with mild cognitive impairment. However, the underlying mechanisms of resistance training effects are largely unknown. To further elucidate mechanisms of the known cognitive health benefits from resistance-exercise training, we tested if three weeks of resistance-exercise training could ameliorate lipopolysaccharide-induced neuroinflammation. Five-week-old female Wistar rats received intracerebroventricular injections of lipopolysaccharides to induce neuroinflammation and cognitive impairment. Rats then underwent three weeks of progressive ladder climbing to recapitulate resistance-exercise training in humans. Cognition was assessed towards the end of the training period by novelty object recognition testing. Neuroinflammation was measured one and 24-hours after the last resistance-exercise training workout. Resistance-exercise training ameliorated cognitive impairment, diminished lipopolysaccharide-induced neuroinflammatory cytokine expression, and attenuated astrocyte remodeling in the dentate gyrus 24-hours post exercise. Here, we provide evidence that the ladder-climbing model of resistance-exercise training in rats can improve cognition as early as three weeks. Additionally, these data support the hypothesis that resistance exercise can reduce lipopolysaccharide-induced neuroinflammation in the dentate gyrus.

scholarly journals The role of resistance exercise training and IGF-1 signaling in the amelioration of mild cognitive impairment in female Wistar rats

2021 ◽  
Author(s):  
◽  
Taylor Jacob Kelty
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Exercise Training ◽  
Resistance Exercise ◽  
Dentate Gyrus ◽  
Wistar Rats ◽  
Molecular Mechanisms ◽  
Preclinical Model ◽  
Resistance Exercise Training ◽  
Female Wistar Rats

Mild cognitive impairment increases risk for dementia. One therapeutic intervention that is reported to ameliorate cognition in patients with mild cognitive impairment is resistance exercise. However, the underlying neuro-molecular mechanisms behind resistance exercise are largely unknown. To better understand the underlying neuro-molecular mechanisms, I established a preclinical model of resistance-exercise training and mild cognitive impairment based off the literature. Ladder climbing in female Wistar rats let to similar increases in muscle mass and strength as those observed in humans, while intracerebroventricular injections of lipopolysaccharides (LPS) induced neuroinflammation and cognitive deficits, which resembled clinical mild cognitive impairment. Resistance-exercise training restored cognitive function, increased IGF-1R phosphorylation and subsequent downstream signaling, and ameliorated neuroinflammation. Selective IGF-1R inhibition in the dentate gyrus, with picropodophyllin, had differential effects on cognition dependent on training status and type of cognition measured. Collectively, these studies indicate that although resistance training and IGF-1 signaling both ameliorate LPS-induced neuroinflammation, IGF-1 signaling during resistance-exercise training, but is only necessary for its ability to ameliorate mild cognitive impairment after a single workout. Furthermore, we made a novel discovery where dentate gyrus IGF-1R inhibition can improve specific forms of cognition. These findings reveal the complexity of IGF-1 signaling and open new areas of study that could offer insights for the treatment of mild cognitive impairment.

scholarly journals Resistance-exercise training ameliorates LPS-induced cognitive impairment concurrent with molecular signaling changes in the rat dentate gyrus

2019 ◽  
Vol 127 (1) ◽  
pp. 254-263 ◽  
Author(s):  
Taylor J. Kelty ◽  
Todd R. Schachtman ◽  
Xuansong Mao ◽  
Kolter B. Grigsby ◽  
Thomas E. Childs ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Exercise Training ◽  
Resistance Exercise ◽  
Dentate Gyrus ◽  
Young Female ◽  
Proliferation Marker ◽  
Molecular Signaling ◽  
Resistance Exercise Training ◽  
Downstream Signaling ◽  
Gsk 3Β

Effective treatments preventing brain neuroinflammatory diseases are lacking. Resistance-exercise training (RT) ameliorates mild cognitive impairment (MCI), a forerunner to neuroinflammatory diseases. However, few studies have addressed the molecular basis by which RT abates MCI. Thus experiments were performed to identify some molecular changes occurring in response to RT in young, female Wistar rats. To induce MCI, intraventricular lipopolysaccharide (LPS) injections were used to increase dentate gyrus inflammation, reflected by significantly increased TNF-α (~400%) and IL-1β (~1,500%) mRNA ( P < 0.0001) after 6 wk. Five days after LPS injections, half of LPS-injected rats performed RT by ladder climbing for 6 wk, 3 days/wk, whereas half remained without ladders. RT for 6 wk increased lean body mass percentage ( P < 0.05), individual muscle masses (gastrocnemius and tibialis anterior) ( P < 0.05), and maximum lifting capacity ( P < 0.001). The RT group, compared with sedentary controls, had 1) ameliorated spatial learning deficits ( P < 0.05), 2) increased dentate gyrus phosphorylation of IGF-1R, protein kinase B, and GSK-3β proteins ( P < 0.05), components of downstream IGF-1 signaling, and 3) increased dentate gyrus synaptic plasticity marker synapsin protein ( P < 0.05). Two follow-up experiments (without LPS) characterized dentate gyrus signaling during short-term RT. Twenty-four hours following the third workout in a 1-wk training duration, phosphorylation of ERK1/2 and GSK-3β proteins, as well as proliferation marker protein, PCNA, were significantly increased ( P < 0.05). Similar changes did not occur in a separate group of rats following a single RT workout. Taken together, these data indicate that RT ameliorates LPS-induced MCI after RT, possibly mediated by increased IGF-1 signaling pathway components within the dentate gyrus.NEW & NOTEWORTHY The data suggest that resistance-exercise training restores cognitive deficits induced by lipopolysaccharides and can activate associated IGF-1 signaling in the dentate gyrus. Our data show, for the first time, that as few as three resistance-exercise workouts (spread over 1 wk) can activate IGF-1 downstream signaling and increase proliferation marker PCNA in the dentate gyrus.

