Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

Abstract

The brain is a metabolically active organ exhibiting high oxygen consumption and robust production of reactive oxygen species (ROS). The large amounts of ROS are kept in check by an elaborate network of antioxidants, which sometimes fail and lead to neuronal oxidative stress. Thus, ROS are typically categorized as neurotoxic molecules and typically exert their detrimental effects via oxidation of essential macromolecules such as enzymes and cytoskeletal proteins. Most importantly, excessive ROS are associated with decreased performance in cognitive function. However, at physiological concentrations, ROS are involved in functional changes necessary for synaptic plasticity and hence, for normal cognitive function. The fine line of role reversal of ROS from good molecules to bad molecules is far from being fully understood. This review focuses on identifying the multiple sources of ROS in the mammalian nervous system and on presenting evidence for the critical and essential role of ROS in synaptic plasticity and memory. The review also shows that the inability to restrain either age-or pathology-related increases in ROS levels leads to opposite, detrimental effects that are involved in impairments in synaptic plasticity and memory function.

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…Waking therefore represents a state of higher oxygen, ATP, and glucose consumption, resulting in high rates of metabolic burdens (Everson, Henchen, Szabo, & Hogg, 2014). Therefore, without sufficient NREM sleep, the neurotoxicity and oxidative effects of AD pathophysiology are higher (Everson et al, 2014; Massaad & Klann, 2011; Villafuerte et al, 2015). Furthermore, Aβ accumulation is promoted by oxidative stress (Misonou, Morishima‐Kawashima, & Ihara, 2000) and further promotes oxidative stress itself.…”

SUMO1‐conjugation is altered during normal aging but not by increased amyloid burden

“…Alterations in the proper function of these processes have been implicated in the modulation of memory and synapse plasticity during aging (Cookson, 2012; Narciso et al., 2016). As SUMOylation is a key regulator of gene expression, it will be very exciting to study whether SUMO1 conjugation may play a role in the development or even in the compensation of age‐related cognitive decline via buffering alterations in DNA damage response and RNA processing (Massaad & Klann, 2011). …”

The molecular basis of cognitive deficits in pervasive developmental disorders: Table 1.

“…Third, it may be necessary to shift from intensely focused efforts on a handful of conditions such as RTT, FXS, and AS to PDDs associated with mitochondrial dysfunction because these likely represent a much larger set of afflicted individuals. On a related note, there is a paucity of data examining the role of oxidative stress in social cognition deficits in PDD, which is in contrast to studies of mouse models of aging and neurodegenerative disease (Massaad and Klann 2011). As was discussed earlier, in addition to mitochondrial dysfunction, altered DNA regulation and protein transport appear to play important roles in the manifestation of specific cognitive disruptions in mouse models of PDD, which should provide additional molecular targets for intervention (Sakurai et al 2008).…”