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

Abstract

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.

Glycogen Synthase Kinase 3β Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites

“…Interestingly, it was demonstrated that progressively weighted ladder climbing as a rodent model of resistance-exercise training (RT) ameliorated LPS(UO)-induced cognitive impairment, a forerunner to neuroinflammatory diseases. These improvements in cognitive function occurred in concert with RT-induced IGF-1R/Akt/GSK3β signaling ( 93 ).…”

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

“…The MCI model is discussed in greater detail elsewhere [ 19 , 23 ] and involves intracerebroventricular (i.c.v.) injections of LPS (Sigma, St. Louis, MO, USA).…”

“…Herein, we utilized an LPS-induced rodent MCI model, which exhibits impaired spatial and recognition memory, published previously by our laboratory [ 19 ], to examine potential cognitive effects of Cr supplementation. Furthermore, we examined neuro-molecular mechanisms in the dentate gyrus resulted from and associated with Cr supplementation, this being a sub-region of hippocampus known to play a fundamental role in hippocampus-dependent learning and memory [ 20 , 21 ].…”

The Effects of High-intensity Functional Training (HIFT) on Spatial Learning, Visual Pattern Separation and Attention Span in Adolescents

“…These pleiotropic factors promote neurogenesis, neuronal survival and neuroplasticity (Pedersen and Febbraio, 2012 ; Jin et al, 2018 ; Lourenco et al, 2019 ; Martínez Muñoz et al, 2019 ), and cognitive abilities (Cotman et al, 2007 ; Lee et al, 2012 ). Several studies have shown that strength training increase BDNF and IGF-1 (Hess and Smart, 2017 ; Kelty et al, 2019 ; Quiles et al, 2019 ; Mckay et al, 2020 ), more so than aerobic exercise in the CNS, shown by studies in rodents, and in the circulation, shown in studies in humans (De Souza Vale et al, 2009 ; Chen et al, 2017 ; Hess and Smart, 2017 ; Kelty et al, 2019 ). Strength training and HIIT were both shown to exert positive effects on various types of cognitive abilities (Cassilhas et al, 2007 ; Tsukamoto et al, 2016 ; Fiorelli et al, 2019 ; Landrigan et al, 2019 ).…”