ABSTRACT
Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
Subject(s)
Humans , Mice , Animals , Transcranial Magnetic Stimulation , Alzheimer Disease/therapy , Cognitive Dysfunction/therapy , Cognition , Sulfur , Iron , Iron-Sulfur Proteins , Mitochondrial ProteinsABSTRACT
Objective To evaluate the feasibility and safety of stent implantation in treating patients with symptomatic vertebral artery kinking.Methods Thirty-six patients with vertebral artery kinking confirmed by DSA and accorded with the stent implantation indications were chosen in our study;these patients were performed stent implantation.The stenosis and haemodynamics changes,and recent and postoperative complications were observed; Malek scale was adopted to evaluate the clinical efficacy during the 1-year follow-up.Results The success rate of stent implantation for patients with symptomatic vertebral artery kinking was 100％.The percentage of stenosis was significantly reduced from(76％±15％)to(8％±3％)after stenting(P＜0.05); the mean flow velocity of kinking lesion was obviously decreased from([45.4±22.3]cr/s)to([31.8±15.1]em/s,P＜0.05); cerebellum hematoma was noted in 1 patient subcutaneous hematoma of puncture point in 2 and femoral artery pseudoaneurysms after the stenting in 1; all these complications did not cause serious consequences.Malek scale indicated that 31 patients got 1 point,3 got 2 points,1 got 3 points,1 got 4 points and no one got 5 points; 31patients were asymptomatic during the 1-year follow-up; no significant in-stent restenosis was found.Conclusion Symptomatic vertebral artery kinking can be treated safely and effectively with stent implantation.
ABSTRACT
Objective To assess the impact of carotid artery stenosis on the cognitive function of elderly patients. Methods A total of 215 elderly patients with normal cognitive function were recruited from the out-patients and in-patients in our department. According to the severity of carotid stenosis defined by digital subtraction angiography or CT angiography, these patients were divided into 4 groups with severe (stenosis≥70%), moderate (stenosis 30%-69%), mild (stenosis 10%-29%) carotid artery stenosis or basically normal carotid artery (stenosis 0%-9%). The patients were followed up for 1 year, and Mini-mental State Examination (MMSE) was used to evaluate the cognitive function of the 4 groups of patients at the end of the follow-up. Results At the end of the one-year follow-up, 43.1% of patients with severe carotid artery stenosis exhibited cognitive impairment, a rate significantly higher than that in patients with moderate (22%) and mild (8.3%) stenosis and the patients with basically normal carotid artery (8.7%)(P<0.05). The MMSE scores of the patients with severe, moderate, and mild carotid artery stenosis and those with normal carotid artery all decreased one year after the examination to 19.85± 7.54, 22.71±5.73, 25.32±4.22, and 25.25±4.36, respectively, and the patients with severe carotid artery stenosis had the lowest score. Conclusion Carotid artery stenosis may lead to cognitive impairment in the elderly, and the risk is positively correlated to the degree of carotid artery stenosis.
ABSTRACT
Objective To study the effect of high-cholesterol diet on neuronal loss and Tau (set202)phosphorylation in a rat model of Alzheimer's disease(AD). Methods Twenty rats were randomized into high-cholesterol diet+AD group,standard diet+AD group,high-cholesterol diet+PBS group,and standard diet+PBS group.In the former two groups,amyloid-β peptide(Aβ1-40)was injected into the right dentate gyms of the hippocampus to establish experimenml AD,and PBS was injected instead in the latter two groups.Corresponding feed was administered in the 4 groups aS indicated.The hippocampal neuronal loss in the rats Was assessed using Nissel staining,and the level of Tau(ser202)phosphorylation was estimated with immunohistochemistry.Result The mts in cholesterol+AD group exhibited serious neuronal loss at the rate of 30.9%±4.6%.which was significantly higher than those in standard diet+AD group(22.7%±1.9%),cholesterol+PBS group(7.0%±1.5%),and standard diet+PBS group(5.4%±1.1%).The numbers of Tau-positive cells in the dentate gyrus in the 4 groups were 65.5± 6.2,48.8±4.8,22.5±3.1,and 12.7±1.7,respectively. Conclusion High cholesterol diet aggravates neuronal loss and enhances Tan(ser202)phosphorylation in the dentate gyrus in AD rats.