4-Hydroxynonenal Immunoreactivity Is Increased in the Frontal Cortex of 5XFAD Transgenic Mice

Abstract

Oxidative stress was implicated in the functional impairment of the frontal cortex observed in early Alzheimer’s disease (AD). To elucidate this role in an animal AD model, we assessed cognitive function of 4-month-old five familial AD (5XFAD) transgenic (Tg) mice using a learning strategy-switching task requiring recruitment of the frontal cortex and measuring levels of 4-hydroxy-2-trans-nonenal (4-HNE), a marker of oxidative stress, in their frontal cortex. Mice were sequentially trained in cued/response and place/spatial versions of the water maze task for four days each. 5XFAD and non-Tg mice exhibited equal performance in cued/response training. However, 5XFAD mice used spatial search strategy less than non-Tg mice in the spatial/place training. Immunoblot and immunofluorescence staining showed that 4-HNE levels increased in the frontal cortex, but not in the hippocampus and striatum, of 5XFAD mice compared to those in non-Tg mice. We report early cognitive deficits related to the frontal cortex and the frontal cortex’s oxidative damage in 4-month-old 5XFAD mice. These results suggest that 4-month-old 5XFAD mice be a useful animal model for the early diagnosis and management of AD.

Improvement of retinal function in Alzheimer disease-associated retinopathy by dietary lysophosphatidylcholine-EPA/DHA

“…It is likely that the depletion DHA by congenital deficiency of Mfsd2a is not comparable to DHA deficiency achieved by dietary manipulation or due to oxidative stress. While the expression of Mfsd2a, as well as its protein levels have been reported to be normal in 5XFAD mice 48 , there is strong evidence for increased oxidative stress in 5XFAD mice 49 , 50 , which could lead to loss of retinal DHA.…”

Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases

“…These signs are commonly exhibited in patients with this neuropathology [41]. High levels of biomarkers of oxidative stress in blood plasma and urine have been found in both animal models [42][43][44][45][46][47] and patients with Alzheimer's disease [48][49][50][51], which correlates with the aggregation and deposits of β-amyloid. In addition, a proteomic study has shown that the higher risk of developing neurodegenerative disorders in patients with Down syndrome can be explained by their higher susceptibility to damage caused by oxidative stress [52].…”

“…One of the main causes of this phenomenon, oxidative stress, affects a number of metabolic pathways [40], and evidence of the involvement of free radicals in cognitive impairment has been obtained from patients suffering from neurodegeneration. In Alzheimer's disease, redox-mediated damage to various biomolecules has often been reported [41][42][43][44][45][46][47][48][49][50][51][52]. Thus, in the search for the mechanisms underlying this disorder, in addition to the dominant hypothesis of the amyloid cascade, an alternative explanation for the pathogenesis of this disease was proposed, which consisted of the relationship between mitochondrial dysfunction and the hyperproduction of reactive oxygen species.…”

Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases

“…Lipid peroxidation products formed during iron death lead to increased metabolites downstream of the AD brain, including 4-HNE, MDA, and acrolein. It was shown that elevated 4-HNE content in the brains of people with AD causes damaging carbonylation of proteins reactions (Lovell et al, 1997 ; Jaganjac et al, 2020 ; Shin et al, 2020 ). Further research has demonstrated that 4-HNE binds to Aβ polypeptides to form covalent complexes, promoting covalent cross-linking of Aβ polypeptides and protofibril formation (Siegel et al, 2007 ).…”