Contribution of p38 MAPK to the Ameliorating Effect of Enriched Environment on the Cognitive Deficits Induced by Chronic Cerebral Hypoperfusion

Abstract

Background/Aims: An enriched environment (EE) ameliorates learning and memory impairments induced by chronic cerebral hypoperfusion, and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway exerts both beneficial and deleterious effects on the nervous system during the progression of ischemia. Methods: The present study investigated whether p38 MAPK participates in the process by which EE exposure ameliorates the cognitive deficits induced by chronic cerebral hypoperfusion. Results: EE exposure significantly enhanced the cognitive performance of vascular dementia (VD) model rats, and p38 MAPK protein decreased in parallel with cognitive improvements. Inhibition of p38 MAPK function by its selective inhibitor SB203580 improved the cognition index of VD rats and upregulated p38 MAPK expression with p38 MAPK antisense oligodeoxynucleotides. This impaired cognition in VD rats could not be rescued by EE exposure. Conclusion: p38 MAPK participates in the process by which EE exposure ameliorates cognitive deficits induced by chronic cerebral hypoperfusion.

Olfactory Bulb Proteomics Reveals Widespread Proteostatic Disturbances in Mixed Dementia and Guides for Potential Serum Biomarkers to Discriminate Alzheimer Disease and Mixed Dementia Phenotypes

“…As shown in Figure 6C and supplementary Figure 3, both activated and total levels of P38 were upregulated but only in Braak VI stages, suggesting a neuroinflammatory environment at the level of the OB. In line with this findings, recent studies have shown that the activation of this pathway may lead neuronal apoptosis and functional deficits in vascular dementia [57]. In accordance, stage-specific alterations were also found for both activated and total levels of SEK1, again demonstrating altered cell-stress responses at olfactory level during MixD disorders.…”

Treatment with Enriched Environment Reduces Neuronal Apoptosis in the Periinfarct Cortex after Cerebral Ischemia/Reperfusion Injury

“…Mounting studies have suggested that exposure to EE treatment after brain injury leads to neuroprotective effects in animal models [9, 10]. Recently, EE treatment has been translated into a rehabilitation strategy for poststroke patients in the clinical setting [11].…”

Enriched environment alleviates post-stroke cognitive impairment through enhancing α7-nAChR expression in rats

“…Enriched environment (EE) is an effective rodent rehabilitation treatment method, in which several animals are accommodated in a large space equipped with various toys and receive more sensorial movements, perceptions and social stimulation than in standard conditions. EE has a neuroprotective effect on animal models of cerebral ischemia 4 . There is significant evidence that EE also benefits the clinical rehabilitation of post-stroke patients, including promoting greater exercise, social interaction and personal control 5 .…”