scholarly journals Creatine Supplementation Upregulates mTORC1 Signaling and Markers of Synaptic Plasticity in the Dentate Gyrus While Ameliorating LPS-Induced Cognitive Impairment in Female Rats

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2758
Author(s):  
Xuansong Mao ◽  
Taylor J. Kelty ◽  
Nathan R. Kerr ◽  
Thomas E. Childs ◽  
Michael D. Roberts ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Recognition Memory ◽  
Dentate Gyrus ◽  
Wistar Rats ◽  
Young Female ◽  
Memory Deficit ◽  
Female Rats ◽  
Therapeutic Window ◽  
Mtorc1 Signaling ◽  
Female Wistar Rats

Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing. We also investigated both neurocognitive and neuromolecular changes following Cr supplementation in the absence of LPS in young female Wistar rats to further investigate mechanisms. Interestingly, based on trial 2 of Barnes maze test, Cr supplementation ameliorated spatial learning and memory deficit induced by LPS, shown by decreased latency time and errors to reach the escape box (p < 0.0001, n = 12). Cr supplementation also attenuated recognition memory deficit induced by LPS, shown by increased amount of time taken to explore the new object (p = 0.002, n = 12) during novel object recognition testing. Within the dentate gyrus, Cr supplementation in LPS injected rats upregulated mTORC1 signaling (p = 0.026 for mTOR phosphorylation, p = 0.002 for p70S6K phosphorylation, n = 8) as well as the synapsin (p = 0.008) and PSD-95 synaptic proteins (p = 0.015), in comparisons to LPS injected rats. However, Cr supplementation failed to further enhance spatial memory and recognition memory in the absence of LPS. In conclusion, Cr ameliorates LPS-induced cognitive impairment in a rodent MCI model. Mechanistically, these phenotypic effects may, in part, be mitigated via an upregulation of mTORC1 signaling, and an enhancement in synaptogenesis in the dentate gyrus. While preliminary, these findings may inform future research investigating neurocognitive effects of Cr for MCI patients.

scholarly journals Type 2 Diabetes Reduces the Muscle Anabolic Effect of Resistance Exercise Training in Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 529-529
Author(s):  
Amanda Randolph ◽  
Tatiana Moro ◽  
Adetutu Odejimi ◽  
Blake Rasmussen ◽  
Elena Volpi
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Muscle Strength ◽  
Exercise Training ◽  
Resistance Exercise ◽  
Lean Mass ◽  
Synthesis Rate ◽  
Resistance Exercise Training ◽  
Appendicular Lean Mass

Abstract Type 2 Diabetes Mellitus (T2DM) accelerates the incidence and increases the prevalence of sarcopenia in older adults. This suggests an urgent need for identifying effective sarcopenia treatments for older adults with T2DM. It is unknown whether traditional approaches, such as progressive resistance exercise training (PRET), can effectively counteract sarcopenia in older patients with T2DM. To test the efficacy of PRET for the treatment of sarcopenia in older adults with T2DM, 30 subjects (15 T2DM and 15 age- and sex- matched controls) underwent metabolic testing with muscle biopsies before and after a 13-week full-body PRET program. Primary outcome measures included changes in appendicular lean mass, muscle strength, and mixed muscle fractional synthesis rate (FSR). Before PRET, BMI-adjusted appendicular lean mass was significantly lower in the T2DM group (0.7095±0.0381 versus 0.8151±0.0439, p&lt;0.0001). As a result of PRET, appendicular lean mass adjusted for BMI and muscle strength increased significantly in both groups, but to a lesser extent for the T2DM group (p=0.0009) . Preliminary results for FSR (n=25) indicate that subjects with T2DM had lower basal FSR prior to PRET (p=0.0197) . Basal FSR increased significantly in the control group after PRET (p=0.0196), while it did not change in the T2DM group (p=0.3537). These results suggest that in older adults the positive effect of PRET on muscle anabolism and strength is reduced by T2DM . Thus, older adults with T2DM may require more intensive, multimodal and targeted sarcopenia treatment. Funded by NIH R01AG049611 and P30AG024832.

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