Running from Stress: Neurobiological Mechanisms of Exercise-Induced Stress Resilience

Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged to be a predisposing or precipitating factor in neuropsychiatric diseases. There is a clear relationship between disturbances induced by stressful stimuli, especially long-lasting stimuli, and cognitive deficits in rodent models of affective disorders. Regular physical activity has a positive effect on the central nervous system (CNS) functions, contributes to an improvement in mood and of cognitive abilities (including memory and learning), and is correlated with an increase in the expression of the neurotrophic factors and markers of synaptic plasticity as well as a reduction in the inflammatory factors. Studies published so far show that the energy challenge caused by physical exercise can affect the CNS by improving cellular bioenergetics, stimulating the processes responsible for the removal of damaged organelles and molecules, and attenuating inflammation processes. Regular physical activity brings another important benefit: increased stress robustness. The evidence from animal studies is that a sedentary lifestyle is associated with stress vulnerability, whereas a physically active lifestyle is associated with stress resilience. Here, we have performed a comprehensive PubMed Search Strategy for accomplishing an exhaustive literature review. In this review, we discuss the findings from experimental studies on the molecular and neurobiological mechanisms underlying the impact of exercise on brain resilience. A thorough understanding of the mechanisms underlying the neuroprotective potential of preconditioning exercise and of the role of exercise in stress resilience, among other things, may open further options for prevention and therapy in the treatment of CNS diseases

Global Proteome Profiling of the Temporal Cortex of Female Rats Exposed to Chronic Stress and the Western Diet

The increasing consumption of highly processed foods with high amounts of saturated fatty acids and simple carbohydrates is a major contributor to the burden of overweight and obesity. Additionally, an unhealthy diet in combination with chronic stress exposure is known to be associated with the increased prevalence of central nervous system diseases. In the present study, the global brain proteome approach was applied to explore protein alterations after exposure to the Western diet and/or stress. Female adult rats were fed with the Western diet with human snacks and/or subjected to chronic stress induced by social instability for 12 weeks. The consumption of the Western diet resulted in an obese phenotype and induced changes in the serum metabolic parameters. Consuming the Western diet resulted in changes in only 5.4% of the proteins, whereas 48% of all detected proteins were affected by chronic stress, of which 86.3% were down-regulated due to this exposure to chronic stress. However, feeding with a particular diet modified stress-induced changes in the brain proteome. The down-regulation of proteins involved in axonogenesis and mediating the synaptic clustering of AMPA glutamate receptors (Nptx1), as well as proteins related to metabolic processes (Atp5i, Mrps36, Ndufb4), were identified, while increased expression was detected for proteins involved in the development and differentiation of the CNS (Basp1, Cend1), response to stress, learning and memory (Prrt2), and modulation of synaptic transmission (Ncam1, Prrt2). In summary, global proteome analysis provides information about the impact of the combination of the Western diet and stress exposure on cerebrocortical protein alterations and yields insight into the underlying mechanisms and pathways involved in functional and morphological brain alterations as well as behavioral disturbances described in the literature

Effects of Simultaneous Exposure to a Western Diet and Wheel-Running Training on Brain Energy Metabolism in Female Rats

Background: In the pathogenesis of central nervous system disorders (e.g., neurodegenerative), an important role is attributed to an unhealthy lifestyle affecting brain energy metabolism. Physical activity in the prevention and treatment of lifestyle-related diseases is getting increasing attention. Methods: We performed a series of assessments in adult female Long Evans rats subjected to 6 weeks of Western diet feeding and wheel-running training. A control group of lean rats was fed with a standard diet. In all experimental groups, we measured physiological parameters (animal weights, body composition, serum metabolic parameters). We assessed the impact of simultaneous exposure to a Western diet and wheel-running on the cerebrocortical protein expression (global proteomic profiling), and in the second part of the experiment, we measured the cortical levels of protein related to brain metabolism (Western blot). Results: Western diet led to an obese phenotype and induced changes in the serum metabolic parameters. Wheel-running did not reduce animal weights or fat mass but significantly decreased serum glucose level. The global proteome analysis revealed that the altered proteins were functionally annotated as they were involved mostly in metabolic pathways. Western blot analysis showed the downregulation of the mitochondrial protein—Acyl-CoA dehydrogenase family member 9, hexokinase 1 (HK1)—enzyme involved in principal glucose metabolism pathways and monocarboxylate transporter 2 (MCT2). Wheel-running reversed this decline in the cortical levels of HK1 and MCT2. Conclusion: The cerebrocortical proteome is affected by a combination of physical activity and Western diet in female rats. An analysis of the cortical proteins involved in brain energy metabolism provides a valuable basis for the deeper investigation of changes in the brain structure and function induced by simultaneous exposure to a Western diet and physical activity