Is Oxidative Stress the Link Between Cerebral Small Vessel Disease, Sleep Disruption, and Oligodendrocyte Dysfunction in the Onset of Alzheimer’s Disease?

Abstract

Oxidative stress is an early occurrence in the development of Alzheimer’s disease (AD) and one of its proposed etiologic hypotheses. There is sufficient experimental evidence supporting the theory that impaired antioxidant enzymatic activity and increased formation of reactive oxygen species (ROS) take place in this disease. However, the antioxidant treatments fail to stop its advancement. Its multifactorial condition and the diverse toxicological cascades that can be initiated by ROS could possibly explain this failure. Recently, it has been suggested that cerebral small vessel disease (CSVD) contributes to the onset of AD. Oxidative stress is a central hallmark of CSVD and is depicted as an early causative factor. Moreover, data from various epidemiological and clinicopathological studies have indicated a relationship between CSVD and AD where endothelial cells are a source of oxidative stress. These cells are also closely related to oligodendrocytes, which are, in particular, sensitive to oxidation and lead to myelination being compromised. The sleep/wake cycle is another important control in the proliferation, migration, and differentiation of oligodendrocytes, and sleep loss reduces myelin thickness. Moreover, sleep plays a crucial role in resistance against CSVD, and poor sleep quality increases the silent markers of this vascular disease. Sleep disruption is another early occurrence in AD and is related to an increase in oxidative stress. In this study, the relationship between CSVD, oligodendrocyte dysfunction, and sleep disorders is discussed while focusing on oxidative stress as a common occurrence and its possible role in the onset of AD.

Accelerated amyloid angiopathy and related vascular alterations in a mixed murine model of Alzheimer´s disease and type two diabetes

“…Thus, increased levels of reactive oxygen species lead to alterations in blood flow resistance and endothelial regulatory response is impaired by the disruption of endothelium-dependent nitric oxide signaling [ 66 – 68 ], resulting in increased microvessel permeability and impaired microvascular endothelial function [ 67 , 69 – 71 ]. Hydrogen peroxide, superoxide derivates, hydroxyl radical or peroxynitrites increase endothelial calcium concentration in time- and dose-dependent manner causing dysregulation in calcium homeostasis, acting as proapoptotic factor in cerebral vascular cells [ 66 , 70 , 72 ]. In addition, oxidative stress has a key role in insulin resistance and progression of diabetes [ 73 , 74 ] and diabetic mice show vascular alterations associated with increased oxidative stress, pericyte dysfunction and cerebrovascular integrity compromise [ 75 ].…”

Pinus halepensis Essential Oil Ameliorates Aβ1-42-Induced Brain Injury by Diminishing Anxiety, Oxidative Stress, and Neuroinflammation in Rats

“…The brain, generally presenting very low antioxidant levels, is particularly susceptible to oxidative damage [ 114 ]. In AD, brain regions such as the prefrontal cortex, hippocampus, and amygdala are more vulnerable to oxidative damage, dendritic shrinking, and amygdala hyperactivity specifically triggered by oxidative stress [ 115 ]. In the present study, on the amygdala level, it was observed that single-dose administration of Aβ1-42 efficiently induced oxidative state-like changes, such as elevated protein oxidation ( p = 0.0084) ( Figure 6 E) and lipid peroxidation ( p = 0.0084) ( Figure 6 F) rates, as well as a reduced level of GSH ( p = 0.0103) ( Figure 6 D) and decreased activity of antioxidant enzymes CAT ( p = 0.0027) ( Figure 6 A), SOD ( p = 0.0066) ( Figure 6 B), and GPX ( p = 0.0027) ( Figure 6 C).…”

Particulate matter exposure and chronic cerebral hypoperfusion promote oxidative stress and induce neuronal and oligodendrocyte apoptosis in male mice

“…High levels of oxidative stress may induce OPC death, but sublethal levels can disrupt OPC differentiation (Lloret et al, 2021; Miyamoto et al, 2013; Spaas et al, 2021). In‐vitro, ROS exposure altered the expression of oligodendrocyte differentiation regulators, increasing the expression of inhibitors and reducing the expression of positive regulators (French et al, 2009; Lim et al, 2016; Spaas et al, 2021).…”