Oxidative stress and redox regulation on hippocampal-dependent cognitive functions

Abstract

Hippocampal-dependent cognitive functions rely on production of new neurons and maintenance of dendritic structures to provide the synaptic plasticity needed for learning and formation of new memories. Hippocampal formation is exquisitely sensitive to patho-physiological changes, and reduced antioxidant capacity and exposure to low dose irradiation can significantly impede hippocampal-dependent functions of learning and memory by reducing the production of new neurons and alter dendritic structures in the hippocampus. Although the mechanism leading to impaired cognitive functions is complex, persistent oxidative stress likely plays an important role in the SOD-deficient and radiation-exposed hippocampal environment. Aging is associated with increased production of pro-oxidants and accumulation of oxidative end products. Similar to the hippocampal defects observed in SOD-deficient mice and mice exposed to low dose irradiation, reduced capacity in learning and memory, diminishing hippocampal neurogenesis, and altered dendritic network are universal in the aging brains. Given the similarities in cellular and structural changes in the aged, SOD-deficient, and radiation-exposed hippocampal environment and the corresponding changes in cognitive decline, understanding the shared underlying mechanism will provide more flexible and efficient use of SOD deficiency or irradiation to model age-related changes in cognitive functions and identify potential therapeutic or intervention methods.

The impact of aging, hearing loss, and body weight on mouse hippocampal redox state, measured in brain slices using fluorescence imaging

“…The current data add to a growing body of literature demonstrating aging-related increases in mitochondrial dysfunction and that this dysfunction is particularly notable in the hippocampus (El Mohsen, et al, 2005, Huang, et al, 2015, Navarro, et al, 2008, Parihar and Brewer, 2007, Parihar, et al, 2008, Siqueira, et al, 2005). One difference between our work and at least one other study is that the aging-related changes in the current study appear to be driven by a rise in the FAD signal, rather than changes in the NADH signal seen in cultured hippocampal neurons (Parihar, et al, 2008).…”

“…In addition, there have been numerous previous studies demonstrating that the aging brain, particularly the hippocampus, is highly sensitive to metabolic insults (El Mohsen, et al, 2005, Huang, et al, 2015, Navarro, et al, 2008, Parihar, et al, 2008, Siqueira, et al, 2005). Therefore, it is possible that the aging-related differences in the CA2 and CA3 redox state seen in the current study are driven by the metabolic stress induced by the production of brain slices, and may not reflect differences that would be seen in situ in a living organism.…”

Fus1 KO Mouse As a Model of Oxidative Stress-Mediated Sporadic Alzheimer's Disease: Circadian Disruption and Long-Term Spatial and Olfactory Memory Impairments

“…Moreover, deficits in hippocampal learning and memory have been shown to be linked to oxidative stress associated with aging (Huang et al, 2015). ROS have been shown to adversely affect synaptic plasticity (reviewed in Massaad and Klann, 2011).…”

Vulnerability of white matter tracts and cognition to the SOD2 polymorphism: A preliminary study of antioxidant defense genes in brain aging

“…Each of these structures is vulnerable to Alzheimer's pathology, particularly the accumulation of oxidative end products and reduced antioxidant capacity in the hippocampus. Both aging and genetically determined SOD2 deficiencies promote oxidative stress in the hippocampus, thereby leading to reductions in cognitive function [89]. Relatedly, the PCC is a primary connectivity hub for major cortical networks [90], allowing information processing across disparate brain systems.…”