Abstract
[Purpose]Chronic stress is a risk factor for behavioral deficits, including impaired memory processing and depression. Exercise is well known to have beneficial impacts on brain health. [Methods]Mice were forced to treadmill running (4-week) during chronic restraint stress (6h/21d), and then behavioral tests were conducted by Novel object recognition, forced swimming test: FST, sociality test: SI. Dissected brain was stained with anti-calbindin-d28k and anti-Arc antibodies. Also, mice were treated with CX546 intraperitoneally during chronic restraint stress, and behavioral tests were assessed using Morris water maze, FST, and SI. Dissected brain was stained with anti-Arc antibody. [Results]The current study demonstrated that chronic stress-induced impairment of memory consolidation and depression-like behaviors, along with the changes in calbindin-d28k and Arc protein levels in the hippocampal CA1 area, were attenuated by regular treadmill running. Further, prolonged ampakine treatment prevented chronic stress-evoked behavioral abnormalities and nuclear Arc levels in hippocampal CA1 neurons. Nuclear localization of Arc protein in hippocampal CA1 neurons, but not total levels, was correlated with behavioral outcome in chronically stressed mice in response to a regular exercise regimen. [Conclusion]These results suggest that nuclear levels of Arc are strongly associated with behavioral changes, and highlight the role of exercise acting through an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR)-mediated mechanisms in a chronic stress-induced maladaptive condition.
Highlights
Chronic stress is a potent predictor for the development of memory processing impairments and psychiatric defects, including longterm memory impairments and depression
We found that chronic stress (6h/21d) induced a decrease in the exploration ratio of the novel object, a decrease in Social interaction (SI) index, and an increase in immobility during the forced swimming test (FST), which was reversed by regular exercise (Fig. 1AB; for the exploration ratio: CON t12 = -2.56, p 0.05; RST+Ex t14 = -2.67, p < 0.05; Ex t12 = -2.79, p < 0.05; for SI: F3, 26 = 3.03, p < 0.05; for immobility: F3, 26 = 4.13)
The current study demonstrated that regular exercise exerted protective effects against chronic stress-induced behavioral deficits, including the impairment of longterm memory formation and the development of depressive symptoms, likely by reducing AMPAR-mediated excitatory responsiveness in hippocampal CA1 cells
Summary
Chronic stress is a potent predictor for the development of memory processing impairments and psychiatric defects, including longterm memory impairments and depression. Chronic stress-evoked abnormalities in activity-dependent synaptic plasticity are strongly associated with these neuropathophysiological conditions 1. The activity-regulated cytoskeletal gene Arc, known as Arg3.1, plays a critical role in synaptic strength and plasticity during memory consolidation. Translation, localization, and stability are tightly controlled by neuronal activity 2, suggesting various functions depending on its particular characteristics. Arc plays a pivotal role in long-term potentiation (LTP) by regulating cytoskeletal dynamics and spine morphology, as well as in long-term depression (LTD) by mediating metabotropic glutamate receptor (mGluR)-induced LTD via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) endocytosis at synapses [3,4]. Several studies have demonstrated that Arc expression mostly increases in response to acute stress in the prefrontal cortex, with an AMPAR and N-methyl-D-aspartate (NMDA) receptor (NMDAR)-dependent increase in glutamatergic neurotransmission [5,6]. Translated Arc protein translocates into the nucleus, and contributes to GluR1 expression and synaptic plasticity in stimulated neurons, in in vivo and in vitro experiments [10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
