Homocysteine induces τ hyperphosphorylation in rats

Abstract

Epidemiological and clinical data suggest that homocysteine (Hcy) may increase the risk of Alzheimer's disease, but the underlying mechanisms are elusive. To investigate the effect of Hcy on phosphorylation of tau, we injected Hcy into the lateral cerebral ventricle of rats. We found that level of the hyperphosphorylated tau at PHF-1 (Ser396/404) and tau-1 (Ser198/199/202) epitopes was elevated prominently at 6, 9, and 12 h after the injection, and it was recovered to normal at 24 h. Simultaneously, the level of protein phosphatase-2A catalytic subunit (PP-2Ac) was reduced markedly as compared with control. These results imply that Hcy may induce hyperphosphorylation of tau with PP-2Ac involved mechanism.

Oxidative Stress in Vascular Dementia and Alzheimer's Disease: A Common Pathology

“…Further, cerebral ischemia, a common event in the development of VaD, has been associated with free radical production suggesting an altered oxidative stress status in this form of dementia. How AD and VaD pathologies overlap are not fully understood, however several data suggest that there are links between these two common forms of dementia, namely; the increased production of Aβ peptide during ischemic and hypoperfusive conditions in experimental models [60][61][62], the vasoconstrictive nature of the Aβ peptide [65], epidemiological data correlating vascular risk factors with AD [4], cerebrovascular disease potentiates cognitive decline in early stages of AD [70], abnormalities in CBF are evident in AD [74], and increased levels of Hcy, evident in both AD and VaD, have been shown to induce degenerative pathologies in in vitro experiments [89,101].…”

“…Interestingly, Hcy has been linked to the degenerative pathology apparent in AD, with HCy inducing tau hyperphosphorylation in the hippocampus of rodents. Additionally, a synergistic effect of Hcy and Aβ in vitro on cytosolic calcium and neuronal apoptosis has been demonstrated [89].…”

Calcium sensing receptor mediated the excessive generation of β-amyloid peptide induced by hypoxia in vivo and in vitro

“…According to our previous report [17], 30 mM Calhex 231 or 10 mM Xesto C or 6 mM GdCl 3 was injected into lateral cerebral ventricle every other day, then SD rats were treated in a hypoxic chamber at 8% O 2 /92% N 2 for 10 h/day for a month. After treatment, rats were anesthetized intraperitoneally with 7% chloral hydrate and the brains were removed for subsequent experiments.…”

“…In order to investigate the effect of hypoxia on the expression of BACE1 in hippocampus tissue, according to our previous report [17], immunohistochemistry was used to detect the expression of BACE1 in hippocampus. SD rats was assigned randomly to control, Calhex 231, Xesto C, hypoxia, Calhex 231 þ hypoxia and Xesto C þ hypoxia six group.…”

Homocysteine in Neurological Disease: A Marker or a Cause?

“…Excitotoxicity triggered by acute exposure of Hcy may result in abnormal tau phosphorylation and accumulation of phosphorylated tau in neurons [37]. Hcy-induced lipid peroxidation may also contribute to tau hyperphosphorylation [38].…”